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Tire-derived fuel (TDF) is composed of shredded scrap tires . Tires may be mixed with coal or other fuels, such as wood or chemical wastes, to be burned in concrete kilns , power plants , or paper mills . An EPA test program concluded that, with the exception of zinc emissions , potential emissions from TDF are not expected to be very much different from other conventional fossil fuels, as long as combustion occurs in a well-designed, well-operated
and well-maintained combustion device. [ 1 ]
In the United States in 2017, about 43% of scrap tires (1,736,340 tons or 106 million tires) were burnt as tire-derived fuel. Cement manufacturing was the largest user of TDF, at 46%, pulp and paper manufacturing used 29% and electric utilities used 25%. Another 25% of scrap tires were used to make ground rubber, 17% were disposed of in landfills and 16% had other uses. [ 2 ]
Historically, there has not been any volume use for scrap tires other than burning that has been able to keep up with the volume of waste generated yearly. Tires produce the same energy as petroleum and approximately 25% more energy than coal. Burning tires is lower on the hierarchy of reducing waste than recycling , but it is better than placing the tire waste in a landfill or dump, where there is a possibility for uncontrolled tire fires or the harboring of disease vectors such as mosquitoes. [ 3 ] Tire Derived Fuel is an interim solution to the scrap tire waste problem. Advances in tire recycling technology [ 4 ] might one day provide a solution other than burning by reusing tire derived material in high volume applications.
Tire derived fuel is usually consumed in the form of shredded or chipped material with most of the metal wire from the tire's steel belts removed. The analytical properties of this refined material are published in TDF Produced From Scrap Tires with 96+% Wire Removed. [ 5 ]
Tires are typically composed of about 1 to 1.5% Zinc oxide , [ 6 ] which is a well known component used in the manufacture of tires and is also toxic to aquatic and plant life. The chlorine content in tires is due primarily to the chlorinated butyl rubber liner that slows the leak rate of air. The Rubber Manufacturers Association (RMA) is a very good source for compositional data and other information on tires.
The use of TDF for heat production is controversial due to the possibility for toxin production. Reportedly, polychlorinated dibenzodioxins and furans are produced during the combustion process and there is supportive evidence to suggest that this is true under some incineration conditions. Other toxins such as NOx, SOx and heavy metals are also produced, though whether these levels of toxins are higher or lower than conventional coal and oil fired incinerators is not clear. [ 7 ]
While environmental controversy surrounding use of this fuel is wide and varied, the greatest supported evidence of toxicity comes from the presence of dioxins and furans in the flue gases. Zinc has also been found to dissolve into storm water, from shredded rubber, at acutely toxic levels for aquatic life and plants. [ 8 ]
A study of dioxin and furan content [ 9 ] of stack gasses at a variety of cement mills , paper mills , boilers, and power plants conducted in the 1990s shows a wide and inconsistent variation in dioxin and furan output when fueled partially by TDF as compared to the same facilities powered by only coal. Some facilities added as little as 4% TDF and experienced as much as a 4,140% increase in dioxin and furan emissions. Other facilities added as much as 30% TDF and experienced dioxin and furan emissions increases of only as much as 58%. Still other facilities used as much as 8% TDF and experienced a decrease of as much as 83% of dioxin and furan emissions. One facility conducted four tests with two tests resulting in decreased emissions and two resulting in increased emissions. Another facility also conducted four tests and had widely varying increases in emissions. [ 1 ]
A 2004 study showed that huge polyaromatic emissions are generated from combustion of tire rubber, at a minimum, 2 orders of magnitude higher than coal alone. The study concludes with, "atmospheric contamination dramatically increases when tire rubber is used as the fuel. Other different combustion variables compared to the ones used for coal combustion should be used to avoid atmospheric contamination by toxic, mutagenic , and carcinogenic pollutants, as well as hot-gas cleaning systems and COx capture systems ." [ 10 ] | https://en.wikipedia.org/wiki/Tire-derived_fuel |
The Tire Assault Vehicle ( TAV ) was a small remote-controlled vehicle created from a scale model kit of the German World War II-era Tiger II heavy tank , used by NASA to test the tires for the Space Shuttle . [ 1 ] [ 2 ] The TAV was used to drill into the tires to damage them, something which was too risky to perform manually because of the intensity of an aircraft tire explosion. [ 2 ]
The TAV was built from a Tamiya 1/16th scale model of the Tiger II, extensively modified into a radio-controlled, video-equipped machine to drill holes in aircraft test tires that were in imminent danger of exploding because of high air pressure, high temperatures, or cord wear. [ 1 ] [ 2 ] Only roughly one quarter of the original model kit parts remained in the finished TAV, with most of the vehicle made from third-party hardware and custom-made metal parts. [ 1 ]
The TAV was used in conjunction with the Convair 990 Landing System Research Aircraft, which tested Space Shuttle tires. It was imperative to know the extreme conditions the shuttle tires could tolerate at landing without putting the shuttle and its crew at risk. In addition, the CV-990 was able to land repeatedly to test the tires. [ 2 ]
The TAV was developed by David Carrott, a Planning Research Corporation (PRC) employee under contract to NASA. [ 2 ] It survived its service as a test vehicle, and as of 2017 was on display at the NASA Armstrong Gift Shop at Edwards Air Force Base . [ 1 ]
As of 2023 [update] , Tamiya is still advertising a version of the model kit used to build the TAV. [ 1 ] [ 3 ]
This article related to the National Aeronautics and Space Administration is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Tire_Assault_Vehicle |
Tire Science and Technology is a quarterly peer-reviewed scientific journal that publishes original research and reviews on experimental, analytical, and computational aspects of tires . Since 1978, the Tire Society has published the journal. The current editor-in-chief is Michael Kaliske ( Dresden University of Technology ).
The journal was founded in 1973 and was originally published by a committee of the American Society for Testing and Materials until 1977, when the Tire Society was incorporated for the purpose of continuing the journal. [ 1 ]
Topics of interest to journal readers include adhesion, aerospace, aging, agriculture, automotive, composite materials, constitutive modeling, contact mechanics, cord mechanics, curing, design theories, durability, elastomers, finite element analysis, force and moment behavior, groove wander, heat build up, hydroplaning, impact, manufacturing, mechanics, military, noise, pavement, performance evaluation, racing, rolling resistance, snow and ice, soil, standing waves, stiffness, strength, traction, vehicle dynamics, vibration, and wear.
This article about an engineering journal is a stub . You can help Wikipedia by expanding it .
See tips for writing articles about academic journals . Further suggestions might be found on the article's talk page . | https://en.wikipedia.org/wiki/Tire_Science_and_Technology |
In vehicle dynamics , a tire model is a type of multibody simulation used to simulate the behavior of tires . In current vehicle simulator models, the tire model is the weakest and most difficult part to simulate. [ 1 ] [ 2 ]
Tire models can be classified on their accuracy and complexity, in a spectrum that goes from more simple empirical models to more complex physical models that are theoretically grounded. [ 3 ] Empirical models include Hans B. Pacejka 's Magic Formula , while physically based models include brush models (although they are still quite simplified), and more complex and detailed physical models include RMOD-K, FTire and Hankook. [ 4 ] [ 3 ] Theoretically-based models can be in turn classified from more approximative to more complex ones, going for example from the solid model, to the rigid ring model, to the flexural (elastic) ring model (like the Fiala model), and the most complex ones based on finite element methods . [ 2 ]
Brush models were very popular in the 1960s and '70s, after which Pacejka's models became widespread for many applications. [ 5 ]
Fully physics-based tire models have been typically too computational expensive to be run in realtime driving simulations. For example, to since CDTire/3D, a physics-based tire model, cannot be run in realtime, for realtime applications typically an equivalent semi-empirical "magic formula" type of model, called CDTire/Realtime, is derived from it through experiments and a regression algorithm . [ 6 ]
In 2016, a slightly less accurate version of FTire, a physics-based tire model, was adapted to be run in real time. [ 7 ] This realtime version of FTire was shown in 2018 to run on a 2,7 GHz 12 Core Intel Xeon E5 (2014, 22 nm process, about $2000), with 900 contact road/ contact patch elements, a sample frequency of 4.0 kHz including thermal and wear simulation. [ 8 ]
The typical tire model sampling rate used in automotive simulators is 1 kHz. [ 9 ] However, running at higher frequencies, like 2 kHz, might mitigate lowered numerical stability in some scenarios, and might increase the model accuracy in frequency domain above
about 250 Hz. [ 8 ] | https://en.wikipedia.org/wiki/Tire_model |
Tirur-Nilambur metro or Malappuram Metro is a proposed rapid transit system for Malappuram metropolitan area , in India. [ 1 ] In 2024, The Malappuram District Body has also examined the feasibility of implementing a metro rail project for the Malappuram metropolitan area and its suburbs. Tirur Constituency Legislator Kurukkoli Moideen has submitted an initial report on a detailed feasibility study on the feasibility of implementing the project and presented a motion in the Kerala Assembly for this purpose. [ 2 ] This was first proposed in 2012 and then in 2025. [ 3 ] [ 4 ] [ 5 ]
In 2017, Licensed Engineers & Supervisors Federation-LENSFED proposed the Tirur-Nilambur Metro Line. The project report was submitted to the government and elected representatives. The project is planned to be constructed in multiple phases from Tirur to Ponnani and from Tirur to Nilambur. The total length of the route is 80 km. Most of the route is planned to be built on elevated rail tracks above the roads. In 2025, Tirur-Nilambur metro proposal for a metro line between Tirur and Nilambur in Malappuram was presented in the assembly in 2025. Kurukkoli Moideen of the Indian Union Muslim League raised the demand through a focus group resolution. Kurukoli opined that a metro-style railway line in the densely populated Malappuram district would help save travel distance, cost and time. [ citation needed ]
In 2012, Malappuram Metro Rail is a proposed mass transit system for the city by Lensfed [ 6 ] (Licensed Engineers & Supervisors Federation). The proposal was considering the future urban scenario which would demand a transport system that can cater to the million plus population of the Malappuram urban agglomeration . In April 2012, Lensfed submitted detailed project report to Government which proposed 8 major stations and 9 intermediate stations out of which three elevated stations at Malappuram Central , Kondotty and Angadipuram . The alignment is similar to the proposed railway line of Calicut-Malappuram-Angadipuram. Apart from this, there is a proposal to extend proposed Kozhikode Light Metro Rail network to Malappuram during its third phase of expansion, paving a way to Calicut - Malappuram 'Urban Corridor' concept | https://en.wikipedia.org/wiki/Tirur-Nilambur_metro |
The Tishchenko reaction is an organic chemical reaction that involves disproportionation of an aldehyde in the presence of an alkoxide . The reaction is named after Russian organic chemist Vyacheslav Tishchenko , who discovered that aluminium alkoxides are effective catalysts for the reaction. [ 1 ] [ 2 ] [ 3 ]
In the related Cannizzaro reaction , the base is sodium hydroxide and then the oxidation product is a carboxylic acid and the reduction product is an alcohol .
The reaction involving benzaldehyde was discovered by Claisen using sodium benzylate as base. [ 1 ] The reaction produces benzyl benzoate . [ 4 ]
Enolizable aldehydes are not amenable to Claisen's conditions. Vyacheslav Tishchenko discovered that aluminium alkoxides allowed the conversion of enolizable aldehydes to esters. | https://en.wikipedia.org/wiki/Tishchenko_reaction |
Tisotumab vedotin , sold under the brand name Tivdak , is an antibody-drug conjugate used to treat cervical cancer . [ 1 ] It is a combination of tisotumab, a monoclonal antibody against tissue factor , and monomethyl auristatin E (MMAE), a potent inhibitor of cell division . It is administered by infusion into a vein . [ 1 ]
Tisotumab vedotin was approved for medical use in the United States in September 2021. [ 1 ] [ 2 ] The US Food and Drug Administration considers it to be a first-in-class medication . [ 3 ]
In the United States, Tivdak carries a boxed warning for ocular toxicity , which occurs in up to 60% of treated patients. [ 1 ] In clinical trials , the most common forms of ocular toxicity were dry eye , conjunctivitis , corneal damage, and blepharitis . [ 1 ]
Other common adverse effects include bleeding (occurring in approximately 60% of patients, most often nosebleed ) and peripheral neuropathy (42% of patients). [ 1 ] Like all drugs containing MMAE, tisotumab vedotin can cause inflammation of the lungs . [ 1 ]
The antibody portion of tisotumab vedotin (tisotumab) binds to and forms a complex with tissue factor , a molecule expressed on the surface of cancer cells. This complex is then taken up into the cell, where tisotumab vedotin is broken down by proteolytic cleavage , releasing MMAE, which stops the cell cycle and kills the cell by apoptosis . [ 1 ]
Tisotumab vedotin was developed by Genmab in Utrecht, the Netherlands , and Copenhagen, Denmark , with the code name TF-011-MMAE. [ 4 ] In September 2021, tisotumab vedotin was granted accelerated approval by United States Food and Drug Administration for the use of recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. [ 5 ]
In April 2024, tisotumab vedotin was granted traditional approval by the US Food and Drug Administration (FDA) for recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. [ 6 ] Tisotumab vedotin previously received accelerated approval for this indication. [ 6 ]
In January 2025, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Tivdak, intended for the treatment of recurrent or metastatic cervical cancer. [ 7 ] The applicant for this medicinal product is Pfizer Europe MA EEIG. [ 7 ]
Tisotumab vedotin is the international nonproprietary name . [ 8 ] Tivdak is the brand name for tisotumab vedotin in the United States. [ 2 ] | https://en.wikipedia.org/wiki/Tisotumab_vedotin |
In biology , tissue is an assembly of similar cells and their extracellular matrix from the same embryonic origin that together carry out a specific function. [ 1 ] [ 2 ] Tissues occupy a biological organizational level between cells and a complete organ . Accordingly, organs are formed by the functional grouping together of multiple tissues. [ 3 ]
The English word "tissue" derives from the French word " tissu ", the past participle of the verb tisser, "to weave".
The study of tissues is known as histology or, in connection with disease, as histopathology . Xavier Bichat is considered as the "Father of Histology". Plant histology is studied in both plant anatomy and physiology . The classical tools for studying tissues are the paraffin block in which tissue is embedded and then sectioned, the histological stain , and the optical microscope . Developments in electron microscopy , immunofluorescence , and the use of frozen tissue-sections have enhanced the detail that can be observed in tissues. With these tools, the classical appearances of tissues can be examined in health and disease , enabling considerable refinement of medical diagnosis and prognosis .
In plant anatomy , tissues are categorized broadly into three tissue systems: the epidermis , the ground tissue , and the vascular tissue .
Plant tissues can also be divided differently into two types:
Meristematic tissue consists of actively dividing cells and leads to increase in length and thickness of the plant. The primary growth of a plant occurs only in certain specific regions, such as in the tips of stems or roots. It is in these regions that meristematic tissue is present. Cells of this type of tissue are roughly spherical or polyhedral to rectangular in shape, with thin cell walls . New cells produced by meristem are initially those of meristem itself, but as the new cells grow and mature, their characteristics slowly change and they become differentiated as components of meristematic tissue, being classified as:
1.Primary meristem.
2.Secondary meristem.
The cells of meristematic tissue are similar in structure and have a thin and elastic primary cell wall made of cellulose . They are compactly arranged without inter-cellular spaces between them. Each cell contains a dense cytoplasm and a prominent cell nucleus . The dense protoplasm of meristematic cells contains very few vacuoles . Normally the meristematic cells are oval, polygonal , or rectangular in shape.
Meristematic tissue cells have a large nucleus with small or no vacuoles because they have no need to store anything. Their basic function is to multiply and increase the girth and length of the plant, with no intercellular spaces.
Permanent tissues may be defined as a group of living or dead cells formed by meristematic tissue and have lost their ability to divide and have permanently placed at fixed positions in the plant body. Meristematic tissues that take up a specific role lose the ability to divide. This process of taking up a permanent shape, size and a function is called cellular differentiation . Cells of meristematic tissue differentiate to form different types of permanent tissues. There are 2 types of permanent tissues:
Simple permanent tissue is a group of cells which are similar in origin, structure, and function. They are of three types:
Parenchyma (Greek, para – 'beside'; enchyma– infusion – 'tissue') is the bulk of a substance. In plants, it consists of relatively unspecialized living cells with thin cell walls that are usually loosely packed so that intercellular spaces are found between cells of this tissue. These are generally isodiametric, in shape. They contain small number of vacuoles or sometimes they even may not contain any vacuole. Even if they do so the vacuole is of much smaller size than of normal animal cells. This tissue provides support to plants and also stores food. Chlorenchyma is a special type of parenchyma that contains chlorophyll and performs photosynthesis. In aquatic plants, aerenchyma tissues, or large air cavities, give support to float on water by making them buoyant. Parenchyma cells called idioblasts have metabolic waste. Spindle shaped fibers are also present in this cell to support them and known as prosenchyma, succulent parenchyma also noted. In xerophytes , parenchyma tissues store water.
Collenchyma (Greek, 'Colla' means gum and 'enchyma' means infusion) is a living tissue of primary body like Parenchyma . Cells are thin-walled but possess thickening of cellulose , water and pectin substances ( pectocellulose ) at the corners where a number of cells join. This tissue gives tensile strength to the plant and the cells are compactly arranged and have very little inter-cellular spaces. It occurs chiefly in hypodermis of stems and leaves. It is absent in monocots and in roots.
Collenchymatous tissue acts as a supporting tissue in stems of young plants. It provides mechanical support, elasticity, and tensile strength to the plant body. It helps in manufacturing sugar and storing it as starch. It is present in the margin of leaves and resists tearing effect of the wind.
Sclerenchyma (Greek, Sclerous means hard and enchyma means infusion) consists of thick-walled, dead cells and protoplasm is negligible. These cells have hard and extremely thick secondary walls due to uniform distribution and high secretion of lignin and have a function of providing mechanical support. They do not have inter-cellular spaces between them. Lignin deposition is so thick that the cell walls become stronger, rigid and impermeable to water, which are also known as a stone cells or sclereids. These tissues are mainly of two types: sclerenchyma fiber and sclereids.
Sclerenchyma fiber cells have a narrow lumen and are long, narrow and unicellular. Fibers are elongated cells that are strong and flexible, often used in ropes. Sclereids have extremely thick cell walls and are brittle, and are found in nutshells and legumes.
The entire surface of the plant consists of a single layer of cells called epidermis or surface tissue. The entire surface of the plant has this outer layer of the epidermis. Hence it is also called surface tissue. Most of the epidermal cells are relatively flat. The outer and lateral walls of the cell are often thicker than the inner walls. The cells form a continuous sheet without intercellular spaces. It protects all parts of the plant. The outer epidermis is coated with a waxy thick layer called cutin which prevents loss of water. The epidermis also consists of stomata (singular:stoma) which helps in transpiration .
The complex permanent tissue consists of more than one type of cells having a common origin which work together as a unit. Complex tissues are mainly concerned with the transportation of mineral nutrients, organic solutes (food materials), and water. That's why it is also known as conducting and vascular tissue. The common types of complex permanent tissue are:
Xylem and phloem together form vascular bundles.
Xylem (Greek, xylos = wood) serves as a chief conducting tissue of vascular plants. It is responsible for the conduction of water and inorganic solutes. Xylem consists of four kinds of cells:
Xylem tissue is organised in a tube-like fashion along the main axes of stems and roots. It consists of a combination of parenchyma cells, fibers, vessels, tracheids, and ray cells. Longer tubes made up of individual cellssels tracheids, while vessel members are open at each end. Internally, there may be bars of wall material extending across the open space. These cells are joined end to end to form long tubes. Vessel members and tracheids are dead at maturity. Tracheids have thick secondary cell walls and are tapered at the ends. They do not have end openings such as the vessels. The end overlap with each other, with pairs of pits present. The pit pairs allow water to pass from cell to cell.
Though most conduction in xylem tissue is vertical, lateral conduction along the diameter of a stem is facilitated via rays. [ citation needed ] Rays are horizontal rows of long-living parenchyma cells that arise out of the vascular cambium.
Phloem consists of:
Phloem is an equally important plant tissue as it also is part of the 'plumbing system' of a plant. Primarily, phloem carries dissolved food substances throughout the plant. This conduction system is composed of sieve-tube member and companion cells, that are without secondary walls. The parent cells of the vascular cambium produce both xylem and phloem. This usually also includes fibers, parenchyma and ray cells. Sieve tubes are formed from sieve-tube members laid end to end. The end walls, unlike vessel members in xylem, do not have openings. The end walls, however, are full of small pores where cytoplasm extends from cell to cell. These porous connections are called sieve plates. In spite of the fact that their cytoplasm is actively involved in the conduction of food materials, sieve-tube members do not have nuclei at maturity. It is the companion cells that are nestled between sieve-tube members that function in some manner bringing about the conduction of food. Sieve-tube members that are alive contain a polymer called callose, a carbohydrate polymer, forming the callus pad/callus, the colourless substance that covers the sieve plate. Callose stays in solution as long as the cell contents are under pressure. Phloem transports food and materials in plants upwards and downwards as required.
Animal tissues are grouped into four basic types: connective , muscle , nervous , and epithelial . [ 4 ] Collections of tissues joined in units to serve a common function compose organs. While most animals can generally be considered to contain the four tissue types, the manifestation of these tissues can differ depending on the type of organism. For example, the origin of the cells comprising a particular tissue type may differ developmentally for different classifications of animals. Tissue appeared for the first time in the diploblasts , but modern forms only appeared in triploblasts .
The epithelium in all animals is derived from the ectoderm and endoderm (or their precursor in sponges ), with a small contribution from the mesoderm , forming the endothelium , a specialized type of epithelium that composes the vasculature . By contrast, a true epithelial tissue is present only in a single layer of cells held together via occluding junctions called tight junctions , to create a selectively permeable barrier. This tissue covers all organismal surfaces that come in contact with the external environment such as the skin , the airways, and the digestive tract. It serves functions of protection, secretion , and absorption, and is separated from other tissues below by a basal lamina .
The connective tissue and the muscular are derived from the mesoderm. The nervous tissue is derived from the ectoderm.
The epithelial tissues are formed by cells that cover the organ surfaces, such as the surface of skin , the airways , surfaces of soft organs, the reproductive tract , and the inner lining of the digestive tract . The cells comprising an epithelial layer are linked via semi-permeable, tight junctions ; hence, this tissue provides a barrier between the external environment and the organ it covers. In addition to this protective function, epithelial tissue may also be specialized to function in secretion , excretion and absorption . Epithelial tissue helps to protect organs from microorganisms, injury, and fluid loss.
Functions of epithelial tissue:
There are many kinds of epithelium, and nomenclature is somewhat variable. Most classification schemes combine a description of the cell-shape in the upper layer of the epithelium with a word denoting the number of layers: either simple (one layer of cells) or stratified (multiple layers of cells). However, other cellular features such as cilia may also be described in the classification system. Some common kinds of epithelium are listed below:
Connective tissues are made up of cells separated by non-living material, which is called an extracellular matrix . This matrix can be liquid or rigid. For example, blood contains plasma as its matrix and bone's matrix is rigid. Connective tissue gives shape to organs and holds them in place. Blood, bone, tendon, ligament, adipose, and areolar tissues are examples of connective tissues. One method of classifying connective tissues is to divide them into three types: fibrous connective tissue, skeletal connective tissue, and fluid connective tissue.
Muscle cells (myocytes) form the active contractile tissue of the body. Muscle tissue functions to produce force and cause motion, either locomotion or movement within internal organs. Muscle is formed of contractile filaments and is separated into three main types; smooth muscle , skeletal muscle and cardiac muscle . Smooth muscle has no striations when examined microscopically. It contracts slowly but maintains contractibility over a wide range of stretch lengths. It is found in such organs as sea anemone tentacles and the body wall of sea cucumbers . Skeletal muscle contracts rapidly but has a limited range of extension. It is found in the movement of appendages and jaws. Obliquely striated muscle is intermediate between the other two. The filaments are staggered and this is the type of muscle found in earthworms that can extend slowly or make rapid contractions. [ 5 ] In higher animals striated muscles occur in bundles attached to bone to provide movement and are often arranged in antagonistic sets. Smooth muscle is found in the walls of the uterus , bladder , intestines , stomach , oesophagus , respiratory airways , and blood vessels . Cardiac muscle is found only in the heart , allowing it to contract and pump blood through the body.
Cells comprising the central nervous system and peripheral nervous system are classified as nervous (or neural) tissue. In the central nervous system, neural tissues form the brain and spinal cord . In the peripheral nervous system, neural tissues form the cranial nerves and spinal nerves , inclusive of the motor neurons .
Mineralized tissues are biological tissues that incorporate minerals into soft matrices. Such tissues may be found in both plants and animals.
Xavier Bichat introduced the word tissue into the study of anatomy by 1801. [ 6 ] He was "the first to propose that tissue is a central element in human anatomy , and he considered organs as collections of often disparate tissues, rather than as entities in themselves". [ 7 ] Although he worked without a microscope , Bichat distinguished 21 types of elementary tissues from which the organs of the human body are composed, [ 8 ] a number later reduced by other authors. | https://en.wikipedia.org/wiki/Tissue_(biology) |
Tissue Engineering and Regenerative Medicine International Society is an international learned society dedicated to tissue engineering and regenerative medicine . [ 1 ]
Regenerative medicine involves processes of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function. A major technology of regenerative medicine is tissue engineering, [ 2 ] which has variously been defined as "an interdisciplinary field that applies the principles of engineering and the life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function", or "the creation of new tissue by the deliberate and controlled stimulation of selected target cells through a systematic combination of molecular and mechanical signals". [ 3 ]
Tissue engineering emerged during the 1990s as a potentially powerful option for regenerating tissue and research initiatives were established in various cities in the US and in European countries including the UK, Italy, Germany and Switzerland, and also in Japan. Soon fledgling societies were formed in these countries in order to represent these new sciences, notably the European Tissue Engineering Society (ETES) and, in the US, the Tissue Engineering Society (TES), soon to become the Tissue Engineering Society international (TESi) and the Regenerative Medicine Society (RMS). [ 4 ]
Because of the overlap between the activities of these societies and the increasing globalization of science and medicine, considerations of a merger between TESI and ETES and RMS were initiated in 2004 and agreement was reached during 2005 about the formation of the consolidated society, the Tissue Engineering and Regenerative Medicine International Society (TERMIS). [ 5 ] Election of officers for TERMIS took place in September 2005, and the by-laws were approved by the Board.
Rapid progress in the organization of TERMIS took place during late 2005 and 2006. The SYIS, Student and Young Investigator Section was established in January 2006, website and newsletter launched and membership dues procedures put in place.
It was determined that each Chapter would have its own Council, the overall activities being determined by the Governing Board, on which each Council was represented, and an executive committee.
At the beginning of the Society, it was agreed that there would be Continental Chapters of TERMIS, initially TERMIS-North America (TERMIS-NA) and TERMIS-Europe (TERMIS-EU), to be joined at the time of the major Shanghai conference in October 2005 by TERMIS-Asia Pacific (TERMIS-AP). It was subsequently agreed that the remit of TERMIS-North America should be expanded to incorporate activity in South America, the chapter becoming TERMIS-Americas (TERMS-AM) officially in 2012.
The Student and Young Investigator Section of TERMIS (TERMIS-SYIS) brings together undergraduate and graduate students, post-doctoral researchers and young investigators in industry and academia related to tissue engineering and regenerative medicine. [ 6 ] It follows the organizational and working pattern of TERMIS.
A contract was signed between TERMIS and the Mary Ann Liebert publisher which designated the journal Tissue Engineering , Parts A, B, and C as the official journal of TERMIS with free on-line access for the membership. [ 7 ]
It was agreed that there would be a World Congress every three years, with each Chapter organizing its own conference in the intervening two years.
Each TERMIS chapter has defined awards to recognize outstanding scientists and their contributions within the community.
Fellows of Tissue Engineering and Regenerative Medicine (FTERM) recipients are: [ 8 ]
Emeritus
Deceased Fellows | https://en.wikipedia.org/wiki/Tissue_Engineering_and_Regenerative_Medicine_International_Society |
Tissue clearing refers to a group of chemical techniques used to turn tissues transparent. [ 1 ] [ 2 ] [ 3 ] By turning tissues transparent to certain wavelengths of light, it allows one to gain optical access to a tissue. [ 1 ] That is, light can pass into and out of the cleared tissue freely, allowing one to see the structures deep within the tissue without physically cutting it open. Many tissue clearing methods exist, each with different strengths and weaknesses. [ 2 ] [ 4 ] Some are generally applicable, while others are designed for specific applications. [ 4 ] Tissue clearing is usually useful only combined with one or more fluorescent labeling techniques such as immunolabeling and subsequently imaged, most often by optical sectioning microscopy techniques. [ 1 ] [ 5 ] [ 6 ] Tissue clearing has been applied to many areas in biological research. [ 7 ] It is one of the more efficient ways to perform three-dimensional histology .
In the early 1900s, Werner Spalteholz developed a technique that allowed the clarification of large tissues, [ 2 ] [ 8 ] using Wintergrünöl ( methyl salicylate ) and benzyl benzoate . [ 9 ] Various scientists then introduced their own variations on Spalteholz's technique. [ 8 ] Tuchin et al. introduced tissue optical clearing (TOC) in 1997, adding a new branch of tissue clearing that was hydrophilic instead of hydrophobic like Spalteholz's technique. [ 1 ] [ 10 ] In the 1980s, Andrew Murray & Marc Kirschner developed a two-step process, wherein tissues were first dehydrated with alcohol and subsequently made transparent by immersion in a mixture of benzyl alcohol and benzyl benzoate (BABB), a technique they coupled with light sheet fluorescence microscopy , [ 11 ] [ 2 ] [ 3 ] which remains the method with the highest clearing efficacy to date, regardless any tissue pre-processing step. [ 12 ] In the most extreme case, it allows the clearing of a whole mouse of even a whole human brain . [ 13 ]
Tissue opacity is thought to be the result of light scattering due to heterogeneous refractive indices . [ 1 ] [ 4 ] [ 5 ] Tissue clearing methods chemically homogenize refractive indices, resulting in almost completely transparent tissue. [ 4 ] [ 6 ]
While there are multiple class names for tissue-clearing methods, they are all classified based on the final state of the tissue by the end of the clearing method. [ 1 ] These include hydrophobic clearing methods, [ 1 ] [ 2 ] [ 6 ] which may also be known as organic, [ 3 ] solvent-based, [ 4 ] [ 5 ] organic solvent-based, [ 14 ] [ 15 ] or dehydration [ 16 ] clearing methods; hydrophilic clearing methods, [ 1 ] [ 2 ] [ 6 ] which may also be known as aqueous-based [ 5 ] [ 14 ] or water-based [ 16 ] methods, and hydrogel-based clearing methods. [ 2 ] [ 1 ]
Tissue clearing methods have varying compatibility with different methods of fluorescent labeling . [ 1 ] [ 5 ] [ 6 ] Some are better suited to genetic labelling by endogenously expressed fluorescent protein , [ 1 ] [ 5 ] while others externally delivered probes as immunolabeling and chemical dye labeling. [ 1 ] [ 5 ] The latter is more general and applicable to all tissues, notably human tissues, but the penetration of the probes becomes a critical problem. [ 17 ]
After clearing and labeling, tissues are typically imaged using confocal microscopy , [ 14 ] [ 15 ] [ 16 ] two-photon microscopy , [ 1 ] [ 5 ] [ 14 ] or one of the many variants of light-sheet fluorescence microscopy . [ 7 ] [ 14 ] [ 15 ] Other less commonly used methods include optical projection tomography [ 1 ] [ 5 ] and stimulated Raman scattering . [ 5 ] [ 7 ] [ 14 ] As long as the tissue allows for the unobstructed passing of light, the optical resolution is fundamentally limited by Abbe diffraction limit . The compatibility of any tissue clearing method with any microscopy system is, therefore, configurational rather than optical.
Tissue clearing is one of the more efficient ways to facilitate 3D imaging of tissues, and hence generates massive volumes of complex data, which requires powerful computational hardware and software to store, process, analyze, and visualize. [ 1 ] [ 6 ] [ 16 ] A single mouse brain can generate terabytes of data. [ 2 ] [ 6 ] [ 16 ] Both commercial and open-source software exists to address this need, some of it adapted from solutions for two-dimensional images and some of it designed specifically for the three-dimensional images produced by imaging of cleared tissues. [ 1 ] [ 14 ] [ 15 ]
Tissue clearing has been applied to the nervous system, [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 14 ] [ 18 ] [ 19 ] bones (including teeth), [ 7 ] [ 14 ] [ 15 ] [ 20 ] [ 21 ] [ 22 ] skeletal muscles, [ 7 ] [ 22 ] [ 23 ] hearts and vasculature, [ 7 ] [ 14 ] [ 24 ] gastrointestinal organs, [ 7 ] [ 25 ] urogenital organs, [ 7 ] [ 14 ] [ 26 ] skin, [ 7 ] [ 27 ] lymph nodes, [ 7 ] mammary glands, [ 7 ] lungs, [ 7 ] eyes, [ 7 ] tumors, [ 7 ] [ 14 ] and adipose tissues. [ 7 ] [ 14 ] Whole-body clearing is less common, but has been done in smaller animals, including rodents. [ 1 ] [ 6 ] [ 7 ] Tissue clearing has also been applied to human cancer tissues. [ 28 ] [ 29 ] For some techniques, bone tissue must be decalcified to remove light-scattering hydroxyapatite crystals, leaving behind a protein matrix suitable for clearing. [ 30 ] [ 31 ] | https://en.wikipedia.org/wiki/Tissue_clearing |
Tissue culture is the growth of tissues or cells in an artificial medium separate from the parent organism. This technique is also called micropropagation . This is typically facilitated via use of a liquid, semi-solid, or solid growth medium , such as broth or agar . Tissue culture commonly refers to the culture of animal cells and tissues, with the more specific term plant tissue culture being used for plants. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows . [ 1 ]
In 1885 Wilhelm Roux removed a section of the medullary plate of an embryonic chicken and maintained it in a warm saline solution for several days, establishing the basic principle of tissue culture. In 1907 the zoologist Ross Granville Harrison demonstrated the growth of frog embryonic cells that would give rise to nerve cells in a medium of clotted lymph . In 1913, E. Steinhardt, C. Israeli, and R. A. Lambert grew vaccinia virus in fragments of guinea pig corneal tissue. [ 2 ] In 1996, the first use of regenerative tissue was used to replace a small length of urethra, which led to the understanding that the technique of obtaining samples of tissue, growing it outside the body without a scaffold, and reapplying it, can be used for only small distances of less than 1 cm. [ 3 ]
Gottlieb Haberlandt first pointed out the possibilities of the culture of isolated tissues, plant tissue culture . [ 4 ] He suggested that the potentialities of individual cells via tissue culture as well as that the reciprocal influences of tissues on one another could be determined by this method. Since Haberlandt's original assertions, methods for tissue and cell culture have been realized, leading to significant discoveries in biology and medicine. His original idea, presented in 1902, was called totipotentiality: "Theoretically all plant cells are able to give rise to a complete plant." [ 5 ] [ 6 ] [ 7 ]
In modern usage, "Tissue culture" generally refers to the growth of cells from a multicellular organism in vitro . These cells may be cells isolated from a donor organism ( primary cells ) or an immortalised cell line . The cells are bathed in a culture medium, which contains essential nutrients and energy sources necessary for the cells' survival. [ 8 ] Thus, in its broader sense, "tissue culture" is often used interchangeably with " cell culture ". On the other hand, the strict meaning of "tissue culture" refers to the culturing of tissue pieces, i.e. explant culture .
Tissue culture is an important tool for the study of the biology of cells from multicellular organisms. It provides an in vitro model of the tissue in a well defined environment which can be easily manipulated and analysed. In animal tissue culture, cells may be grown as two-dimensional monolayers (conventional culture) or within fibrous scaffolds or gels to attain more naturalistic three-dimensional tissue-like structures (3D culture). Eric Simon, in a 1988 NIH SBIR grant report, showed that electrospinning could be used to produce nano- and submicron-scale polymeric fibrous scaffolds specifically intended for use as in vitro cell and tissue substrates. This early use of electrospun fibrous lattices for cell culture and tissue engineering showed that various cell types would adhere to and proliferate upon polycarbonate fibers. It was noted that as opposed to the flattened morphology typically seen in 2D culture, cells grown on the electrospun fibers exhibited a more rounded 3-dimensional morphology generally observed of tissues in vivo . [ 9 ]
Plant tissue culture in particular is concerned with the growing of entire plants from small pieces of plant tissue, cultured in medium. [ 10 ] The technique of plant tissue culture, i.e., culturing plant cells or tissues in artificial medium supplemented with required nutrients, has many applications in efficient clonal propagation (true to the type or similar) which may be difficult via conventional breeding methods. Tissue culture is used in creating genetically modified plants , as it allows scientists to introduce DNA changes to plant tissue via Agrobacterium tumefaciens or a gene gun and then generate a full plant from these modified cells. [ 11 ]
Tissue cultures are commonly used in plant propagation . [ 12 ] [ 13 ] The advantage of such vegetative propagation is that it obtains a large amount of homogeneous material, which is of great importance in the propagation of valuable cultivars of ornamental plants, [ 13 ] and rootstocks for fruit trees. In addition, fruit plants or flowers can be obtained free of viruses , phytoplasmas , viroids . [ 14 ]
Because plant cells are totipotent, adding growth hormones to the media can trigger the callus cells to develop roots, shoots and entire plants. [ 15 ]
There are three common methods to establish cell culture from animals. The first is organ culture where whole organs from embryos or partial adult organs are used to initiate the organ culture in vitro . These cells retain their differentiated character and functional activity in organ culture. The second method is primary explant culture, in which fragments derived from animal tissue are attached to a surface using an extracellular matrix component (ECM), such as collagen or a plasma clot. This culture is known as a primary explant, and migrating cells are known as outgrowth. This has been used to analyze the growth characteristics of cancer cells in comparison to their normal counterparts. [ 16 ] The third method is cell culture, of which there are three types: (1) precursor cell culture, i.e. undifferentiated cells that are to be differentiate, (2) differentiated cell culture, i.e. completely differentiated cells that have lost the capacity to further differentiate, and (3) stem cell culture, i.e. undifferentiated cells that can develop into any kind of cell." [ 16 ]
Animal cell culture is used for many research purposes and commercial business also as:
A cell line can be defined as a permanently established cell culture which will propagate forever. Investigators mostly get cell lines from other investigators or from cell banks (such as the American Type Culture Collection), because its much easier than creating new one. In special cases, investigators are obligated to establish a cell line. To do this you must use one of the following cells:
Transformed cell lines, Tumor tissue or Transforming normal cell in vitro [ 17 ]
Subculture is the transfer of cells from one culture to start a new one. During this process the proliferating cells are subdivided, to form new cell lines. [ 18 ]
The most advanced tissue culture science is now focused on stem cells, stem cells can be used for tissue replacement or either organs. stem cell is a primitive type of cell which has the ability to differentiate to all the 220 cell types found in human body. Stem cells can be obtained from blood, brain, or muscle tissue but the most important one is from early embryos which has the capability to differentiate to any other cell. [ 17 ] | https://en.wikipedia.org/wiki/Tissue_culture |
Tissue image cytometry or tissue cytometry is a method of digital histopathology and combines classical digital pathology (glass slides scanning and virtual slide generation) and computational pathology (digital analysis) into one integrated approach with solutions for all kinds of diseases, tissue and cell types as well as molecular markers and corresponding staining methods to visualize these markers. Tissue cytometry uses virtual slides as they can be generated by multiple, commercially available slide scanners, as well as dedicated image analysis software – preferentially including machine and deep learning algorithms. [ 1 ] Tissue cytometry enables cellular analysis within thick tissues, retaining morphological and contextual information, including spatial information on defined cellular subpopulations. [ 2 ]
In this process, a tissue sample, either formalin -fixed paraffin -embedded (FFPE) or frozen tissue section, also referred to as “cryocut”, is labelled with either immunohistochemistry [ 3 ] (IHC) or immunofluorescent markers, scanned with high-throughput slide scanners and the data gathered from virtual slides is processed and analyzed using software that is able to identify individual cells in tissue context automatically and distinguish between nucleus and cytoplasm for each cell. [ 1 ] Additional algorithms can identify cellular membranes, subcellular structures (like cytoskeletal fibers, vacuoles , nucleoli) and/or multicellular tissue structures (glands, glomeruli , epidermis , or tumor foci). [ 4 ] Fluorescence Activated Cell Sorting (FACS) is a method of analysis that measures fluorescence signals on single cells, where the signal comes from antibody-mediated staining techniques and phenotypes detected by flow cytometry . [ 5 ] The major limitation of flow cytometry is that it can only be applied – as the name suggest – to cells in solution. Although methods of “solubilizing” solid tissue exist, any such processing irrevocably destroys the tissue architecture and any spatial context. Hence, tissue cytometry complements the use of flow cytometry and fluorescence microscope [ 6 ] in basic research, clinical practice, and clinical trials by providing FACS-like analyses on solid tissue sections (as well as adherent cell cultures) in situ. The advantage of tissue cytometry against flow cytometry is that tissue cytometry does not require the cells to be suspended in fluid, aiding in maintaining the integrity of the tissue structure, morphology, and contextual information, further assisting in precise and accurate contextual analysis that are not possible in flow cytometry.
Immunohistochemistry is used in clinical practice, where tissue biopsies from every potential cancer patient are collected, fixed in formalin and embedded on paraffin. These tissue sections are serially cut in a microtome to provide thin sections, representing the diagnostic material for clinical diagnoses. [ 3 ] Once stained initially with hematoxylin and eosin stain to detect cancer cells. Multiple marker staining is performed for proliferation, lineage, prognostic and oncogenic targets. Pathologists used optical microscope for the evaluation through the objective lenses and conclude the diagnosis by scoring the staining in percentage or as positive/negative. Visual evaluation provides a subjective diagnosis and plan of treatment.
By converting glass slides into digital images, digital pathology changed how pathologists interacted with tissue specimens. However, the initial phase of digital pathology primarily focused on image viewing and sharing. While this enabled remote consultations and facilitated image archiving, it did not fundamentally alter the core process of pathology: the manual interpretation of tissue morphology by human experts.
A more robust and automated system was designed to perform flow cytometry-like analyses on immunostained cells in a fixed tissue and termed tissue cytometry. [ 7 ] The technique was introduced in the 1990s based on patents by Steiner and Ecker, [ 8 ] describing a procedure for “Cytometric Analysis of Diverse Cell Populations in Tissue Sections or Cell Culture Visualized Through Fluorescence Dyes and/or Chromogens". Tissue cytometry emerged as a transformative extension of digital pathology, promising to bridge the gap between image-based analysis and quantitative, data-driven insights. At its core, tissue cytometry enables the automated and quantitative analysis of cellular and tissue features. By employing computational algorithms and machine learning models, it can accurately segment nuclei, identify cell types, and quantify protein expression levels within the tissue context.
Additional patents were filed in the early 21st century by Hernani et al. to perform virtual flow cytometry on immunostained tissue. [ 9 ] The latter's basics were derived from the procedure presented in 1982 by Gillete et al., describing the qualitative analysis of spectral mixtures by using factor analysis in conjunction with a spectral reference library. [ 10 ] Following this study, Zhou R et al. published a method to quantify prostate-specific acid phosphatase (PSAP) in histologic sections of prostate tumor with the peroxidase-antiperoxidase (PAP) complex technique using diaminobenzidine (DAB) as a substrate. [ 11 ]
The integration of AI and machine learning has been instrumental in the development of tissue cytometry. For instance, AI-driven algorithms can be trained to identify specific cell types, detect subtle morphological changes associated with disease, or quantify the density of immune cells within a tumor microenvironment. [ 12 ]
By precisely delineating individual nuclei, researchers can extract valuable information about nuclear size, shape, and texture, which can be correlated with various pathological conditions. Similarly, tissue segmentation algorithms enable the identification of different tissue compartments, such as tumor, stroma, and immune infiltrate, facilitating the analysis of spatial relationships between cellular components. [ 13 ]
Modern tissue cytometers can analyze many thousands of cells within the tissue sample in "real time".
A tissue cytometer has 2 main components: (I) a high-throughput scanner to acquire the high-quality virtual image of immunohistochemical and/or fluorescent marker labelled tissue sections, (II) software for image analysis and data interpretation.
Tumor Microenvironment: Tissue cytometry is heavily used in research to characterize the tumor microenvironment including e.g. identification of the immune landscape or tumor-vascularization, within IHC/IF-processed tissue sections. One reason is that by using this technology the complex tissue architecture stays intact and therefore also spatial relationships between cellular phenotypes and/or multicellular structures can be analyzed. [ 14 ]
By utilizing tissue cytometry multiple research groups were able to demonstrate the impact of various immune cell subpopulations (CD4, CD68, CD8, CD20, Foxp3, PD1) on patient survival in different cancer types (e.g. breast cancer, colon cancer, gastric cancer, melanoma, non-small cell lung cancer). [ 14 ] Since in cancer therapy a novel treatment strategy is targeting immune checkpoints (molecules that inhibit the antitumoral immune reaction), the insights gained by tissue cytometry may help to find new target molecules/biomarkers as well as to determine the best treatment strategy for patients. [ 14 ]
Immunology: Immune cell context is important for delineating the etymology of inflammatory diseases, which often result from impaired function of adaptive and/or innate immune cells. Tissue cytometry is useful for detecting and localizing specific cells, especially heterogeneous populations, within their native tissue environment and identifying the cues behind the disease. [ 15 ] For example, it was used to investigate IgG4-related diseases: one paper reports about fibrosing mediastinitis being driven by CD4+ CTLs rather than Th2 cells where infiltration of CD4+ CTLs was illustrated by tissue cytometry. [ 16 ] Follow-up studies investigated how follicular T cells influence B-cell class-switching events in IgG4-related disease and Kimura disease – researchers found a correlation between AICDA+CD19+ B cells and IgG4 expression using tissue cytometry. [ 17 ]
Mesenchymal Stem Cells Characterization : Mesenchymal stem cells (MSCs) are multipotent cells that have the capacity differentiate into several sub-types such as bone, cartilage, muscle, developing teeth and fat tissue which has clinical importance for regenerative medicine. [ 18 ] However, although there are defined minimal phenotypic criteria, MSCs due to their heterogeneous nature need to be further characterized regarding their distinct biomarkers. [ 19 ] Tissue cytometry promisingly assists to describe the biomarkers of quiescent MCSs and furthermore characterize the effect of hyaluronan on this population. [ 20 ] Tissue cytometry can also used to investigate MSCs interaction with glioblastoma: to characterize cell fusion, extracellular vesicle transfer and intercellular communications. [ 21 ] Additionally, tissue cytometry is utilized to image the murine hippocampus and visualize M1/M2 microglia in mice with MSCs transplantation as a model for Alzheimer’s disease. [ 22 ]
COVID-19: COVID-19 pandemic required various tools to outline the disease progression and severity. Using tissue cytometry, researchers reported about interplay of immune cells and SARS-CoV-2 virus and its effect on disease: for instance, one study showed that CD4+ cytotoxic T cells expanded significantly in the lungs in severe COVID-19. [ 23 ] Another finding illustrates loss of germinal centers in lymph nodes and spleens in acute COVID-19, which was shown by multi-color immunofluorescence cytometry. [ 24 ]
Neuroscience: Tracking neurodevelopmental processes is an active field of research in neuroscience. Quantitative tissue analysis is widely employed in the field to determine the role of different stimuli in the nervous system. [ 25 ] [ 26 ] [ 27 ] [ 28 ] A research group reported about the effect of the magnetic field on neural differentiation of pluripotent stem cells, where the phenotypic effects were observed using tissue cytometry. [ 25 ] Another application of tissue cytometry in neuroscience was shown in a study designed to evaluate the effect of stress on hypothalamic neurons. [ 26 ] | https://en.wikipedia.org/wiki/Tissue_cytometry |
Tissue engineering is a biomedical engineering discipline that uses a combination of cells , engineering , materials methods, and suitable biochemical and physicochemical factors to restore, maintain, improve, or replace different types of biological tissues. Tissue engineering often involves the use of cells placed on tissue scaffolds in the formation of new viable tissue for a medical purpose, but is not limited to applications involving cells and tissue scaffolds. While it was once categorized as a sub-field of biomaterials , having grown in scope and importance, it can be considered as a field of its own. [ 1 ]
While most definitions of tissue engineering cover a broad range of applications, in practice, the term is closely associated with applications that repair or replace portions of or whole tissues (i.e. organs , bone , cartilage , [ 2 ] blood vessels , bladder , skin , muscle etc.). Often, the tissues involved require certain mechanical and structural properties for proper functioning. The term has also been applied to efforts to perform specific biochemical functions using cells within an artificially-created support system (e.g. an artificial pancreas , or a bio artificial liver ). The term regenerative medicine is often used synonymously with tissue engineering, although those involved in regenerative medicine place more emphasis on the use of stem cells or progenitor cells to produce tissues.
A commonly applied definition of tissue engineering, as stated by Langer [ 3 ] and Vacanti, [ 4 ] is "an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve [Biological tissue] function or a whole organ". [ 5 ] In addition, Langer and Vacanti also state that there are three main types of tissue engineering: cells, tissue-inducing substances, and a cells + matrix approach (often referred to as a scaffold). Tissue engineering has also been defined as "understanding the principles of tissue growth, and applying this to produce functional replacement tissue for clinical use". [ 6 ] A further description goes on to say that an "underlying supposition of tissue engineering is that the employment of natural biology of the system will allow for greater success in developing therapeutic strategies aimed at the replacement, repair, maintenance, or enhancement of tissue function". [ 6 ]
Developments in the multidisciplinary field of tissue engineering have yielded a novel set of tissue replacement parts and implementation strategies. Scientific advances in biomaterials , stem cells, growth and differentiation factors, and biomimetic environments have created unique opportunities to fabricate or improve existing tissues in the laboratory from combinations of engineered extracellular matrices ("scaffolds"), cells, and biologically active molecules. Among the major challenges now facing tissue engineering is the need for more complex functionality, biomechanical stability, and vascularization in laboratory-grown tissues destined for transplantation. [ 7 ]
The historical origin of the term is unclear as the definition of the word has changed throughout the past few decades. The term first appeared in a 1984 publication that described the organization of an endothelium-like membrane on the surface of a long-implanted, synthetic ophthalmic prosthesis. [ 8 ]
The first modern use of the term as recognized today was in 1985 by the researcher, physiologist and bioengineer Yuan-Cheng Fung of the Engineering Research Center. He proposed the joining of the terms tissue (in reference to the fundamental relationship between cells and organs) and engineering (in reference to the field of modification of said tissues). The term was officially adopted in 1987. [ 8 ]
A rudimentary understanding of the inner workings of human tissues may date back further than most would expect. As early as the Neolithic period, sutures were being used to close wounds and aid in healing. Later on, societies such as ancient Egypt developed better materials for sewing up wounds such as linen sutures. Around 2500 BC in ancient India, skin grafts were developed by cutting skin from the buttock and suturing it to wound sites in the ear, nose, or lips. Ancient Egyptians often would graft skin from corpses onto living humans and even attempted to use honey as a type of antibiotic and grease as a protective barrier to prevent infection. In the 1st and 2nd centuries AD, Gallo-Romans developed wrought iron implants and dental implants could be found in ancient Mayans.
While these ancient societies had developed techniques that were way ahead of their time, they still lacked a mechanistic understanding of how the body was reacting to these procedures. This mechanistic approach came along in tandem with the development of the empirical method of science pioneered by René Descartes. Sir Isaac Newton began to describe the body as a "physiochemical machine" and postured that disease was a breakdown in the machine.
In the 17th century, Robert Hooke discovered the cell and a letter from Benedict de Spinoza brought forward the idea of the homeostasis between the dynamic processes in the body. Hydra experiments performed by Abraham Trembley in the 18th century began to delve into the regenerative capabilities of cells. During the 19th century, a better understanding of how different metals reacted with the body led to the development of better sutures and a shift towards screw and plate implants in bone fixation. Further, it was first hypothesized in the mid-1800s that cell-environment interactions and cell proliferation were vital for tissue regeneration.
As time progresses and technology advances, there is a constant need for change in the approach researchers take in their studies. Tissue engineering has continued to evolve over centuries. In the beginning people used to look at and use samples directly from human or animal cadavers. Now, tissue engineers have the ability to remake many of the tissues in the body through the use of modern techniques such as microfabrication and three-dimensional bioprinting in conjunction with native tissue cells/stem cells. These advances have allowed researchers to generate new tissues in a much more efficient manner. For example, these techniques allow for more personalization which allow for better biocompatibility, decreased immune response, cellular integration, and longevity. There is no doubt that these techniques will continue to evolve, as we have continued to see microfabrication and bioprinting evolve over the past decade.
In 1960, Wichterle and Lim were the first to publish experiments on hydrogels for biomedical applications by using them in contact lens construction. Work on the field developed slowly over the next two decades, but later found traction when hydrogels were repurposed for drug delivery. In 1984, Charles Hull developed bioprinting by converting a Hewlett-Packard inkjet printer into a device capable of depositing cells in 2-D. Three dimensional (3-D) printing is a type of additive manufacturing which has since found various applications in medical engineering, due to its high precision and efficiency. With biologist James Thompson's development of first human stem cell lines in 1998 followed by transplantation of first laboratory-grown internal organs in 1999 and creation of the first bioprinter in 2003 by the University of Missouri when they printed spheroids without the need of scaffolds, 3-D bioprinting became more conventionally used in medical field than ever before. So far, scientists have been able to print mini organoids and organs-on-chips that have rendered practical insights into the functions of a human body. Pharmaceutical companies are using these models to test drugs before moving on to animal studies. However, a fully functional and structurally similar organ has not been printed yet. A team at University of Utah has reportedly printed ears and successfully transplanted those onto children born with defects that left their ears partially developed.
Today hydrogels are considered the preferred choice of bio-inks for 3-D bioprinting since they mimic cells' natural ECM while also containing strong mechanical properties capable of sustaining 3-D structures. Furthermore, hydrogels in conjunction with 3-D bioprinting allow researchers to produce different scaffolds which can be used to form new tissues or organs. 3-D printed tissues still face many challenges such as adding vasculature. Meanwhile, 3-D printing parts of tissues definitely will improve our understanding of the human body, thus accelerating both basic and clinical research.
As defined by Langer and Vacanti, [ 5 ] examples of tissue engineering fall into one or more of three categories: "just cells," "cells and scaffold," or "tissue-inducing factors."
Cells are one of the main components for the success of tissue engineering approaches. Tissue engineering uses cells as strategies for creation/replacement of new tissue. Examples include fibroblasts used for skin repair or renewal, [ 23 ] chondrocytes used for cartilage repair (MACI–FDA approved product), and hepatocytes used in liver support systems
Cells can be used alone or with support matrices for tissue engineering applications. An adequate environment for promoting cell growth, differentiation, and integration with the existing tissue is a critical factor for cell-based building blocks. [ 24 ] Manipulation of any of these cell processes create alternative avenues for the development of new tissue (e.g., cell reprogramming - somatic cells, vascularization). [ citation needed ]
Techniques for cell isolation depend on the cell source. Centrifugation and apheresis are techniques used for extracting cells from biofluids (e.g., blood). Whereas digestion processes, typically using enzymes to remove the extracellular matrix (ECM), are required prior to centrifugation or apheresis techniques to extract cells from tissues/organs. Trypsin and collagenase are the most common enzymes used for tissue digestion. While trypsin is temperature dependent, collagenase is less sensitive to changes in temperature. [ citation needed ]
Primary cells are those directly isolated from host tissue. These cells provide an ex-vivo model of cell behavior without any genetic, epigenetic, or developmental changes; making them a closer replication of in-vivo conditions than cells derived from other methods. [ 25 ] This constraint however, can also make studying them difficult. These are mature cells, often terminally differentiated, meaning that for many cell types proliferation is difficult or impossible. Additionally, the microenvironments these cells exist in are highly specialized, often making replication of these conditions difficult. [ 26 ]
Secondary cells A portion of cells from a primary culture is moved to a new repository/vessel to continue being cultured. Medium from the primary culture is removed, the cells that are desired to be transferred are obtained, and then cultured in a new vessel with fresh growth medium. [ 27 ] A secondary cell culture is useful in order to ensure that cells have both the room and nutrients that they require to grow. Secondary cultures are most notably used in any scenario in which a larger quantity of cells than can be found in the primary culture is desired. Secondary cells share the constraints of primary cells (see above) but have an added risk of contamination when transferring to a new vessel. [ citation needed ]
Autologous: The donor and the recipient of the cells are the same individual. Cells are harvested, cultured or stored, and then reintroduced to the host. As a result of the host's own cells being reintroduced, an antigenic response is not elicited. The body's immune system recognizes these re-implanted cells as its own, and does not target them for attack. Autologous cell dependence on host cell health and donor site morbidity may be deterrents to their use. Adipose-derived and bone marrow-derived mesenchymal stem cells are commonly autologous in nature, and can be used in a myriad of ways, from helping repair skeletal tissue to replenishing beta cells in diabetic patients. [ 28 ] [ 29 ] [ 30 ] [ 31 ]
Allogenic: Cells are obtained from the body of a donor of the same species as the recipient. While there are some ethical constraints to the use of human cells for in vitro studies (i.e. human brain tissue chimera development [ 32 ] ), the employment of dermal fibroblasts from human foreskin demonstrates an immunologically safe and thus a viable choice for allogenic tissue engineering of the skin.
Xenogenic: These cells are derived isolated cells from alternate species from the recipient. A notable example of xenogeneic tissue utilization is cardiovascular implant construction via animal cells. Chimeric human-animal farming raises ethical concerns around the potential for improved consciousness from implanting human organs in animals. [ 33 ]
Syngeneic or isogenic: These cells describe those borne from identical genetic code. This imparts an immunologic benefit similar to autologous cell lines (see above). [ 34 ] Autologous cells can be considered syngenic, but the classification also extends to non-autologously derived cells such as those from an identical twin, from genetically identical (cloned) research models, or induced stem cells (iSC) [ 35 ] as related to the donor.
Stem cells are undifferentiated cells with the ability to divide in culture and give rise to different forms of specialized cells. Stem cells are divided into "adult" and "embryonic" stem cells according to their source. While there is still a large ethical debate related to the use of embryonic stem cells, it is thought that another alternative source – induced pluripotent stem cells – may be useful for the repair of diseased or damaged tissues, or may be used to grow new organs.
Totipotent cells are stem cells which can divide into further stem cells or differentiate into any cell type in the body, including extra-embryonic tissue.
Pluripotent cells are stem cells which can differentiate into any cell type in the body except extra-embryonic tissue. induced pluripotent stem cells (iPSCs) are subclass of pluripotent stem cells resembling embryonic stem cells (ESCs) that have been derived from adult differentiated cells. iPSCs are created by altering the expression of transcriptional factors in adult cells until they become like embryonic stem cells.
Multipotent stem cells can be differentiated into any cell within the same class, such as blood or bone . A common example of multipotent cells is Mesenchymal stem cells (MSCs).
Scaffolds are materials that have been engineered to cause desirable cellular interactions to contribute to the formation of new functional tissues for medical purposes. Cells are often 'seeded' into these structures capable of supporting three-dimensional tissue formation. Scaffolds mimic the extracellular matrix of the native tissue, recapitulating the in vivo milieu and allowing cells to influence their own microenvironments. They usually serve at least one of the following purposes: allowing cell attachment and migration, delivering and retaining cells and biochemical factors, enabling diffusion of vital cell nutrients and expressed products, and exerting certain mechanical and biological influences to modify the behaviour of the cell phase. [ citation needed ]
In 2009, an interdisciplinary team led by the thoracic surgeon Thorsten Walles implanted the first bioartificial transplant that provides an innate vascular network for post-transplant graft supply successfully into a patient awaiting tracheal reconstruction. [ 36 ]
To achieve the goal of tissue reconstruction, scaffolds must meet some specific requirements. High porosity and adequate pore size are necessary to facilitate cell seeding and diffusion throughout the whole structure of both cells and nutrients. Biodegradability is often an essential factor since scaffolds should preferably be absorbed by the surrounding tissues without the necessity of surgical removal. The rate at which degradation occurs has to coincide as much as possible with the rate of tissue formation: this means that while cells are fabricating their own natural matrix structure around themselves, the scaffold is able to provide structural integrity within the body and eventually it will break down leaving the newly formed tissue which will take over the mechanical load. Injectability is also important for clinical uses.
Recent research on organ printing is showing how crucial a good control of the 3D environment is to ensure reproducibility of experiments and offer better results. [ citation needed ]
Material selection is an essential aspect of producing a scaffold. The materials utilized can be natural or synthetic and can be biodegradable or non-biodegradable. Additionally, they must be biocompatible, meaning that they do not cause any adverse effects to cells. [ 38 ] Silicone, for example, is a synthetic, non-biodegradable material commonly used as a drug delivery material, [ 39 ] [ 40 ] while gelatin is a biodegradable, natural material commonly used in cell-culture scaffolds [ 41 ] [ 42 ] [ 43 ]
The material needed for each application is different, and dependent on the desired mechanical properties of the material. Tissue engineering of long bone defects for example, will require a rigid scaffold with a compressive strength similar to that of cortical bone (100-150 MPa), which is much higher compared to a scaffold for skin regeneration. [ 44 ] [ 45 ]
There are a few versatile synthetic materials used for many different scaffold applications. One of these commonly used materials is polylactic acid (PLA), a synthetic polymer. PLA – polylactic acid. This is a polyester which degrades within the human body to form lactic acid , a naturally occurring chemical which is easily removed from the body. Similar materials are polyglycolic acid (PGA) and polycaprolactone (PCL): their degradation mechanism is similar to that of PLA, but PCL degrades slower and PGA degrades faster. [ citation needed ] PLA is commonly combined with PGA to create poly-lactic-co-glycolic acid (PLGA). This is especially useful because the degradation of PLGA can be tailored by altering the weight percentages of PLA and PGA: More PLA – slower degradation, more PGA – faster degradation. This tunability, along with its biocompatibility, makes it an extremely useful material for scaffold creation. [ 46 ]
Scaffolds may also be constructed from natural materials: in particular different derivatives of the extracellular matrix have been studied to evaluate their ability to support cell growth. Protein based materials – such as collagen, or fibrin , and polysaccharidic materials- like chitosan [ 47 ] or glycosaminoglycans (GAGs), have all proved suitable in terms of cell compatibility. Among GAGs, hyaluronic acid , possibly in combination with cross linking agents (e.g. glutaraldehyde , water-soluble carbodiimide , etc.), is one of the possible choices as scaffold material.
Due to the covalent attachment of thiol groups to these polymers, they can crosslink via disulfide bond formation. [ 48 ] The use of thiolated polymers ( thiomers ) as scaffold material for tissue engineering was initially introduced at the 4th Central European Symposium on Pharmaceutical Technology in Vienna 2001. [ 49 ] As thiomers are biocompatible, exhibit cellular mimicking properties and efficiently support proliferation and differentiation of various cell types, they are extensively used as scaffolds for tissue engineering. [ 50 ] [ 51 ] [ 52 ] Furthermore thiomers such as thiolated hyaluronic acid [ 53 ] and thiolated chitosan [ 54 ] were shown to exhibit wound healing properties and are subject of numerous clinical trials . [ 55 ] Additionally, a fragment of an extracellular matrix protein, such as the RGD peptide , can be coupled to a non-bioactive material to promote cell attachment. [ 56 ] Another form of scaffold is decellularized tissue. This is a process where chemicals are used to extracts cells from tissues, leaving just the extracellular matrix. This has the benefit of a fully formed matrix specific to the desired tissue type. However, the decellurised scaffold may present immune problems with future introduced cells. [ citation needed ]
A number of different methods have been described in the literature for preparing porous structures to be employed as tissue engineering scaffolds. Each of these techniques presents its own advantages, but none are free of drawbacks.
Molecular self-assembly is one of the few methods for creating biomaterials with properties similar in scale and chemistry to that of the natural in vivo extracellular matrix (ECM), a crucial step toward tissue engineering of complex tissues. [ 57 ] Moreover, these hydrogel scaffolds have shown superiority in in vivo toxicology and biocompatibility compared to traditional macro-scaffolds and animal-derived materials.
These techniques include all the approaches that have been successfully employed for the preparation of non-woven meshes of different polymers . In particular, non-woven polyglycolide structures have been tested for tissue engineering applications: such fibrous structures have been found useful to grow different types of cells. The principal drawbacks are related to the difficulties in obtaining high porosity and regular pore size.
Solvent casting and particulate leaching (SCPL) allows for the preparation of structures with regular porosity, but with limited thickness. First, the polymer is dissolved into a suitable organic solvent (e.g. polylactic acid could be dissolved into dichloromethane ), then the solution is cast into a mold filled with porogen particles. Such porogen can be an inorganic salt like sodium chloride , crystals of saccharose , gelatin spheres or paraffin spheres. The size of the porogen particles will affect the size of the scaffold pores, while the polymer to porogen ratio is directly correlated to the amount of porosity of the final structure. After the polymer solution has been cast the solvent is allowed to fully evaporate, then the composite structure in the mold is immersed in a bath of a liquid suitable for dissolving the porogen: water in the case of sodium chloride, saccharose and gelatin or an aliphatic solvent like hexane for use with paraffin. Once the porogen has been fully dissolved, a porous structure is obtained. Other than the small thickness range that can be obtained, another drawback of SCPL lies in its use of organic solvents which must be fully removed to avoid any possible damage to the cells seeded on the scaffold.
To overcome the need to use organic solvents and solid porogens, a technique using gas as a porogen has been developed. First, disc-shaped structures made of the desired polymer are prepared by means of compression molding using a heated mold. The discs are then placed in a chamber where they are exposed to high pressure CO 2 for several days. The pressure inside the chamber is gradually restored to atmospheric levels. During this procedure the pores are formed by the carbon dioxide molecules that abandon the polymer, resulting in a sponge-like structure. The main problems resulting from such a technique are caused by the excessive heat used during compression molding (which prohibits the incorporation of any temperature labile material into the polymer matrix) and by the fact that the pores do not form an interconnected structure.
This technique does not require the use of a solid porogen like SCPL. First, a synthetic polymer is dissolved into a suitable solvent (e.g. polylactic acid in dichloromethane) then water is added to the polymeric solution and the two liquids are mixed in order to obtain an emulsion . Before the two phases can separate, the emulsion is cast into a mold and quickly frozen by means of immersion into liquid nitrogen . The frozen emulsion is subsequently freeze-dried to remove the dispersed water and the solvent, thus leaving a solidified, porous polymeric structure. While emulsification and freeze-drying allow for a faster preparation when compared to SCPL (since it does not require a time-consuming leaching step), it still requires the use of solvents. Moreover, pore size is relatively small and porosity is often irregular. Freeze-drying by itself is also a commonly employed technique for the fabrication of scaffolds. In particular, it is used to prepare collagen sponges: collagen is dissolved into acidic solutions of acetic acid or hydrochloric acid that are cast into a mold, frozen with liquid nitrogen and then lyophilized .
Similar to the previous technique, the TIPS phase separation procedure requires the use of a solvent with a low melting point that is easy to sublime. For example, dioxane could be used to dissolve polylactic acid, then phase separation is induced through the addition of a small quantity of water: a polymer-rich and a polymer-poor phase are formed. Following cooling below the solvent melting point and some days of vacuum-drying to sublime the solvent, a porous scaffold is obtained. Liquid-liquid phase separation presents the same drawbacks of emulsification/freeze-drying. [ 58 ]
Electrospinning is a highly versatile technique that can be used to produce continuous fibers ranging in diameter from a few microns to a few nanometers. In a typical electrospinning set-up, the desired scaffold material is dissolved within a solvent and placed within a syringe. This solution is fed through a needle and a high voltage is applied to the tip and to a conductive collection surface. The buildup of electrostatic forces within the solution causes it to eject a thin fibrous stream towards the oppositely charged or grounded collection surface. During this process the solvent evaporates, leaving solid fibers leaving a highly porous network. This technique is highly tunable, with variation to solvent, voltage, working distance (distance from the needle to collection surface), flow rate of solution, solute concentration, and collection surface. This allows for precise control of fiber morphology.
On a commercial level however, due to scalability reasons, there are 40 or sometimes 96 needles involved operating at once. The bottle-necks in such set-ups are: 1) Maintaining the aforementioned variables uniformly for all of the needles and 2) formation of "beads" in single fibers that we as engineers, want to be of a uniform diameter. By modifying variables such as the distance to collector, magnitude of applied voltage, or solution flow rate – researchers can dramatically change the overall scaffold architecture.
Historically, research on electrospun fibrous scaffolds dates back to at least the late 1980s when Simon showed that electrospinning could be used to produce nano- and submicron-scale fibrous scaffolds from polymer solutions specifically intended for use as in vitro cell and tissue substrates. This early use of electrospun lattices for cell culture and tissue engineering showed that various cell types would adhere to and proliferate upon polycarbonate fibers. It was noted that as opposed to the flattened morphology typically seen in 2D culture, cells grown on the electrospun fibers exhibited a more rounded 3-dimensional morphology generally observed of tissues in vivo . [ 59 ]
Because most of the above techniques are limited when it comes to the control of porosity and pore size, computer assisted design and manufacturing techniques have been introduced to tissue engineering. First, a three-dimensional structure is designed using CAD software. The porosity can be tailored using algorithms within the software. [ 60 ] The scaffold is then realized by using ink-jet printing of polymer powders or through Fused Deposition Modeling of a polymer melt. [ 61 ]
A 2011 study by El-Ayoubi et al. investigated "3D-plotting technique to produce ( biocompatible and biodegradable ) poly-L-Lactide macroporous scaffolds with two different pore sizes" via solid free-form fabrication (SSF) with computer-aided-design (CAD), to explore therapeutic articular cartilage replacement as an "alternative to conventional tissue repair". [ 62 ] The study found the smaller the pore size paired with mechanical stress in a bioreactor (to induce in vivo-like conditions), the higher the cell viability in potential therapeutic functionality via decreasing recovery time and increasing transplant effectiveness. [ 62 ]
In a 2012 study, [ 63 ] Koch et al. focused on whether Laser-assisted BioPrinting (LaBP) can be used to build multicellular 3D patterns in natural matrix, and whether the generated constructs are functioning and forming tissue. LaBP arranges small volumes of living cell suspensions in set high-resolution patterns. [ 63 ] The investigation was successful, the researchers foresee that "generated tissue constructs might be used for in vivo testing by implanting them into animal models " (14). As of this study, only human skin tissue has been synthesized, though researchers project that "by integrating further cell types (e.g. melanocytes , Schwann cells , hair follicle cells) into the printed cell construct, the behavior of these cells in a 3D in vitro microenvironment similar to their natural one can be analyzed", which is useful for drug discovery and toxicology studies. [ 63 ]
Gustafsson et al. [ 64 ] demonstrated free‐standing, bioactive membranes of cm-sized area, but only 250 nm thin, that were formed by self‐assembly of spider silk at the interface of an aqueous solution. The membranes uniquely combine nanoscale thickness, biodegradability, ultrahigh strain and strength, permeability to proteins and promote rapid cell adherence and proliferation. They demonstrated growing a coherent layer of keratinocytes. These spider silk nanomembranes have also been used to create a static in-vitro model of a blood vessel. [ 65 ]
In situ tissue regeneration is defined as the implantation of biomaterials (alone or in combination with cells and/or biomolecules) into the tissue defect, using the surrounding microenvironment of the organism as a natural bioreactor. [ 66 ] This approach has found application in bone regeneration, [ 67 ] allowing the formation of cell-seeded constructs directly in the operating room. [ 68 ]
A persistent problem within tissue engineering is mass transport limitations. Engineered tissues generally lack an initial blood supply, thus making it difficult for any implanted cells to obtain sufficient oxygen and nutrients to survive, or function properly. [ citation needed ]
Self-assembly methods have been shown to be promising methods for tissue engineering. Self-assembly methods have the advantage of allowing tissues to develop their own extracellular matrix, resulting in tissue that better recapitulates biochemical and biomechanical properties of native tissue. Self-assembling engineered articular cartilage was introduced by Jerry Hu and Kyriacos A. Athanasiou in 2006 [ 69 ] and applications of the process have resulted in engineered cartilage approaching the strength of native tissue. [ 70 ] Self-assembly is a prime technology to get cells grown in a lab to assemble into three-dimensional shapes. To break down tissues into cells, researchers first have to dissolve the extracellular matrix that normally binds them together. Once cells are isolated, they must form the complex structures that make up our natural tissues. [ citation needed ]
The air-liquid surface established by Faraday waves is explored as a template to assemble biological entities for bottom-up tissue engineering. This liquid-based template can be dynamically reconfigured in a few seconds, and the assembly on the template can be achieved in a scalable and parallel manner. Assembly of microscale hydrogels, cells, neuron-seeded micro-carrier beads, cell spheroids into various symmetrical and periodic structures was demonstrated with good cell viability. Formation of 3-D neural network was achieved after 14-day tissue culture. [ 71 ]
It might be possible to print organs, or possibly entire organisms using additive manufacturing techniques. A recent innovative method of construction uses an ink-jet mechanism to print precise layers of cells in a matrix of thermo-reversible gel. Endothelial cells, the cells that line blood vessels, have been printed in a set of stacked rings. When incubated, these fused into a tube. [ 61 ] [ 72 ] This technique has been referred to as "bioprinting" within the field as it involves the printing of biological components in a structure resembling the organ of focus. [ citation needed ]
The field of three-dimensional and highly accurate models of biological systems is pioneered by multiple projects and technologies including a rapid method for creating tissues and even whole organs involve a 3-D printer that can bio-print the scaffolding and cells layer by layer into a working tissue sample or organ. The device is presented in a TED talk by Dr. Anthony Atala, M.D. the Director of the Wake Forest Institute for Regenerative Medicine , and the W.H. Boyce Professor and Chair of the Department of Urology at Wake Forest University, in which a kidney is printed on stage during the seminar and then presented to the crowd. [ 73 ] [ 74 ] [ 75 ] It is anticipated that this technology will enable the production of livers in the future for transplantation and theoretically for toxicology and other biological studies as well. [ citation needed ]
In 2015 Multi-Photon Processing (MPP) was employed for in vivo experiments by engineering artificial cartilage constructs. An ex vivo histological examination showed that certain pore geometry and the pre-growing of chondrocytes (Cho) prior to implantation significantly improves the performance of the created 3-D scaffolds. The achieved biocompatibility was comparable to the commercially available collagen membranes. The successful outcome of this study supports the idea that hexagonal-pore-shaped hybrid organic-inorganic micro-structured scaffolds in combination with Cho seeding may be successfully implemented for cartilage tissue engineering. [ 76 ]
Recently, tissue engineering has advanced with a focus on vascularization. Using Two-Photon Polymerization-based additive manufacturing, synthetic 3D microvessel networks are created from tubular hydrogel structures. These networks can perfuse tissues several cubic millimeters in size, enabling long-term viability and cell growth in vitro. This innovation marks a significant step forward in tissue engineering, facilitating the development of complex human tissue models. [ 77 ]
In 2013, using a 3-D scaffolding of Matrigel in various configurations, substantial pancreatic organoids was produced in vitro. Clusters of small numbers of cells proliferated into 40,000 cells within one week. The clusters transform into cells that make either digestive enzymes or hormones like insulin , self-organizing into branched pancreatic organoids that resemble the pancreas. [ 78 ]
The cells are sensitive to the environment, such as gel stiffness and contact with other cells. Individual cells do not thrive; a minimum of four proximate cells was required for subsequent organoid development. Modifications to the medium composition produced either hollow spheres mainly composed of pancreatic progenitors, or complex organoids that spontaneously undergo pancreatic morphogenesis and differentiation. Maintenance and expansion of pancreatic progenitors require active Notch and FGF signaling, recapitulating in vivo niche signaling interactions. [ 78 ]
The organoids were seen as potentially offering mini-organs for drug testing and for spare insulin-producing cells. [ 78 ]
Aside from Matrigel 3-D scaffolds, other collagen gel systems have been developed. Collagen/hyaluronic acid scaffolds have been used for modeling the mammary gland In Vitro while co-coculturing epithelial and adipocyte cells. The HyStem kit is another 3-D platform containing ECM components and hyaluronic acid that has been used for cancer research. Additionally, hydrogel constituents can be chemically modified to assist in crosslinking and enhance their mechanical properties. [ citation needed ]
In many cases, creation of functional tissues and biological structures in vitro requires extensive culturing to promote survival, growth and inducement of functionality. In general, the basic requirements of cells must be maintained in culture, which include oxygen , pH , humidity , temperature , nutrients and osmotic pressure maintenance. [ citation needed ]
Tissue engineered cultures also present additional problems in maintaining culture conditions. In standard cell culture, diffusion is often the sole means of nutrient and metabolite transport. However, as a culture becomes larger and more complex, such as the case with engineered organs and whole tissues, other mechanisms must be employed to maintain the culture, such as the creation of capillary networks within the tissue. [ citation needed ]
Another issue with tissue culture is introducing the proper factors or stimuli required to induce functionality. In many cases, simple maintenance culture is not sufficient. Growth factors , hormones , specific metabolites or nutrients, chemical and physical stimuli are sometimes required. For example, certain cells respond to changes in oxygen tension as part of their normal development, such as chondrocytes , which must adapt to low oxygen conditions or hypoxia during skeletal development. Others, such as endothelial cells, respond to shear stress from fluid flow, which is encountered in blood vessels . Mechanical stimuli, such as pressure pulses seem to be beneficial to all kind of cardiovascular tissue such as heart valves, blood vessels or pericardium. [ citation needed ]
In tissue engineering, a bioreactor is a device that attempts to simulate a physiological environment in order to promote cell or tissue growth in vitro. A physiological environment can consist of many different parameters such as temperature, pressure, oxygen or carbon dioxide concentration, or osmolality of fluid environment, and it can extend to all kinds of biological, chemical or mechanical stimuli. Therefore, there are systems that may include the application of forces such as electromagnetic forces, mechanical pressures, or fluid pressures to the tissue. These systems can be two- or three-dimensional setups. Bioreactors can be used in both academic and industry applications. General-use and application-specific bioreactors are also commercially available, which may provide static chemical stimulation or a combination of chemical and mechanical stimulation. [ citation needed ]
Cell proliferation and differentiation are largely influenced by mechanical [ 79 ] and biochemical [ 80 ] cues in the surrounding extracellular matrix environment. Bioreactors are typically developed to replicate the specific physiological environment of the tissue being grown (e.g., flex and fluid shearing for heart tissue growth). [ 81 ] This can allow specialized cell lines to thrive in cultures replicating their native environments, but it also makes bioreactors attractive tools for culturing stem cells . A successful stem-cell-based bioreactor is effective at expanding stem cells with uniform properties and/or promoting controlled, reproducible differentiation into selected mature cell types. [ 82 ]
There are a variety of bioreactors designed for 3D cell cultures. There are small plastic cylindrical chambers, as well as glass chambers, with regulated internal humidity and moisture specifically engineered for the purpose of growing cells in three dimensions. [ 83 ] The bioreactor uses bioactive synthetic materials such as polyethylene terephthalate membranes to surround the spheroid cells in an environment that maintains high levels of nutrients. [ 84 ] [ 85 ] They are easy to open and close, so that cell spheroids can be removed for testing, yet the chamber is able to maintain 100% humidity throughout. [ 86 ] This humidity is important to achieve maximum cell growth and function. The bioreactor chamber is part of a larger device that rotates to ensure equal cell growth in each direction across three dimensions. [ 86 ]
QuinXell Technologies now under Quintech Life Sciences from Singapore has developed a bioreactor known as the TisXell Biaxial Bioreactor which is specially designed for the purpose of tissue engineering. It is the first bioreactor in the world to have a spherical glass chamber with biaxial rotation; specifically to mimic the rotation of the fetus in the womb; which provides a conducive environment for the growth of tissues. [ 87 ]
Multiple forms of mechanical stimulation have also been combined into a single bioreactor. Using gene expression analysis, one academic study found that applying a combination of cyclic strain and ultrasound stimulation to pre-osteoblast cells in a bioreactor accelerated matrix maturation and differentiation. [ 88 ] The technology of this combined stimulation bioreactor could be used to grow bone cells more quickly and effectively in future clinical stem cell therapies. [ 89 ]
MC2 Biotek has also developed a bioreactor known as ProtoTissue [ 83 ] that uses gas exchange to maintain high oxygen levels within the cell chamber; improving upon previous bioreactors, since the higher oxygen levels help the cell grow and undergo normal cell respiration . [ 90 ]
Active areas of research on bioreactors includes increasing production scale and refining the physiological environment, both of which could improve the efficiency and efficacy of bioreactors in research or clinical use. Bioreactors are currently used to study, among other things, cell and tissue level therapies, cell and tissue response to specific physiological environment changes, and development of disease and injury. [ citation needed ]
In 2013, a group from the University of Tokyo developed cell laden fibers up to a meter in length and on the order of 100 μm in size. [ 91 ] These fibers were created using a microfluidic device that forms a double coaxial laminar flow. Each 'layer' of the microfluidic device (cells seeded in ECM , a hydrogel sheath, and finally a calcium chloride solution). The seeded cells culture within the hydrogel sheath for several days, and then the sheath is removed with viable cell fibers. Various cell types were inserted into the ECM core, including myocytes , endothelial cells , nerve cell fibers, and epithelial cell fibers. This group then showed that these fibers can be woven together to fabricate tissues or organs in a mechanism similar to textile weaving . Fibrous morphologies are advantageous in that they provide an alternative to traditional scaffold design, and many organs (such as muscle) are composed of fibrous cells.
An artificial organ is an engineered device that can be extra corporeal or implanted to support impaired or failing organ systems. [ 92 ] Bioartificial organs are typically created with the intent to restore critical biological functions like in the replacement of diseased hearts and lungs, or provide drastic quality of life improvements like in the use of engineered skin on burn victims. [ 92 ] While some examples of bioartificial organs are still in the research stage of development due to the limitations involved with creating functional organs, others are currently being used in clinical settings experimentally and commercially. [ 93 ]
Extracorporeal membrane oxygenation (ECMO) machines, otherwise known as heart and lung machines, are an adaptation of cardiopulmonary bypass techniques that provide heart and lung support. [ 94 ] It is used primarily to support the lungs for a prolonged but still temporary timeframe (1–30 days) and allow for recovery from reversible diseases. [ 94 ] Robert Bartlett is known as the father of ECMO and performed the first treatment of a newborn using an ECMO machine in 1975. [ 95 ]
Skin
Tissue-engineered skin is a type of bioartificial organ that is often used to treat burns, diabetic foot ulcers, or other large wounds that cannot heal well on their own. Artificial skin can be made from autografts, allografts, and xenografts. Autografted skin comes from a patient's own skin, which allows the dermis to have a faster healing rate, and the donor site can be re-harvested a few times. Allograft skin often comes from cadaver skin and is mostly used to treat burn victims. Lastly, xenografted skin comes from animals and provides a temporary healing structure for the skin. They assist in dermal regeneration, but cannot become part of the host skin. [ 23 ] Tissue-engineered skin is now available in commercial products. Integra, originally used to only treat burns, consists of a collagen matrix and chondroitin sulfate that can be used as a skin replacement. The chondroitin sulfate functions as a component of proteoglycans, which helps to form the extracellular matrix. [ 96 ] Integra can be repopulated and revascularized while maintaining its dermal collagen architecture, making it a bioartificial organ [ 97 ] Dermagraft, another commercial-made tissue-engineered skin product, is made out of living fibroblasts. These fibroblasts proliferate and produce growth factors, collagen, and ECM proteins, that help build granulation tissue. [ 98 ]
Since the number of patients awaiting a heart transplant is continuously increasing over time, and the number of patients on the waiting list surpasses the organ availability, [ 99 ] artificial organs used as replacement therapy for terminal heart failure would help alleviate this difficulty. Artificial hearts are usually used to bridge the heart transplantation or can be applied as replacement therapy for terminal heart malfunction. [ 100 ] The total artificial heart (TAH), first introduced by Dr. Vladimir P. Demikhov in 1937, [ 101 ] emerged as an ideal alternative. Since then it has been developed and improved as a mechanical pump that provides long-term circulatory support and replaces diseased or damaged heart ventricles that cannot properly pump the blood, restoring thus the pulmonary and systemic flow. [ 102 ] Some of the current TAHs include AbioCor, an FDA-approved device that comprises two artificial ventricles and their valves, and does not require subcutaneous connections, and is indicated for patients with biventricular heart failure. In 2010 SynCardia released the portable freedom driver that allows patients to have a portable device without being confined to the hospital. [ 103 ]
While kidney transplants are possible, renal failure is more often treated using an artificial kidney. [ 104 ] The first artificial kidneys and the majority of those currently in use are extracorporeal, such as with hemodialysis, which filters blood directly, or peritoneal dialysis, which filters via a fluid in the abdomen. [ 104 ] [ 105 ] In order to contribute to the biological functions of a kidney such as producing metabolic factors or hormones, some artificial kidneys incorporate renal cells. [ 104 ] [ 105 ] There has been progress in the way of making these devices smaller and more transportable, or even implantable . One challenge still to be faced in these smaller devices is countering the limited volume and therefore limited filtering capabilities. [ 104 ]
Bioscaffolds have also been introduced to provide a framework upon which normal kidney tissue can be regenerated. These scaffolds encompass natural scaffolds (e.g., decellularized kidneys, [ 106 ] collagen hydrogel, [ 107 ] [ 108 ] or silk fibroin [ 109 ] ), synthetic scaffolds (e.g., poly[lactic-co-glycolic acid] [ 110 ] [ 111 ] or other polymers), or a combination of two or more natural and synthetic scaffolds. These scaffolds can be implanted into the body either without cell treatment or after a period of stem cell seeding and incubation. In vitro and In vivo studies are being conducted to compare and optimize the type of scaffold and to assess whether cell seeding prior to implantation adds to the viability, regeneration and effective function of the kidneys. A recent systematic review and meta-analysis compared the results of published animal studies and identified that improved outcomes are reported with the use of hybrid (mixed) scaffolds and cell seeding; [ 112 ] however, the meta-analysis of these results were not in agreement with the evaluation of descriptive results from the review. Therefore, further studies involving larger animals and novel scaffolds, and more transparent reproduction of previous studies are advisable.
Biomimetics is a field that aims to produce materials and systems that replicate those present in nature. [ 113 ] In the context of tissue engineering, this is a common approach used by engineers to create materials for these applications that are comparable to native tissues in terms of their structure, properties, and biocompatibility. Material properties are largely dependent on physical, structural, and chemical characteristics of that material. Subsequently, a biomimetic approach to system design will become significant in material integration, and a sufficient understanding of biological processes and interactions will be necessary. Replication of biological systems and processes may also be used in the synthesis of bio-inspired materials to achieve conditions that produce the desired biological material. Therefore, if a material is synthesized having the same characteristics of biological tissues both structurally and chemically, then ideally the synthesized material will have similar properties. This technique has an extensive history originating from the idea of using natural phenomenon as design inspiration for solutions to human problems. Many modern advancements in technology have been inspired by nature and natural systems, including aircraft, automobiles, architecture, and even industrial systems. Advancements in nanotechnology initiated the application of this technique to micro- and nano-scale problems, including tissue engineering. This technique has been used to develop synthetic bone tissues, vascular technologies, scaffolding materials and integration techniques, and functionalized nanoparticles. [ 113 ]
In 2018, scientists at Brandeis University reported their research on soft material embedded with chemical networks which can mimic the smooth and coordinated behavior of neural tissue. This research was funded by the U.S. Army Research Laboratory . [ 114 ] The researchers presented an experimental system of neural networks, theoretically modeled as reaction-diffusion systems . Within the networks was an array of patterned reactors, each performing the Belousov-Zhabotinsky (BZ) reaction. These reactors could function on a nanoliter scale. [ 115 ]
The researchers state that the inspiration for their project was the movement of the blue ribbon eel . The eel's movements are controlled by electrical impulses determined by a class of neural networks called the central pattern generator . Central Pattern Generators function within the autonomic nervous system to control bodily functions such as respiration, movement, and peristalsis . [ 116 ]
Qualities of the reactor that were designed were the network topology, boundary conditions , initial conditions, reactor volume, coupling strength, and the synaptic polarity of the reactor (whether its behavior is inhibitory or excitatory). [ 116 ] A BZ emulsion system with a solid elastomer polydimethylsiloxane (PDMS) was designed. Both light and bromine permeable PDMS have been reported as viable methods to create a pacemaker for neural networks. [ 115 ]
The history of the tissue engineering market can be divided into three major parts. The time before the crash of the biotech market in the early 2000s, the crash and the time afterward.
Most early progress in tissue engineering research was done in the US. This is due to less strict regulations regarding stem cell research and more available funding than in other countries. This leads to the creation of academic startups many of them coming from Harvard or MIT . Examples are BioHybrid Technologies whose founder, Bill Chick, went to Harvard Medical School and focused on the creation of artificial pancreas. Another example would be Organogenesis Inc. whose founder went to MIT and worked on skin engineering products. Other companies with links to the MIT are TEI Biosciences, Therics and Guilford Pharmaceuticals. [ 8 ] The renewed interest in biotechnologies in the 1980s leads to many private investors investing in these new technologies even though the business models of these early startups were often not very clear and did not present a path to long term profitability. [ 117 ] Government sponsors were more restrained in their funding as tissue engineering was considered a high-risk investment. [ 8 ]
In the UK the market got off to a slower start even though the regulations on stem cell research were not strict as well. This is mainly due to more investors being less willing to invest in these new technologies which were considered to be high-risk investments. [ 117 ] Another problem faced by British companies was getting the NHS to pay for their products. This especially because the NHS runs a cost-effectiveness analysis on all supported products. Novel technologies often do not do well in this respect. [ 117 ]
In Japan, the regulatory situation was quite different. First cell cultivation was only allowed in a hospital setting and second academic scientists employed by state-owned universities were not allowed outside employment until 1998. Moreover, the Japanese authorities took longer to approve new drugs and treatments than there US and European counterparts. [ 117 ]
For these reasons in the early days of the Japanese market, the focus was mainly on getting products that were already approved elsewhere in Japan and selling them. Contrary to the US market the early actors in Japan were mainly big firms or sub-companies of such big firms, such as J-TEC, Menicon and Terumo, and not small startups. [ 117 ] After regulatory changes in 2014, which allowed cell cultivation outside of a hospital setting, the speed of research in Japan increased and Japanese companies also started to develop their own products. [ 117 ]
Soon after the big boom, the first problems started to appear. There were problems getting products approved by the FDA and if they got approved there were often difficulties in getting insurance providers to pay for the products and getting it accepted by health care providers. [ 117 ] [ 118 ]
For example, organogenesis ran into problems marketing its product and integrating its product in the health system. This partially due to the difficulties of handling living cells and the increased difficulties faced by physicians in using these products over conventional methods. [ 117 ]
Another example would be Advanced Tissue Sciences Dermagraft skin product which could not create a high enough demand without reimbursements from insurance providers. Reasons for this were $4000 price-tag and the circumstance that Additionally Advanced Tissue Sciences struggled to get their product known by physicians. [ 117 ]
The above examples demonstrate how companies struggled to make profit. This, in turn, lead investors to lose patience and stopping further funding. In consequence, several Tissue Engineering companies such as Organogenesis and Advanced Tissue Sciences filed for bankruptcy in the early 2000s. At this time, these were the only ones having commercial skin products on the market. [ 118 ]
The technologies of the bankrupt or struggling companies were often bought by other companies which continued the development under more conservative business models. [ 118 ] Examples of companies who sold their products after folding were Curis [ 118 ] and Intercytex. [ 117 ]
Many of the companies abandoned their long-term goals of developing fully functional organs in favor of products and technologies that could turn a profit in the short run. [ 117 ] Examples of these kinds of products are products in the cosmetic and testing industry.
In other cases such as in the case of Advanced Tissue Sciences, the founders started new companies. [ 117 ]
In the 2010s the regulatory framework also started to facilitate faster time to market especially in the US as new centres and pathways were created by the FDA specifically aimed at products coming from living cells such as the Center for Biologics Evaluation and Research . [ 117 ]
The first tissue engineering products started to get commercially profitable in the 2010s. [ 118 ]
In Europe, regulation is currently split into three areas of regulation: medical devices , medicinal products , and biologics . Tissue engineering products are often of hybrid nature, as they are often composed of cells and a supporting structure. While some products can be approved as medicinal products, others need to gain approval as medical devices. [ 119 ] Derksen explains in her thesis that tissue engineering researchers are sometimes confronted with regulation that does not fit the characteristics of tissue engineering. [ 120 ]
New regulatory regimes have been observed in Europe that tackle these issues. [ 121 ] An explanation for the difficulties in finding regulatory consensus in this matter is given by a survey conducted in the UK. [ 119 ] The authors attribute these problems to the close relatedness and overlap with other technologies such as xenotransplantation . It can therefore not be handled separately by regulatory bodies. [ 119 ] Regulation is further complicated by the ethical controversies associated with this and related fields of research (e.g. stem cells controversy , ethics of organ transplantation ). The same survey as mentioned above [ 119 ] shows on the example of autologous cartilage transplantation that a specific technology can be regarded as 'pure' or 'polluted' by the same social actor.
Two regulatory movements are most relevant to tissue engineering in the European Union . These are Directive 2004/23/EC on standards of quality and safety for the sourcing and processing of human tissues [ 122 ] which was adopted by the European Parliament in 2004 and a proposed Human Tissue-Engineered Products regulation. The latter was developed under the auspices of the European Commission DG Enterprise and presented in Brussels in 2004. [ 123 ] | https://en.wikipedia.org/wiki/Tissue_engineering |
Tissue engineered heart valves (TEHV) offer a new and advancing proposed treatment of creating a living heart valve for people who are in need of either a full or partial heart valve replacement . Currently, there are over a quarter of a million prosthetic heart valves implanted annually, [ 1 ] and the number of patients requiring replacement surgeries is only suspected to rise and even triple over the next fifty years. [ 2 ] While current treatments offered such as mechanical valves or biological valves are not deleterious to one's health, they both have their own limitations in that mechanical valves necessitate the lifelong use of anticoagulants while biological valves are susceptible to structural degradation and reoperation. [ 2 ] [ 3 ] Thus, in situ (in its original position or place) tissue engineering of heart valves serves as a novel approach that explores the use creating a living heart valve composed of the host's own cells that is capable of growing, adapting, and interacting within the human body's biological system. [ 4 ]
Research has not yet reached the stage of clinical trials.
Various biomaterials , whether they are biological, synthetic, or a combination of both, can be used to create scaffolds, which when implanted in a human body can promote host tissue regeneration . [ 5 ] First, cells from the patient in which the scaffold will be implanted in are harvested. These cells are expanded and seeded into the created scaffold, which is then inserted inside the human body. [ 6 ] The human body serves as a bioreactor, which allows the formation of an extracellular matrix (ECM) along with fibrous proteins around the scaffold to provide the necessary environment for the heart and circulatory system . [ 7 ] The initial implantation of the foreign scaffold triggers various signaling pathways guided by the foreign body response for cell recruitment from neighboring tissues. [ 2 ] The new nanofiber network surrounding the scaffold mimics the native ECM of the host body. [ 8 ] Once cells begin to populate the cell, the scaffold is designed to gradually degrade, leaving behind a constructed heart valve made of the host body's own cells that is fully capable of cell repopulation and withstanding environmental changes within the body. [ 9 ] The scaffold designed for tissue engineering is one of the most crucial components because it guides tissue construction, viability, and functionality long after implantation and degradation. [ citation needed ]
Biological scaffolds can be created from human donor tissue or from animals; however, animal tissue is often more popular since it is more widely accessible and more plentiful. [ 10 ] Xenograft , from a donor of a different species from the recipient, heart valves can be from either pigs, cows, or sheep. [ 8 ] If either human or animal tissue is used, the first step in creating useful scaffolds is decellularization , which means to remove the cellular contents all the while preserving the ECM matrix, [ 11 ] which is advantageous compared to manufacturing synthetic scaffolds from scratch. Many decellularization methods have been used such as the use of nonionic and ionic detergents that disrupt cellular material interactions or the use of enzymes to cleave peptide bonds, RNA, and DNA. [ 8 ]
There are also current approaches that are manufacturing scaffolds and coupling them with biological cues. [ 2 ] Fabricated scaffolds can also be manufactured using either biological, synthetic, or a combination of both materials from scratch to mimic the native heart valve observed using imaging techniques. Since the scaffold is created from raw materials, there is much more flexibility in controlling the scaffold's properties and can be more tailored. Some types of fabricated scaffolds include solid 3-D porous scaffolds that have a large pore network that permits the flow through of cellular debris, allowing further tissue and vascular growth. [ 12 ] 3-D porous scaffolds can be manufactured through 3-D printing or various polymers, ranging from polyglycolic acid (PGA) and polylactic acid (PLA) to more natural polymers such as collagen. [ 8 ]
Fibrous scaffolds have the potential to closely match the structure of ECM through its use of fibers, which have a high growth factor . Techniques to produce fibrous scaffolds include electrospinning , [ 13 ] [ 11 ] in which a liquid solution of polymers is stretched from an applied high electric voltage to produce thin fibers. Conversely to the 3-D porous scaffolds, fibrous scaffolds have a very small pore size that prevents the pervasion of cells within the scaffold. [ 14 ]
Hydrogel scaffolds are created by cross-linking hydrophilic polymers through various reaction such as free radical polymerization or conjugate addition reaction . [ 8 ] Hydrogels are beneficial because they have a high water content, which allows the ease of nutrients and small materials to pass through. [ 15 ]
The biocompatibility of surgically implanted foreign biomaterial refers to the interactions between the biomaterial and the host body tissue. Cell line as well as cell type such as fibroblasts can largely impact tissue responses towards implanted foreign devices by changing cell morphology. [ 16 ] Thus the cell source as well as protein adsorption , which is dependent on biomaterial surface property, play a crucial role in tissue response and cell infiltration at the scaffold site. [ citation needed ]
Implantation of any foreign device or material through the means of surgery results in at least some degree of tissue trauma. Therefore, especially when removing a native heart valve either partially or completely, the tissue trauma will trigger a cascade of inflammatory responses and elicit acute inflammation . During the initial phase of acute inflammation, vasodilation occurs to increase blood flow to the wound site along with the release of growth factors, cytokines, and other immune cells. Furthermore, cells release reactive oxygen species and cytokines, which cause secondary damage to surrounding tissue. [ 17 ] These chemical factors then proceed to promote the recruitment of other immune responsive cells such as monocytes or white blood cells, which help foster the formation of a blood clot and protein-rich matrix. [ citation needed ]
If the acute inflammatory response persists, the body then proceeds to undergo chronic inflammation . During this continual and systemic inflammation phase, one of the primary driving forces is the infiltration of macrophages . The macrophages and lymphocytes induce the formation of new tissues and blood vessels to help supply nutrients to the biomaterial site. New fibrous tissue then encapsulates the foreign biomaterial in order to minimize interactions between the biomaterial and surrounding tissue. While the prolonging of chronic inflammation may be a likely indicator for an infection, inflammation may on occasion be present upwards to five years post-surgery. Chronic inflammation marked by the presence of fibrosis and inflammatory cells was observed in rat cells 30 days post implantation of a device. [ 18 ]
Following chronic inflammation, mineralization occurs approximately 60 days after implantation due to the buildup of cellular debris and calcification , which has the potential to compromise the functionality of biocompatible implanted devices in vivo.
Under normal physiological conditions, inflammatory cells protect the body from foreign objects, and the body undergoes a foreign body reaction based on the adsorption of blood and proteins on the biomaterial surface. In the first two to four weeks post implant, there is an association between biomaterial adherent macrophages and cytokine expression near the foreign implant site, which can be explored using semi-quantitative RT-PCR . [ 19 ] Macrophages fuse together to form foreign body giant cells (FBGCs), which similarly express cytokine receptors on their cell membranes and actively participate in the inflammatory response. Device failure in organic polyether polyurethane (PEU) pacemakers compared to silicone rubber showcases that the foreign body response may indeed lead to degradation of biomaterials, causing subsequent device failures. The utilization of to prevent functionality and durability compromise is proposed to minimize and slow the rate of biomaterial degradation. [ 19 ]
Tissue engineered heart valves offer certain advantages over traditional biological and mechanical valves:
Many risks and challenges must still be addressed and explored before tissue engineered heart valves can fully be clinically implemented:
Studies performed seeded scaffolds made of polymers with various cell lines in vitro , in which the scaffolds degraded over time while leaving behind a cellular matrix and proteins. The first study on tissue engineering of heart valves was published in 1995. [ 11 ] During 1995 and 1996, Shinoka used a scaffold made of polyglycolic acid (PGA), approved by the FDA for human implantation, and seeded it with sheep endothelial cells and fibroblasts with the goal of replacing a sheep's pulmonary valve leaflet. [ 22 ] What resulted from Shinoka's study was an engineered heart valve that was much thicker and more rigid, which prompted Hoerstrup to conduct a study to replace all three pulmonary valve leaflets in a sheep using a poly-4-hydroxybutyrate (P4HB) coated PGA scaffold and sheep endothelial cells and myofibroblast. [ 23 ]
Another option studied was using decellularized biological scaffolds and seeding them with their corresponding cells in vitro . [ 21 ] In 2000, Steinhoff implanted a decellularized sheep pulmonary valve scaffold seeded with sheep endothelial cells and myofibroblasts. [ 24 ] Dohmen then created a decellularized cryopreserved pulmonary allograft scaffold and seeded it with human vascular endothelial cells to reconstruct the right ventricular outflow tract (RVOT) in a human patient in 2002. [ 25 ] Perry in 2003 seeded a P4HB coated PGA scaffold with sheep mesenchymal stem cells in vitro ; however, an in vivo study was not performed. [ 26 ] In 2004, Iwai conducted a study using a poly(lactic-co-glycolic acid) PLGA compounded with collagen microsponge sphere scaffold, which was seeded with endothelial and smooth muscle cells at the site of a dog's pulmonary artery. [ 27 ] Sutherland in 2005 utilized a sheep mesenchymal stem cell seeded PGA and poly-L-lactic acid (PLLA) scaffold to replace all three pulmonary valve leaflets in a sheep. [ 28 ]
A handful of studies utilized tissue engineering of heart valves in vivo in animal models and humans. In 2000, Matheny conducted a study in which he used a pig's small intestinal submucosa to replace one pulmonary valve leaflet. [ 29 ] Limited studies have also been conducted in a clinical setting. For instance in 2001, Elkins implanted SynerGraft treated decellularized human pulmonary valves in patients. [ 30 ] Simon similarly used SynerGraft decellularized pig valves for implantation in children; [ 31 ] however, these valves widely failed as there were no host cells but rather high amounts of inflammatory cells found at the scaffold site instead. [ 32 ] [ 33 ] [ 8 ] Studies led by Dohmen, Konertz, and colleagues in Berlin, Germany involved the implantation of a biological pig valve in 50 patients who underwent the Ross operation from 2002 to 2004. [ 33 ] Using a decellularized porcine xenograft valve, also called Matrix P, in adults with a median age of 46 years, the aim of the study was to offer a proposal for pulmonary valve replacement. While some patients died postoperatively and had to undergo reoperation, the short-term results appear to be going well as the valve is behaving similarly to a native, healthy valve. [ 34 ] One animal trial combined the transcatheter aortic valve replacement (TAVR) procedure with tissue engineered heart valves (TEHVs). A TAVR stent integrated with human cell-derived extracellular matrix was implanted and examined in sheep, in which the valve upheld structural integrity and cell infiltration, allowing the potential clinical application to extend TAVR to younger patients. [ 35 ]
While many in vitro and in vivo studies have been tested in animal models, the translation from animal models to humans has not begun. Factors such as the size of surgical cut sites, duration of the procedure, and available resources and cost must all be considered. [ 36 ] Synthetic nanomaterials have the potential to advance scaffoldings used in tissue engineering of heart valves. The use of nanotechnology could help expand beneficial properties of fabricated scaffolds such as higher tensile strength. [ 37 ] | https://en.wikipedia.org/wiki/Tissue_engineering_of_heart_valves |
Tissue growth is the process by which a tissue increases its size . In animals, tissue growth occurs during embryonic development , post-natal growth, and tissue regeneration . The fundamental cellular basis for tissue growth is the process of cell proliferation , which involves both cell growth and cell division occurring in parallel. [ 1 ] [ 2 ] [ 3 ] [ 4 ]
How cell proliferation is controlled during tissue growth to determine final tissue size is an open question in biology. Uncontrolled tissue growth is a cause of cancer .
Differential rates of cell proliferation within an organ can influence proportions, as can the orientation of cell divisions , and thus tissue growth contributes to shaping tissues along with other mechanisms of tissue morphogenesis .
For some animal tissues, such as mammalian skin , it is clear that the growth of the skin is ultimately determined by the size of the body whose surface area the skin covers. This suggests that cell proliferation in skin stem cells within the basal layer is likely to be mechanically controlled to ensure that the skin covers the surface of the entire body. Growth of the body causes mechanical stretching of the skin, which is sensed by skin stem cells within the basal layer and consequently leads to both an increased rate of cell proliferation as well as promoting the planar orientation of stem cell divisions to produce new skin stem cells , rather than only producing differentiating supra-basal daughter cells.
Cell proliferation in skin stem cells within the basal layer can be driven by the mechanically-regulated YAP / TAZ family of transcriptional co-activators , which bind to TEAD -family DNA binding transcription factors in the nucleus to activate target gene expression and thereby drive cell proliferation .
For other animal tissues, such as the bones of the skeleton or the internal mammalian organs intestine , pancreas , kidney or brain , it remains unclear how developmental gene regulatory networks encoded in the genome lead to organs of such different sizes and proportions.
Although different animal tissues grow at different rates and produce organs of very different proportions, the overall growth rate of the entire animal body can be modulated by circulating hormones of the Insulin / IGF-1 family, which activate the PI3K/AKT/mTOR pathway in many cells of the body to increase the average rate of both cell growth and cell division , leading to increased cell proliferation rates in many tissues. In mammals, production of IGF-1 is induced by another circulating hormone called Growth Hormone . Excessive production of Growth Hormone or IGF-1 is responsible for giantism while insufficient production of these hormones is responsible for dwarfism .
Adult animal tissues such as skin or intestine maintain their size but undergo constant turnover of cells by proliferation of stem cells and progenitor cells while undergoing an equivalent loss of differentiated daughter cells via sloughing off. Gradients of Wnt signaling pathway activity appear to have a fundamental role in maintaining proliferation of stem and progenitor cells, at least in the intestine, and possibly also in skin.
Upon tissue damage, there is an upregulation in the activity of many pathways that control tissue growth, including the YAP / TAZ pathway, Wnt signaling pathway , and growth factors that activate the PI3K/AKT/mTOR pathway . | https://en.wikipedia.org/wiki/Tissue_growth |
Tissue microarrays (also TMA s) consist of paraffin blocks in which up to 1000 [ 1 ] separate tissue cores are assembled in array fashion to allow multiplex histological analysis .
The major limitations in molecular clinical analysis of tissues include the cumbersome nature of procedures, limited availability of diagnostic reagents and limited patient sample size. The technique of tissue microarray was developed to address these issues.
Multi-tissue blocks were first introduced by H. Battifora in 1986 with his so-called “multitumor (sausage) tissue block" and modified in 1990 with its improvement, "the checkerboard tissue block" . In 1998, J. Kononen and collaborators developed the current technique, which uses a novel sampling approach to produce tissues of regular size and shape that can be more densely and precisely arrayed.
In the tissue microarray technique, a hollow needle is used to remove tissue cores as small as 0.6 mm in diameter from regions of interest in paraffin-embedded tissues such as clinical biopsies or tumor samples. These tissue cores are then inserted in a recipient paraffin block in a precisely spaced, array pattern. Sections from this block are cut using a microtome , mounted on a microscope slide and then analyzed by any method of standard histological analysis. Each microarray block can be cut into 100 – 500 sections, which can be subjected to independent tests. Tests commonly employed in tissue microarray include immunohistochemistry , and fluorescent in situ hybridization . Tissue microarrays are particularly useful in analysis of cancer samples.
One variation is a Frozen tissue array .
The use of tissue microarrays in combination with immunohistochemistry has been a preferred method to study and validate cancer biomarkers in various defined cancer patient cohorts . The possibility to assemble a large number of representative cancer samples from a defined patient cohort that also has a corresponding clinical database, provides a powerful resource to study how different protein expression patterns correlate with different clinical parameters. Since patient samples are assembled into the same block, sections can be stained with the same protocol to avoid experimental variability and technical artefacts. Clinical cancer patient cohorts and corresponding tissue microarray sets have been used to study diagnostic, prognostic and treatment predictive cancer biomarkers in most forms of cancer, including lung, breast, colorectal and renal cell cancer. [ 2 ] [ 3 ] [ 4 ] [ 5 ]
Immunohistochemistry combined with tissue microarrays has also been used with success in large scale efforts to create a map of protein expression on a more global scale. [ 6 ] | https://en.wikipedia.org/wiki/Tissue_microarray |
Tissue nanotransfection ( TNT ) is an electroporation -based technique capable of gene and drug cargo delivery or transfection at the nanoscale. Furthermore, TNT is a scaffold-less tissue engineering (TE) technique that can be considered cell-only or tissue inducing depending on cellular or tissue level applications. The transfection method makes use of nanochannels to deliver cargo to tissues topically.
Cargo delivery methods rely on carriers, for example nanoparticles , viral vectors , or physical approaches such as gene guns , microinjection , or electroporation. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ] [ 9 ] The various methods can be limited by size constraints or their ability to efficiently deliver cargo without damaging tissue. Electroporation is a physical method which harnesses an electric field to open pores in the normally semi-permeable cell membrane through which cargo can enter. In this process, the charges can be used to drive cargo in a specific direction.
Bulk electroporation (BEP) is the most conventional electroporation method. Benefits come in the form of high throughput and minimal set-up times. [ 7 ] The downside of BEP is that the cell membrane experiences an uneven distribution of the electric field and many membranes receive irreversible damage from which they can no longer close, thus leading to low cell viability.
Attempts have been made to miniaturize electroporation such as microelectroporation (MEP) [ 10 ] and nanochannel electroporation (NEP) [ 11 ] which uses electroporation approached to deliver cargo through micro /nanochannels respectively. These techniques have shown to have higher efficiency of delivery, increased uniform transfection, and increased cell viability compared to BEP. [ 12 ]
Tissue nanotransfection uses custom fabricated nanochannel arrays for nanoscale delivery of genetic cargo directly onto the surface of the skin. The postage stamp-sized chip is placed directly on the skin and an electric current is induced lasting for milliseconds to deliver the gene cargo with precise control. This approach delivers ample amounts of reprogramming factors to single-cells, creating potential for a powerful gene transfection and reprogramming method. [ 11 ] [ 12 ] The delivered cargo then transforms the affected cells into a desired cell type without first transforming them to stem cells. TNT is a novel technique and has been used on mice models to successfully transfect fibroblasts into neuron-like cells along with rescue of ischemia in mice models with induced vasculature and perfusion . [ 13 ] Current methods require the fabricated TNT chip to be placed on the skin and the loading reservoir filled with a gene solution. An electrode ( cathode ) is placed into the well with a counter electrode ( anode ) placed under the chip intradermally (into the skin). The electric field generated delivers the genes. [ 13 ]
Initial TNT experiments showed that genes could be delivered to the skin of mice. [ 13 ] Once this was confirmed, a cocktail of gene factors ( ABM ) used by Vierbuchen [ 14 ] and collaborators to reprogram fibroblast into neurons was used. [ 12 ] [ 13 ] Delivery of these factors demonstrated successful reprogramming in-vivo and signals propagated from the epidermis to the dermis skin layers. This phenomenon is believed to be mediated by extracellular vesicles [ 15 ] and potentially other factors [18]. Successful reprogramming was determined by performing histology and electrophysiological tests to confirm the tissue behaved as functional neurons. [ 13 ]
Beyond inducing neurons, Gallego-Perez et al. also set out to induce endothelial cells in an ischemic mouse limb that, without proper blood flow, becomes necrotic and decays. Using a patented cocktail of plasmids ( Etv2, Fli1, Foxc2, or EFF) , these factors were delivered to the tissue above the surgery site. Using various methods, including histology and laser speckle imaging , perfusion and the establishment of new vasculature was verified as early as 7 days post-treatment. [ 13 ]
The technique was developed to combat the limitations of current approaches, such as a shortage in donors to supply cell sources and the need to induce pluripotency . [ 14 ] [ 15 ] [ 16 ] [ 17 ] [ 18 ] [ 19 ] Reprogramming cells in vivo takes advantage of readily available cells, bypassing the need for pre-processing. [ 20 ] [ 21 ] Most reprogramming methods have a heavy reliance on viral transfection. [ 22 ] [ 23 ] TNT allows for implementation of a non-viral approach which is able to overcome issues of capsid size, increase safety, and increase deterministic reprogramming. [ 13 ]
The tissue nanotransfection technique was developed as a method to efficiently and benignly deliver cargo to living tissues. This technique builds on the high-throughput nanoelectroporation methods developed for cell reprogramming applications by Lee and Gallego-Perez of Ohio State's Chemical and Biomolecular Engineering department. Sen (Surgery/Regenerative Medicine) adapted this technology, in collaboration with Lee in Engineering, for in vivo tissue reprogramming applications with Gallego-Perez serving the role of a shared fellow between the two programs. Development was a joint effort between OSU's College of Engineering and College of Medicine led by Gallego-Perez (Ph.D), Lee (Ph.D), and Sen (Ph.D).
This technology was fabricated using cleanroom techniques and photolithography and deep reactive ion etching (DRIE) of silicon wafers to create nanochannels with backside etching of a reservoir for loading desired factors as described in Gallego-Perez et al 2017. [ 13 ] This chip is then connected to an electrical source capable of delivering an electrical field to drive the factors from the reservoir into the nanochannels, and onto the contacted tissue. Later, with support from Xuan, Sen developed the current version of the tissue nanotransfection chip. [ 24 ] | https://en.wikipedia.org/wiki/Tissue_nanotransfection |
Tissue remodeling is the reorganization or renovation of existing tissues . Tissue remodeling can be either physiological or pathological. The process can either change the characteristics of a tissue such as in blood vessel remodeling, or result in the dynamic equilibrium of a tissue such as in bone remodeling . Macrophages repair wounds and remodel tissue by producing extracellular matrix and proteases to modify that specific matrix. [ 1 ]
A myocardial infarction induces tissue remodeling of the heart in a three-phase process: inflammation , proliferation , and maturation. Inflammation is characterized by massive necrosis in the infarcted area. Inflammatory cells clear the dead cells. In the proliferation phase, inflammatory cells die by apoptosis , being replaced by myofibroblasts which produce large amounts of collagen . In the maturation phase, myofibroblast numbers are reduced by apoptosis, allowing for infiltration by endothelial cells (for blood vessels) and cardiomyocytes (heart tissue cells). Usually, however, much of the tissue remodeling is pathological, resulting in a large amount of fibrous tissue. [ 2 ] By contrast, aerobic exercise can produce beneficial cardiac tissue remodeling in those suffering from left ventricular hypertrophy . [ 3 ]
Programmed cellular senescence contributes to beneficial tissue remodeling during embryonic development of the fetus . [ 4 ]
In a brain stroke the penumbra area surrounding the ischemic event initially undergoes a damaging remodeling, but later transitions to a tissue remodeling characterized by repair. [ 5 ]
Vascular remodeling refers to a compensatory change in blood vessel walls due to plaque growth. Vascular expansion is called positive remodeling, whereas vascular constriction is called negative remodeling. [ 6 ]
Tissue remodeling occurs in adipose tissue with increased body fat. [ 7 ] In obese subjects, this remodeling is often pathological, characterized by excessive inflammation and fibrosis. [ 8 ]
This article about biomedical engineering is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Tissue_remodeling |
Tissue residue is the concentration of a chemical or compound in an organism's tissue or in a portion of an organism's tissue. [ 1 ] Tissue residue is used in aquatic toxicology to help determine the fate of chemicals in aquatic systems, bioaccumulation of a substance, or bioavailability of a substance, account for multiple routes of exposure (ingestion, absorption, inhalation), and address an organism's exposure to chemical mixtures. [ 2 ] A tissue residue approach to toxicity testing is considered a more direct and less variable measure of chemical exposure and is less dependent on external environmental factors than measuring the concentration of a chemical in the exposure media. [ 3 ]
In general, tissue residue approaches are used for chemicals that bioaccumulate or for bioaccumulative chemicals. [ 2 ] The majority of these substances are organic compounds that are not easily metabolized by organisms and have long environmental persistence. Examples of these chemicals include polychlorinated dibenzodioxins , furans , biphenyls , DDT and its metabolites , and dieldrin . [ 2 ]
The use of tissue residues in assessing toxicity and bioaccumulation may also be referred to as the tissue residue-effects approach (TRA), critical body residue (CBR), or tissue residue-based toxicity tests. [ 1 ] [ 4 ]
Historically, aquatic toxicology toxicity tests have focused on water-based approaches where concentration of a toxicant is determined by its concentration in the water. [ 2 ] Although tissue residue use and concepts have existed for over 100 years due to interest in narcosis and anesthesia, it was not widely used in toxicology. [ 5 ] The first known study of tissue residue in environmental toxicology was reported in 1912 by White and Thomas who investigated the effects of copper exposure to fish using whole-body copper concentrations. [ 5 ]
Since the 1980s, there has been rapid growth in the tissue residue approach to toxicology. [ 5 ] The water-based approach has been re-evaluated due to challenges in assessing the toxicity of bioaccumulating chemicals. [ 2 ] Water-based approaches are not always an accurate estimation of the concentration of a bioaccumulating chemical in an organism, nor does the water-based approach incorporate the multiple routes of exposure of an organism to a toxicant and the additive effects across these routes. [ 2 ]
The use of tissue residue allows an investigator to: account for multiple routes of exposure, account for toxicokinetic differences between species, account for factors that alter bioavailability and potentially address exposure of an organism to a chemical mixture. [ 1 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] Tissue residue also has the ability to represent temporal and spatial exposure or an organism, [ 4 ] [ 8 ] as well as clarify the cause-effect relationship of chemicals. These relationships are often distorted by uncertainty in chemical bioavailability. [ 4 ] The mechanism of action for a chemical depends on the internal tissue concentration, thus tissue residue gives researchers a more direct estimate of the residue-effect (dose-response) relationship. [ 3 ] [ 9 ] Tissue residue is also less variable than other measures of chemical exposure. [ 2 ] [ 8 ]
In addition to the aforementioned advantages of tissue residue use, the U.S. EPA also states that this approach explicitly considers exposure through diet, will support identification and investigation of a chemical's mode of action, incorporate the effects of an organism's metabolism on accumulation and allow for experimental verification between lab and field studies. [ 6 ]
The majority of issues with tissue residue arise in the interpretation of tissue residue data. [ 1 ] [ 3 ] Interpretation complication can be caused by choice of endpoints, species choice, life stage sensitivity, data quality, and toxicity data extrapolation. [ 3 ] Choice of tissue for tissue residue analysis can also be difficult and has an effect on tissue residue data. When choosing tissue, a scientist needs to consider: mode and mechanism of action of chemical being tested, site of toxic action for the chemical and species combination being studied and strength of the tissue residue-response relationship. There is also a lack of reliable tissue residue relationships available for comparison. [ 3 ] [ 5 ]
Although use of tissue residue can account for multiple routes of exposure, it cannot identify the routes of exposure. Tissue residue also cannot account for biotransformation of organic chemicals. [ 3 ] [ 5 ] If a chemical is biotransformed, the concentration of the parent chemical is lower, but the metabolites may still be toxic. [ 3 ] Tissue residue approaches are not as useful for chemicals with short half-lives because an organism will only be sporadically exposed. [ 1 ] Overall, tissue residue is meant to complement data from water-based approaches, not replace them. [ 4 ]
The U.S. Environmental Protection Agency (USEPA) has incorporated tissue residue through the development of the Biotic Ligand Model as well as water quality standards for copper. USEPA has also recently published draft aquatic life criteria for selenium using a tissue-based approach. USEPA is currently working on incorporating tissue residue into standards for bioaccumulating chemicals, which are usually hydrophobic with a log octanol-water partition coefficient greater than 5 (log Kow>5). [ 2 ] Canada uses tissue residue formally in guidelines called tissue residue guidelines (TRGs), which are primarily used for protecting wildlife that consume aquatic life. [ 10 ] [ 11 ]
There is a lack of formal use of tissue residue in Europe.
Australia and New Zealand both use tissue residue-based approaches for biomonitoring programs for mussels and oysters.
There are two comprehensive aquatic toxicology databases Aquatic Toxicology Databases available for tissue residue in the United States. The first is the Toxicity Residue Database maintained by the USEPA. [ 3 ] The second is the Environmental residue-effects database (ERED) maintained by the U.S. Army Corps of Engineers. [ 3 ] Currently, the majority of the data available is derived from acute lethal response studies. [ 3 ]
Tissue residue of metals in invertebrate prey organisms may reduce uncertainty in estimating exposure from multiple routes. [ 8 ] This may be especially important in early life stages of an organism or for species listed under the Endangered Species Act (ESA). [ 8 ] However, it is challenging to develop a suitable approach to assessing metal toxicity through tissue residue because water quality can have a large influence on metal toxicity. With the exception of organometallic compounds , no generalized approaches have been created for analyzing metals in tissue residue, although site-specific and species-specific approaches have been successfully developed and used, especially for invertebrates. [ 12 ] A recent paper examined tissue-residue toxicity for copper and cadmium in fish and found low variability among species for both metals compared to aqueous-exposure toxicity metrics. [ 13 ] These results indicate that whole-body concentrations of metals in fish may be useful for Environmental Quality Guidelines, forensic evaluation, and ecological risk assessment. An additional benefit includes the potential to characterize a contaminated ecosystem based on elevated whole-body metal concentrations resulting from acclimation.
Fish are able to quickly metabolize and eliminate PAHs , therefore tissue residue of parent PAH compounds will not provide adequate information on exposure to the organism. [ 8 ] PAH exposure in fish has been associated with reproductive impairment, immune deficiency, and liver lesions as well as other health problems. [ 8 ] In contrast, invertebrates do not metabolize and excrete PAHs as efficiently as fish, therefore an investigator can better understand location and temporal patterns of bioavailable PAHs through tissue residue of these invertebrates. [ 8 ]
Unlike PAHs, tissue residue of PCBs for fish can provide reliable information on exposure and toxicity. [ 8 ] The tissue residue of PCBs in fish can provide vital information in an exposure assessment because fish generally receive PCBs through exposure via the food web. There are currently two screening approaches for PCBs in fish based on PCB body burdens. [ 8 ]
Both the United States and United Kingdom have mussel watch monitoring programs. Although these programs differ in many ways, both use tissue residues to establish biological effects, such as survival and body condition, of chemicals present. In contrast to the passive nature of the mussel watch monitoring programs, tissue residue has also been applied in in-situ bioassays in the United States, United Kingdom and Canada.
Tissue residue guidelines were developed for tributyltin (TBT) for the Harbor Island Superfund site, Lower Duwamish Superfund site and the Portland Harbor Superfund site. At the Harbor Island Superfund site, tissue trigger levels were developed to provide guidance on remediation action. [ 14 ] Tissue residue toxicity reference value (TRV) was developed for TBT regarding mortality and growth at the Lower Duwamish Superfund site. Tissue residue TRVs were also developed for TBT, as well as many other chemicals, for use in the Portland Harbor Superfund site work. [ 14 ]
Ecological risk assessment aims to source of contamination to exposure to a toxicity endpoint. [ 5 ] [ 8 ] [ 14 ] This requires a risk assessor to identify and estimate exposure pathways. [ 8 ] Tissue residue is the only approach that inherently accounts for toxicity due to multiple exposure pathways. [ 1 ] [ 5 ] [ 6 ] [ 7 ] There is also a need in risk assessment to understand the bioaccumulation of chemicals4, as well as a direct estimation of bioavailability . [ 8 ] Modeling food web exposure is difficult in risk assessment and requires many assumptions but this uncertainty can be reduced through tissue residue. [ 8 ] Tissue residue may also allow provide a link between ecological risk assessment and human health risk assessment. [ 5 ] [ 14 ]
The issues with using tissue residue in risk assessment are similar to the disadvantages listed above. [ 14 ] | https://en.wikipedia.org/wiki/Tissue_residue |
Tissue selectivity is a topic in distribution (pharmacology) and property of some drugs . It refers to when a drug occurs in disproportionate concentrations and/or has disproportionate effects in specific tissues relative to other tissues. [ 1 ] An example of such drugs are selective estrogen receptor modulators (SERM) like tamoxifen , which show estrogenic effects in some tissues and antiestrogenic effects in other tissues. Another example is peripherally-selective drugs , which do not cross the blood-brain-barrier into the central nervous system and hence are tissue-selective for the periphery.
This pharmacology -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Tissue_selectivity |
Tissue stress (tissue adaptive syndrome) is an unspecific adaptive reaction universal for all tissues of adult organism which forms in tissue as a response to various external influences. The latter are tissue cells’ damage, overload of their specialized functions or regulatory influences.
According to tissue adaptive syndrome (TAS) concept, this adaptive mechanism (see adaptation) comes into effect in damaged tissue (see Tissue (biology) ) as a result of concurrence of two events. The first one is accumulation of TAS effectors in tissue ( comutons , chalones , and contactins ), which possess a unique feature of tissue specificity in their action on homologous tissue cells without species specificity. The second one is increase in sensitivity of damaged cells to these regulators, as it was demonstrated on the example of comuton. These effectors cause tissue-specific self-damage of homologous cells via disturbance of their ion homeostasis and energy-production processes. As a result, unspecific reaction to damage (CURD) is activated in the cells. This universal physiological reaction plays a role of TAS executive mechanism. Thus, the adaptive function of tissue stress is brought into action using such CURD properties as increase of cell unspecific resistance, as well as influence on the rate of cell metabolic processes. It is obvious that in the case of TAS these changes have to be tissue-specific, since they are initiated by way of cell self-damage under tissuespecific influence of TAS effectors.
As is well known the CURD consists of two phases. In the process of a slight damage of the cell, the phase of metabolism stimulation is forming in it. When the cell is slightly damaged, it begins to form the phase of metabolism stimulation. Strong damaging influences initiate the CURD phase of metabolism inhibition in the cell.
According to the TAS concept, the protective effect of the tissue stress is realized in the case of forming of CURD metabolism stimulation phase by TAS effectors as a result of acceleration of reparative processes in the damaged cell. In the process of forming of CURD phase of metabolism inhibition by the above effectors the protective influence of tissue stress develops a result of cell reactivity decrease in response to the external damaging influences.
The main feature of the tissue stress is its formation with participation of the tissuespecific effectors of intratissue intercellular interactions – comutons, chalones and contactins, which are produced by the cells of a tissue under a stressor's influence. This distinguishes the tissue stress from the general adaptive syndrome, which is realized via hormones – effectors of interorgan interactions (see Stress (biological) ). Regional (local) stress forms with participation of not one but several tissues making up an organ or a body part. This is why it can be believed that regional stress-reaction is realized with the participation of effectors of intraorgan intertissue interactions. Finally, the cell stress is realized via intracellular mechanisms, without any participation of intercellular interactions. In the latter case the CURD formation and synthesis of heat shock proteins act as “self-defense” mechanism of the cell.
Another distinctive feature of tissue stress is the principle of formation of its executive mechanism, the CURD, via tissuespecific self-damage of homologous tissue cells. Despite the fact that TAS, just as the cell stress, is realized via CURD, the TAS has a variety of features which distinguish it from the cell stress, the key one being the tissue-selectivity of CURD initiation under TAS effectors influence. In addition, under cell stress the cell protection is realized with CURD participation only via “passive” mechanism. It consists in the formation of the protective phase of this physiological reaction. Meanwhile, under tissue stress, its protective function may be carried out both the “passive” and “active” CURD-induced mechanisms. Thus, the cell stress mechanism is just one of the two instruments with which TAS protects the cells of homologous tissue. The third difference between tissue and cell stresses lies in ability of the former not only to increase but also to decrease the unspecific resistance of the cells. Meanwhile, the cell stress concept considers only the first possibility.
At the present moment, two physiological functions of tissue stress, which are realized in the process of participation of its adaptive mechanism, can be considered. One of them is expressed in an increase of cell specialized functions stability in the conditions of prolonged functional load. Another tissue stress function is to regulate homologous tissue cell mass in various physiological conditions.
It is well known that only some part of tissue functional units participate in its cells specialized functions realization (Barcroft, 1937). Because of universality of this phenomenon it was named “the law of intermittent activity of functioning structures” (Kryshanovskii, 1973; Kryshanovskii, 1974). According to this law, functional units of actively functioning tissue (or cells) form two populations where one is in “intensive functioning” state and the other one – is in “resting” state.
Thereat the “rest” is not a passive state since there active reparation of cellular structures occurs damaged in the course of specialized functions performing by cells. “Intermittent” pattern of tissue cells specialized functions realization is that the cells pass from one population to another when the tissue is in intensive functioning mode. In such a way the cells damaged in consequence of intensive functioning gain an offing to recover in “resting” population. Meanwhile, recovered cells pass from the “resting” population into “intensively functioning” one. It is safe to say that such organization of tissue functioning favors stability of its cells functions performance. Yet, the mechanisms which regulate cells passage from one population to another on intratissue level are unknown.
Considering the law of “intermittent activity of functioning structures” one can talk about two results of the TAS mechanism action on the cells of actively functioning tissue. In conditions where the TAS effector (effectors) forms CURD phase of metabolism stimulation one should expect an acceleration of reparative processes in the cells of “resting” population. Obviously that will promote accelerated recovery of such cells and their pass to intensively functioning cell population. In case if TAS mechanism forms the CURD phase of metabolism inhibition in intensively functioning cells population this will lead to cell signaling inhibition and promote cells “autonomy” from other external influences. Such autonomy may provoke an inhibition of cell's specialized functions in mentioned population in case if they are stimulated by external regulatory influences. An inhibition of cells specialized functions by the TAS mechanism may promote defense of intensively functioning cells from self-damage and also their pass into the “resting” state. Thus, the properties of tissue stress executive mechanism – CURD – allow it to raise tissue functions stability in conditions of continuous intensive activity in many ways.
According to the TAS concept, tissue stress possess the ability to regulate the cell mass of homologous tissue via executive mechanism described above – the CURD. As in the case of cells specialized functions regulation there are two ways of tissue-specific control of homologous tissue cell mass. These are cells unspecific resistance modulation and influencing the speed of physiological processes occurring in the cell.
Tissue stress mechanism able to control tissue cell mass influencing both its mitotic and apoptotic (see Apoptosis ) activities tissue-specifically. In case if TAS effectors form CURD phase of metabolism stimulation one should expect acceleration of proliferative (see Proliferation ) pool cells passage through mitotic cycle (MC). Herewith there will be also an acceleration of cells maturation and ageing. This will provoke an increase of both mitotic and apoptotic activity in tissue. On the contrary, formation of CURD phase of metabolism protective inhibition should result in opposite results – an inhibition of all mentioned processes and, as a result, to inhibition of both mitotic and apoptotic activities. One cannot exclude the possibility that tissue stress mechanism considered able to regulate apoptosis through inhibition of its energy-dependent stage. As concerns the modulation of cells unspecific resistance by tissue stress mechanism, this property of CURD allows to regulate cells entrance into MC as well as their entrance into apoptosis.
Regulation of tissue cell mass by the TAS mechanism can be carried out in two physiological regimes – ether by formation of “conservative” or “dynamic” phase of this adaptive reaction. TAS conservative phase is forming under the influence of “weak” unspecific external damaging or “load” influences on cells specialized functions. Here tissue stress provides intratissue adaptation by preservation of the existing cell population in the tissue. It is achieved by raise of cells unspecific resistance under the influence of tissue-specific self-damage of cells by TAS effectors. This prevents entrance of postmitotic cells both into MC and apoptosis. The TAS dynamic phase forms under “strong” external unspecific damaging or “loading” influences on cells specialized functions. According to TAS concept in dynamic phase of tissue stress a summation of damaging influence of stressor (stressors) with cells self-damage by TAS effectors occurs. This leads to stimulation of proliferation (see Proliferation ) and to an increase of apoptotic activity (see Apoptosis ) simultaneously. Thus, in above case adaptive function of tissue stress realizes by replacement of damaged, dying cells by descendants of cells more resistant to stressor(s) influence.
As is clear from the foregoing, according to the TAS concept tissue stress mechanism effect on homologous tissue cells is multifarious. It may protect them against the unspecific damaging influences as well as to increase stability of tissue specialized functions in the conditions of prolonged intensive functional activity. Simultaneously, the same mechanism performs intratissue control of cell mass of homologous tissue. | https://en.wikipedia.org/wiki/Tissue_stress |
Tissue typing is a procedure in which the tissues of a prospective donor and recipient are tested for compatibility prior to transplantation . Mismatched donor and recipient tissues can lead to rejection of the tissues. There are multiple methods of tissue typing.
During tissue typing, an individual's human leukocyte antigens (HLA) are identified. [ 1 ] HLA molecules are presented on the surface of cells and facilitate interactions between immune cells (such as dendritic cells and T cells ) that lead to adaptive immune responses . [ 2 ] If HLA from the donor is recognized by the recipient's immune system as different from the recipient's own HLA, an immune response against the donor tissues can be triggered. [ 3 ] More specifically, HLA mismatches between organ donors and recipients can lead to the development of anti-HLA donor-specific antibodies (DSAs). [ 4 ] DSAs are strongly associated with the rejection of donor tissues in the recipient, and their presence is considered an indicator of antibody-mediated rejection. [ 5 ] When donor and recipient HLA are matched, donor tissues are significantly more likely to be accepted by the recipient's immune system. [ 3 ] During tissue typing, a number of HLA genes should be typed in both the donor and recipient, including HLA Class I A , B , and C genes, as well as HLA Class II DRB1 , DRB3 , DRB4 , DRB5 , DQA1 , DQB1 , DPA1 , and DPB1 genes. [ 6 ] HLA typing is made more difficult by the fact that the HLA region is the most genetically variable region in the human genome. [ 7 ]
One of the first methods of tissue typing was through serological typing. In this technique, a donor's blood cells are HLA typed by mixing them with serum containing anti-HLA antibodies . If the antibodies recognize their epitope on the donor's HLA then complement activation occurs leads to cell lysis and death, allowing the cells to take up a dye ( trypan blue ). This allows for identification of the cells' HLA based indirectly on the specificity of the known antibodies in the serum. This method has been used widely since it is simple, quick, and low-cost; however, the huge variability in HLA alleles means that serum containing antibodies specific to the HLA of the cells being tested may not be available. [ 6 ] [ 3 ] Serological typing does not give a clear picture of the HLA region and does not always result in successful HLA typing, so many laboratories have stopped using it in favor of more effective methods. [ 6 ] [ 8 ]
Recently, other more effective approaches have emerged, including the use of polymerase chain reaction ( PCR ) based on sequence-specific primers (SSP) or sequence-specific oligonucleotide probes (SSOP). [ 3 ] [ 6 ] However, SSP-PCR can be both time and resource consuming. [ 8 ] SSOP-PCR is better for HLA typing large numbers of individuals, for example, large numbers of donors for bone marrow registries. [ 8 ] RT-PCR is another approach to HLA typing that is fast and versatile, but it is expensive. [ 6 ]
Reference strand-mediated conformational analysis (RSCA) is yet another method used for HLA typing. In this method, an unknown HLA sample is mixed with a reference allele and run in a gel by electrophoresis . [ 8 ] RSCA is limited by the number of HLA reference alleles available since the HLA region is so diverse. [ 8 ]
Direct DNA sequencing is currently considered the best method of HLA typing, either by Sanger sequencing or next generation sequencing , though it can also be time-consuming and is one of the more expensive methods. [ 6 ] [ 8 ] RNA sequencing can also be used, but many labs do not as RNA is unstable and prone to degradation. [ 8 ] | https://en.wikipedia.org/wiki/Tissue_typing |
On April 14, 1912, the Titanic collided with an iceberg , damaging the hull's plates below the waterline on the starboard side, causing the front compartments to flood. The ship then sank two hours and forty minutes later, with approximately 1,496 fatalities as a result of drowning or hypothermia . [ 1 ] Since then, many conspiracy theories have been suggested regarding the disaster. These theories have been refuted by subject-matter experts .
The pack ice theory is not a conspiracy theory since it accepts that the sinking was an accident. However, it differs from the commonly accepted theory and is considered implausible by the vast majority of historians.
Captain L. M. Collins, a former member of the Ice Pilotage Service, based a conclusion on three pieces of evidence and going off of his own experience of ice navigation and witness statements given at the two post-disaster enquiries, that what the Titanic hit was not an iceberg but low-lying pack ice . His book, called The Sinking of the Titanic: The Mystery Solved (2003) goes into further detail about the events.
One of the controversial [ 5 ] [ 6 ] and elaborate theories surrounding the sinking of the Titanic was advanced by Robin Gardiner in his book Titanic: The Ship That Never Sank? (1998). [ 7 ] Gardiner draws on several events and coincidences that occurred in the months, days, and hours leading up to the sinking of the Titanic , and concludes that the ship that sank was in fact Titanic ' s sister ship Olympic , disguised as Titanic , as an insurance scam by its owners, the International Mercantile Marine Group, controlled by American financier J. P. Morgan that had acquired the White Star Line in 1902.
Researchers Bruce Beveridge and Steve Hall took issue with many of Gardiner's claims in their book Olympic and Titanic: The Truth Behind the Conspiracy (2004). [ 5 ] Author Mark Chirnside has also raised serious questions about the switch theory. [ 6 ] British historian Gareth Russell, for his part, calls the theory "so painfully ridiculous that one can only lament the thousands of trees which lost their lives to provide the paper on which it has been articulated." He notes that, "since the sister ships had significant interior architectural and design differences, switching them secretly in a week would be nearly impossible from a practical standpoint. A switch would also not be economically worthwhile, since the ship's owners could have simply damaged the ship while docked (for instance, by setting a fire) and collected the insurance money from that 'accident', which would have been far less severe, and infinitely less stupid, than sailing her out into the middle of the Atlantic with thousands of people, and their luggage, on board, and ramming her into an iceberg". [ citation needed ]
Another claim that started gaining traction in late 2017, alleges that J. P. Morgan deliberately sank the ship in order to kill off several millionaires who were in opposition to the Federal Reserve . Some of the wealthiest men in the world were aboard the Titanic for her maiden voyage, several of whom, including John Jacob Astor IV , Benjamin Guggenheim , and Isidor Straus , were allegedly opposed to the creation of a U.S. central bank . [ 8 ] No evidence of their opposition to Morgan's centralized banking ideas has been found: Astor and Guggenheim never spoke publicly on the subject, while Straus spoke in favour of the concept. [ 9 ] [ 10 ] All three men died during the sinking. Conspiracy theorists suggest that Morgan arranged to have the men board the ship and then sunk it to eliminate them. [ 11 ] Morgan cancelled his ticket for Titanic 's maiden voyage due to a reported illness, while Guggenheim had not purchased a ticket before Morgan's cancellation. [ 12 ] Morgan, nicknamed the " Napoleon of Wall Street", had helped create General Electric , U.S. Steel , and International Harvester , is the namesake of JPMorgan Chase , and was credited with almost single-handedly saving the U.S. banking system during the Panic of 1907 . Morgan did have a hand in the creation of the Federal Reserve, and owned the International Mercantile Marine , which owned the White Star Line, and thus the Titanic . [ 13 ]
Morgan, who had attended the Titanic 's launching in 1911, had booked a personal suite aboard the ship with his own private promenade deck and a bath equipped with specially designed cigar holders. He was reportedly booked on the ship's maiden voyage but instead cancelled the trip and remained at the French resort of Aix-les-Bains to enjoy his morning massages and sulfur baths. [ 13 ] His allegedly last-minute cancellation has fuelled speculation among conspiracy theorists that he knew of the ship's fate. [ 11 ] [ 14 ] This theory has been refuted by Titanic experts George Behe, Don Lynch , and Ray Lepien who have each provided alternate, more widely-accepted theories as to why Morgan cancelled his trip. [ 15 ]
Conspiracy theorist Stew Peters has advanced an alternative version of the theory, alleging the Rothschilds were behind both the Federal Reserve and the Titanic ’s sinking. Peters also claimed that the Titan submersible implosion was orchestrated via sabotage in order to prevent its own passengers from discovering that the Titanic was sunk by a "controlled demolition" instead of an iceberg. [ 16 ]
Another theory involves Titanic ' s watertight doors. This theory suggests that if these doors had been opened, the Titanic would have settled on an even keel and therefore, perhaps, remained afloat long enough for rescue ships to arrive. However, this theory has been rebutted for two reasons: first, the first four compartments were naturally watertight, thus it was impossible to lower the concentration of water in the bow significantly. Second, Bedford and Hacket have shown by calculations that any significant amount of water aft of boiler room No. 4 would have resulted in capsizing of the Titanic , which would have occurred about 30 minutes earlier than the actual time of sinking. [ 17 ] Additionally, the lighting would have been lost about 70 minutes after the collision due to the flooding of the boiler rooms. [ 17 ] Bedford and Hacket also analyzed the hypothetical case that there were no bulkheads at all. Then, the vessel would have capsized about 70 minutes before the actual time of sinking and lighting would have been lost about 40 minutes after the collision.
Later, in a 1998 documentary titled Titanic: Secrets Revealed , [ 18 ] the Discovery Channel ran model simulations which also rebutted this theory. The simulations indicated that opening Titanic ' s watertight doors would have caused the ship to capsize earlier than it actually sank by more than a half-hour, supporting the findings of Bedford and Hacket.
Titanic researchers continued to debate the causes and mechanics of the ship ' s breakup. According to his book, A Night to Remember , Walter Lord described Titanic as assuming an "absolutely perpendicular" position shortly before its final plunge. [ 19 ] This view remained largely unchallenged even after the wreck was discovered by Robert Ballard in 1985, which confirmed that Titanic had broken in two pieces at or near the surface; paintings by noted marine artist Ken Marschall and as imagined onscreen in James Cameron 's film Titanic , both depicted the ship attaining a steep angle prior to the breakup. [ 20 ] Most researchers acknowledged that Titanic ' s aft expansion joint —designed to allow for flexing of the hull in a seaway—played little to no role in the ship's breakup, [ 21 ] though debate continued as to whether the ship had broken from the top downwards or from the bottom upwards.
In 2005, a History Channel expedition to the wreck site scrutinized two large sections of Titanic ' s keel, which constituted the portion of the ship's bottom from immediately below the site of the break. With assistance from naval architect Roger Long, the team analysed the wreckage and developed a new break-up scenario [ 22 ] which was publicised in the television documentary Titanic's Final Moments: Missing Pieces in 2006. One hallmark of this new theory was the claim that Titanic ' s angle at the time of the breakup was far less than had been commonly assumed—according to Long, no greater than 11°.
Long also suspected that Titanic ' s breakup may have begun with the premature failure of the ship's aft expansion joint, and ultimately exacerbated the loss of life by causing Titanic to sink faster than anticipated. In 2006, the History Channel sponsored dives on Titanic ' s newer sister ship, Britannic , which verified that the design of Britannic ' s expansion joints was superior to that incorporated in the Titanic . [ 23 ] To further explore Long's theory, the History Channel commissioned a new computer simulation by JMS Engineering. The simulation, whose results were featured in the 2007 documentary Titanic's Achilles Heel , partially refuted Long's suspicions by demonstrating that Titanic ' s expansion joints were strong enough to deal with any and all stresses the ship could reasonably be expected to encounter in service and, during the sinking, actually outperformed their design specifications. [ 24 ] But, most important is that the expansion joints were part of the superstructure, which was situated above the strength deck (B-deck) and therefore above the top of the structural hull girder. Thus, the expansion joints had no meaning for the support of the hull. They played no role in the breaking of the hull. They simply opened up and parted as the hull flexed or broke beneath them.
Brad Matsen's 2008 book Titanic's Last Secrets endorses the expansion joint theory. [ 25 ]
One common oversight is the fact that the collapse of the first funnel at a relatively shallow angle occurred when the forward expansion joint, over which several funnels stays crossed, opened as the hull was beginning to stress. The opening of the joint stretched and snapped the stays. The forward momentum of the ship as she took a sudden lurch forwards and downwards sent the unsupported funnel toppling onto the starboard bridge wing.
One theory that would support the fracturing of the hull is that the Titanic partly grounded on the shelf of ice below the waterline as she collided with the iceberg, perhaps damaging the keel and underbelly. Later during the sinking, it was noticed that Boiler Room four flooded from below the floor grates rather than from over the top of the watertight bulkhead. This would be consistent with additional damage along the keel compromising the integrity of the hull.
This claim states that fire began in one of Titanic 's coal bunkers approximately 10 days prior to the ship's departure, and continued to burn for several days into the voyage. [ 26 ] [ 27 ] Fires occurred frequently on board steamships due to spontaneous combustion of the coal. [ 28 ] The fires had to be extinguished with fire hoses, by moving the coal on top to another bunker and by removing the burning coal and feeding it into the furnace. [ 29 ] This event has led some authors to theorize that the fire exacerbated the effects of the iceberg collision, by reducing the structural integrity of the hull and a critical bulkhead . [ 30 ] [ 31 ]
Senan Molony has suggested that attempts to extinguish the fire – by shoveling burning coals into the engine furnaces – may have been the primary reason for the Titanic steaming at full speed prior to the collision, despite ice warnings. [ 32 ] Most experts disagree. Samuel Halpern has concluded that "the bunker fire would not have weakened the watertight bulkhead sufficiently to cause it to collapse." [ 33 ] [ 34 ] Also, it has been alternatively suggested that the coal bunker fire actually helped Titanic to last longer during the sinking and prevented the ship from rolling over to starboard after the impact, due to the subtle port list created by the moving of coal inside the ship prior to the encounter with the iceberg. [ 35 ] Some of these foremost Titanic experts have published a detailed rebuttal of Molony's claims. [ 36 ] | https://en.wikipedia.org/wiki/Titanic_conspiracy_theories |
Titanium(II) oxide ( Ti O ) is an inorganic chemical compound of titanium and oxygen. It can be prepared from titanium dioxide and titanium metal at 1500 °C. [ 1 ] It is non-stoichiometric in a range TiO 0.7 to TiO 1.3 and this is caused by vacancies of either Ti or O in the defect rock salt structure. [ 1 ] In pure TiO 15% of both Ti and O sites are vacant, [ 1 ] as the vacancies allow metal-metal bonding between adjacent Ti centres. Careful annealing can cause ordering of the vacancies producing a monoclinic form which has 5 TiO units in the primitive cell that exhibits lower resistivity. [ 2 ] A high temperature form with titanium atoms with trigonal prismatic coordination is also known. [ 3 ] Acid solutions of TiO are stable for a short time then decompose to give hydrogen: [ 1 ]
Gas-phase TiO shows strong bands in the optical spectra of cool ( M-type ) stars. [ 4 ] [ 5 ] In 2017, TiO was claimed to be detected in an exoplanet atmosphere for the first time; a result which is still debated in the literature. [ 6 ] [ 7 ] Additionally, evidence has been obtained for the presence of the diatomic molecule TiO in the interstellar medium. [ 8 ] | https://en.wikipedia.org/wiki/Titanium(II)_oxide |
Titanium(III) chloride is the inorganic compound with the formula TiCl 3 . At least four distinct species have this formula; additionally hydrated derivatives are known. TiCl 3 is one of the most common halides of titanium and is an important catalyst for the manufacture of polyolefins .
In TiCl 3 , each titanium atom has one d electron, rendering its derivatives paramagnetic , that is, the substance is attracted into a magnetic field. Solutions of titanium(III) chloride are violet, which arises from excitations of its d -electron . The colour is not very intense since the transition is forbidden by the Laporte selection rule .
Four solid forms or polymorphs of TiCl 3 are known. All feature titanium in an octahedral coordination sphere. These forms can be distinguished by crystallography as well as by their magnetic properties, which probes exchange interactions . β-TiCl 3 crystallizes as brown needles. Its structure consists of chains of TiCl 6 octahedra that share opposite faces such that the closest Ti–Ti contact is 2.91 Å. This short distance indicates strong metal–metal interactions (see figure in upper right). The three violet "layered" forms, named for their color and their tendency to flake, are called alpha (α), gamma (γ), and delta (δ). In α-TiCl 3 , the chloride anions are hexagonal close-packed . In γ-TiCl 3 , the chlorides anions are cubic close-packed . Finally, disorder in shift successions, causes an intermediate between alpha and gamma structures, called the δ form. The TiCl 6 share edges in each form, with 3.60 Å being the shortest distance between the titanium cations. This large distance between titanium cations precludes direct metal-metal bonding. In contrast, the trihalides of the heavier metals hafnium and zirconium engage in metal-metal bonding. Direct Zr–Zr bonding is indicated in zirconium(III) chloride . The difference between the Zr(III) and Ti(III) materials is attributed in part to the relative radii of these metal centers. [ 2 ]
Two hydrates of titanium(III) chloride are known, i.e. complexes containing aquo ligands . These include the pair of hydration isomers [Ti(H 2 O) 6 ]Cl 3 and [Ti(H 2 O) 4 Cl 2 ]Cl(H 2 O) 2 . The former is violet and the latter, with two molecules of water of crystallization, is green. [ 3 ]
TiCl 3 is produced usually by reduction of titanium(IV) chloride . Older reduction methods used hydrogen : [ 4 ]
More modern techniques prefer aluminum ; the product is sold as a mixture with aluminium trichloride , TiCl 3 ·AlCl 3 . [ 5 ]
TiCl 3 can also be produced by the reaction of titanium metal and hot, concentrated hydrochloric acid ; the reaction does not proceed at room temperature, as titanium is passivated against most mineral acids by a thin surface layer of titanium dioxide .
Treating TiCl 3 with tetrahydrofuran (THF) gives the light-blue colored, [ 6 ] meridional complex, TiCl 3 ( THF ) 3 : [ 7 ]
TiCl 3 ·AlCl 3 gives the same product. [ 5 ]
An analogous dark green complex arises from complexation with dimethylamine . In a reaction where all ligands are exchanged, TiCl 3 is a precursor to the blue-colored complex Ti(acac) 3 . [ 8 ]
The more reduced titanium(II) chloride is prepared by the thermal disproportionation of TiCl 3 at 500 °C. The reaction is driven by the loss of volatile TiCl 4 : [ 9 ]
The trichloride is a Lewis acid , forming ternary hexahalide complexes with stoichiometry M 3 TiCl 6 . These have structures that depend on the cation (M + ) added. [ 10 ] Caesium chloride treated with titanium(II) chloride and hexachlorobenzene produces crystalline CsTi 2 Cl 7 . In these structures Ti 3+ exhibits octahedral coordination geometry. [ 11 ]
TiCl 3 is the main Ziegler–Natta catalyst , responsible for most industrial production of polyethylene . The catalytic activities depend strongly on the polymorph of the TiCl 3 (α vs. β vs. γ vs. δ) and the method of preparation. [ 12 ]
TiCl 3 is also a specialized reagent in organic synthesis, useful for reductive coupling reactions, often in the presence of added reducing agents such as zinc. It reduces oximes to imines . [ 13 ] Titanium trichloride can reduce nitrate to ammonium ion thereby allowing for the sequential analysis of nitrate and ammonia. [ 14 ] Slow deterioration occurs in air-exposed titanium trichloride, often resulting in erratic results, such as in reductive coupling reactions . [ 15 ]
TiCl 3 and most of its complexes are typically handled under air-free conditions to prevent reactions with oxygen and moisture. Samples of TiCl 3 can be relatively air stable or pyrophoric . [ 16 ] [ 17 ] | https://en.wikipedia.org/wiki/Titanium(III)_chloride |
Titanium(III) oxide is the inorganic compound with the formula Ti 2 O 3 . A black semiconducting solid, it is prepared by reducing titanium dioxide with titanium metal at 1600 °C. [ 3 ]
Ti 2 O 3 adopts the Al 2 O 3 (corundum) structure. [ 3 ] It is reactive with oxidising agents. [ 3 ] At around 200 °C, there is a transition from semiconducting to metallic conducting. [ 3 ] Titanium(III) oxide occurs naturally as the extremely rare mineral in the form of tistarite . [ 4 ]
Other titanium(III) oxides include LiTi 2 O 4 and LiTiO 2 . [ 5 ]
This inorganic compound –related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Titanium(III)_oxide |
Titanium SDK is an open-source framework that allows the creation of native mobile applications on platforms iOS and Android from a single JavaScript codebase . [ 2 ] It is presently developed by non-profit software foundation TiDev, Inc. [ 3 ] [ 4 ]
In February 2013, Business Insider estimated that 10% of all smartphones worldwide ran Titanium-built apps. [ 5 ] As of 2017 [update] , Titanium had amassed over 950,000 developer registrations. [ 6 ]
The core component of the Titanium software ecosystem is the Apache-licensed software development kit , Titanium SDK. Alloy, a Titanium-based model–view–controller framework, is a related project presently maintained and developed by TiDev, Inc for use with the Titanium SDK.
Titanium SDK was originally developed and maintained by Appcelerator, Inc, then later by Axway, Inc after Axway purchased Appcelerator in 2016. [ 7 ] Today the Titanium SDK and related projects are developer-maintained under direction of non-profit Alabama corporation TiDev, Inc. based in Centreville, Alabama . [ 8 ]
When it was introduced in December 2008, Titanium was intended for developing cross-platform desktop applications and was sometimes compared to Adobe Air . [ 9 ] [ 10 ] However, it added support for developing iPhone and Android mobile applications in June 2009, and in 2012, Titanium Desktop was spun off into a separate, community-driven project named TideSDK . [ 11 ] [ 12 ] Support for developing iPad-based tablet apps was added in April 2010. [ 13 ] BlackBerry support was announced in June 2010, [ 14 ] and has been in beta since April 2013. Tizen support was also added in April 2013 with the 3.1.0 Titanium Studio and SDK releases. The latest addition to the platform in 2016 has been Hyperloop, a technology to access native API's on iOS, Android and Windows with JavaScript. [ 15 ]
In April 2010, Appcelerator expanded the Titanium product line with the Titanium Tablet SDK. The Titanium Tablet SDK draws heavily from the existing support for iPhone, but it also includes native support for iPad-only user interface controls such as split views and popovers. Initially the mobile SDK only supported development for iPad, but support now includes Android-based tablets as well.
In June 2011, Appcelerator released Studio and Titanium Mobile 1.7. [ 16 ] Studio is a full open standards IDE that is derived from Aptana Studio which Appcelerator acquired in January 2011.
In June 2013, Jeff Haynie, Appcelerator's CEO, announced that the company had begun Ti.Next, a project to rewrite the Titanium SDK in Javascript for improved performance and to bring Titanium's end users, who write in Javascript, closer to the internal code. [ 17 ]
In January 2016, Appcelerator was acquired by Axway , a global software company with more than 11,000 public- and private-sector customers in 100 countries. [ 18 ] Since then, the Indie plans have been made free again, including native API access with Hyperloop. [ 19 ]
The core features of Titanium SDK include:
All application source code gets deployed to the mobile device where it is interpreted [ 20 ] using a JavaScript engine ; Mozilla's Rhino is used on Android, BlackBerry, and Apple's JavascriptCore is used on iOS. [ 21 ] In 2011 it was announced that a port to Google's V8 JavaScript engine is in development which, when complete, will significantly improve performance. [ 22 ] Program loading takes longer than it does for programs developed with the native SDKs, as the interpreter and all required libraries must be loaded before interpreting the source code on the device can begin.
Titanium provides APIs for:
12.4.0.GA
with all minor updates and release candidates. [ 23 ] | https://en.wikipedia.org/wiki/Titanium_SDK |
Titanium aluminide (chemical formula TiAl ), commonly gamma titanium , is an intermetallic chemical compound . It is lightweight and resistant to oxidation [ 1 ] and heat, but has low ductility . The density of γ-TiAl is about 4.0 g/cm 3 . It finds use in several applications including aircraft, jet engines, sporting equipment and automobiles. [ citation needed ] The development of TiAl based alloys began circa 1970. The alloys have been used in these applications only since about 2000.
Titanium aluminide has three major intermetallic compounds: gamma titanium aluminide ( gamma TiAl , γ-TiAl ), alpha 2-Ti 3 Al and TiAl 3 . Among the three, gamma TiAl has received the most interest and applications.
Gamma TiAl has excellent mechanical properties and oxidation and corrosion resistance at elevated temperatures (over 600 °C), which makes it a possible replacement for traditional Ni based superalloy components in aircraft turbine engines.
TiAl-based alloys have potential to increase the thrust-to-weight ratio in aircraft engines. This is especially the case with the engine's low-pressure turbine blades and the high-pressure compressor blades. These are traditionally made of Ni-based superalloy, which is nearly twice as dense as TiAl-based alloys. Some gamma titanium aluminide alloys retain strength and oxidation resistance to 1000 °C, which is 400 °C higher than the operating temperature limit of conventional titanium alloys. [ not specific enough to verify ] [ 3 ]
General Electric uses gamma TiAl for the low-pressure turbine blades on its GEnx engine, which powers the Boeing 787 and Boeing 747-8 aircraft. This was the first large-scale use of this material on a commercial jet engine [ 4 ] when it entered service in 2011. [ 5 ] The TiAl LPT blades are cast by Precision Castparts Corp. and Avio s.p.a. Machining of the Stage 6, and Stage 7 LPT blades is performed by Moeller Manufacturing. [ 6 ] [ citation needed ] An alternate pathway for production of the gamma TiAl blades for the GEnx and GE9x engines using additive manufacturing is being explored. [ 7 ]
In 2019 a new 55 g lightweight version of the Omega Seamaster wristwatch was made, using gamma titanium aluminide for the case, backcase and crown, and a titanium dial and mechanism in Ti 6/4 (grade 5). The retail price of this watch at £37,240 was nine times that of the basic Seamaster and comparable to the top of the range platinum-cased version with a moonphase complication . [ 8 ]
Alpha 2-Ti₃Al is an intermetallic compound of titanium and aluminum, belonging to the Ti-Al system of advanced high-temperature materials. It is primarily used in aerospace and other high-performance applications due to its balance of strength, lightweight properties, and oxidation resistance.
It has an ordered hexagonal (D0₁₉) crystal structure, which makes it distinct from the more commonly known γ-TiAl (gamma titanium aluminide).
Higher strength than conventional titanium alloys, especially at high temperatures. More brittle than pure titanium but tougher than γ-TiAl, making it useful in applications requiring a trade-off between toughness and lightweight properties.
Improved high-temperature oxidation resistance compared to pure titanium, but generally not as good as γ-TiAl or other high-temperature alloys like nickel-based superalloys. Often used with coatings to further enhance oxidation resistance.
Density and Lightweight Properties:
Lower density than traditional nickel-based superalloys, making it attractive for aerospace applications where weight reduction is crucial.
Operates effectively at 600–800°C, making it useful in jet engines, turbine components, and hypersonic vehicles.
Applications of Alpha 2-Ti₃Al:
Aerospace: Used in jet engine components, compressor blades, and airframe structures where high strength and lightweight properties are needed.
Automotive (High-Performance Vehicles): Some high-end applications in racing engines. Military and Defense: Structural components in hypersonic aircraft and advanced missiles.
Energy Sector : Potential use in turbine components for power generation.
Challenges and Limitations:
Brittleness : More brittle than conventional titanium alloys, requiring careful processing and potential use of composite materials.
Manufacturing Complexity: Difficult to process and fabricate due to its intermetallic nature, often requiring advanced techniques like powder metallurgy, additive manufacturing, or specialized forging methods.
Oxidation Resistance: While better than standard titanium, it still requires protective coatings for long-term use in extreme environments.
TiAl 3 has the lowest density of 3.4 g/cm 3 , the highest micro hardness of 465–670 kg/mm 2 and the best oxidation resistance even at 1 000 °C. However, the applications of TiAl 3 in the engineering and aerospace fields are limited by its poor ductility. In addition, the loss of ductility at ambient temperature is usually accompanied by a change of fracture mode from ductile transgranular to brittle intergranular or to brittle cleavage. Despite the fact that a lot of toughening strategies have been developed to improve their toughness, machining quality is still a difficult problem to tackle. Near-net shape manufacturing technology is considered as one of the best choices for preparing such materials. {date=July 2022} [ citation needed ] | https://en.wikipedia.org/wiki/Titanium_aluminide |
Titanium carbonitride ( TiCN ) is harder than titanium nitride (TiN) and it can be used without lubrication. Titanium carbonitride is applied to machine tool cutters by vapor deposition . [ 1 ] [ 2 ]
Titanium carbonitride coatings have high hardness and wear resistance. Titanium carbonitride is a cermet —a composite of metal and ceramic. The ceramic provides high hardness , and the metal provides toughness . [ 3 ]
Titanium carbonitride can be prepared by reacting titanium dioxide and carbon in a furnace containing an inert gas, then reducing in nitrogen gas. [ 4 ]
This metalworking article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Titanium_carbonitride |
Titanium foams exhibit high specific strength, high energy absorption, excellent corrosion resistance and biocompatibility . These materials are ideally suited for applications within the aerospace industry. [ 1 ] [ 2 ] [ 3 ] An inherent resistance to corrosion allows the foam to be a desirable candidate for various filtering applications. [ 4 ] [ 5 ] Further, titanium's physiological inertness makes its porous form a promising candidate for biomedical implantation devices. [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 11 ] The largest advantage in fabricating titanium foams is that the mechanical and functional properties can be adjusted through manufacturing manipulations that vary porosity and cell morphology. The high appeal of titanium foams is directly correlated to a multi-industry demand for advancement in this technology.
Banhart [ 12 ] describes two dominating perspectives in which cellular metals are characterized, referring to them as atomistic and macroscopic. The atomistic (or molecular) perspective holds that a cellular material is a construction of struts, membranes, and other elements which possess mechanical properties of their bulk metal counterpart. Indeed, the physical, mechanical, and thermal properties of titanium foams are commonly measured using the same methods as that of their solid counterparts. However, special precautions must be taken due to the cellular structure of metal foams. [ 13 ] From a macroscopic perspective, the cellular structure is perceived as a homogeneous structure and characterized by considering the effective (or averaged) material parameters. [ 12 ]
Titanium foams are characterized structurally by their pore topology (relative percentage of open vs. closed pores), porosity (the multiplicative inverse of relative density), pore size and shape, and anisotropy. [ 13 ] Microstructures are most often examined by optical microscopy , [ 14 ] scanning electron microscopy [ 15 ] and X-ray tomography . [ 16 ]
Categorizing titanium foams in terms of pore structure (as either open- or close-celled) is the most basic form of differentiation. In close-celled foams, pores are composed of bubbles entrapped in the metallic solid. These foams consist of a continuous network of sealed pores wherein interconnections between the pores are virtually non-existent. Alternatively, in open-celled foams, the pores are interconnected and solid struts allow fluid to pass through. [ 17 ]
Most manufactured foams contain both types of pores, although in many cases the subtype is minimal. [ 18 ] According to the IUPAC , pore sizes are classified into three categories: micro (less than 2 nm), meso (between 2 and 50 nm) and macro (larger than 50 nm) pores. [ 18 ]
As with other metal foams, the properties of titanium foams depend mostly on the properties of the starting material and the relative density of the resultant foam. Thermal properties in foams – such as melting point, specific heat and expansion coefficient – remain constant for both the foams and the metals from which they are composed. However, the mechanical properties of foams are greatly influenced by microstructure , which include the aforementioned properties as well as anisotropy and defects within the foam's structure. [ 19 ]
The mechanical properties of titanium foams are sensitive to the presence of interstitial solutes, which present limitations to processing routes and utilization. Titanium has a high affinity for atmospheric gases . In foams, this is evidenced by the metal's tendency to trap oxides within cell edges. [ 20 ] [ 21 ] [ 22 ] Micro-hardness of cell walls, elastic modulus , and yield strength increase as a result of interstitial solutes; ductility , which is a function of the quantity of interstitial impurities, is consequently reduced. [ 23 ] Of the atmospheric gases, nitrogen has the most significant impact, followed by oxygen and carbon. [ 24 ] These impurities are often present in the precursor mixture and also introduced during processing.
Gibson & Ashby [ 17 ] micromechanical models for porous materials provide mathematical equations for the prediction of mechanical parameters based on experimentally determined geometric constants. The constants of proportionality are determined by fitting experimental data to various mathematical models for structures consisting of cubes and solid struts and are dependent upon cell geometry. A limitation of the Gibson & Ashby [ 17 ] model is that it is most accurate for foams exhibiting porosities higher than 70%, although experimental comparisons for lower porosity foams have shown agreement with this model. Ye & Dunand found reasonable agreement to the Gibson & Ashby model for titanium foams exhibiting 42% porosity. Ultrasonic measurements provided an average Young's modulus value of 39 GPa, which is in relatively good agreement with the Gibson & Ashby prediction of 35 GPa. [ 15 ]
The Gibson & Ashby [ 17 ] models assume ideal structures; microstructural irregularities (e.g. inhomogeneous pore distribution; defects) are not considered. Additionally, experimental results from which the predetermined proportionality constants were based on experimental values that were obtained from simple compression tests. Consequently, they may not be applicable for multiaxial loads. [ 25 ]
Minimum solid area models assume that the load bearing area (cross-sectional area normal to the stress) is the logical basis for modeling mechanical behavior. MSA models assume pore interaction results in reduction of stress. Therefore, the minimum solid areas are the carriers of stress. As a result, predicted mechanical properties fluctuate based on the quantification of the solid area of the foam. For titanium foams consisting of partially sintered powders, the minimum solid area consists of the neck area between powders through the cross-section of cell walls between macropores. [ 26 ] The mathematical relationships in MSA models [ 27 ] are relatively consistent with the Gibson & Ashby model. [ 17 ] [ 28 ] However, the MSA models are designed to predict mechanical property parameters over a broader range of porosity levels. Like the Gibson & Ashby models, MSA models were derived assuming idealized (defect-free) structures containing uniform pore shapes, size and distribution.
The most frequently reported mechanical property of titanium foams is compressive strength. [ 29 ] It was generally accepted that the compressive properties of metal foams depended on the properties of the cell wall rather than on pore size. However, more recent research has indicated that smaller pore sizes equate to higher compressive strength. As pore sizes reach nano-dimensions, the relationship is even more clear due to changes in deformation mechanism. [ 30 ]
Tuncer & Arslan fabricated titanium foams via the space-holder method using various shaped space-holders to elucidate the effect of cell morphology on mechanical properties. They found that foams created with needle-like urea space-holders exhibited a decrease in elastic modulus and yield strength when compared to spherical pores. [ 31 ]
Many metal foam manufacturing techniques are accomplished by the introduction of a gaseous phase into a precursor matrix, which can occur in either molten metal or a powdered metal form. Due to titanium's high melting point (1670 °C) and high chemical affinity with oxygen, nitrogen, carbon and hydrogen (which dissolve rapidly either in liquid or solid titanium at a temperature above 400 °C [ 21 ] ), solid-state processes based on powder densification are the preferred method of fabrication. [ 15 ] [ 21 ] [ 26 ] [ 29 ] [ 32 ] [ 33 ] Processing methods must also be designed to avoid exposure to air or moisture; vacuum or inert gas sintering processes are usually sufficient for preventing contamination. [ 21 ] [ 34 ]
Utilizing powder metallurgy routes [ 35 ] for titanium foam fabrication allows for production at lower temperatures than those required through a melt process and reduces overall risks for contamination. In loose-powder sintering (also known as gravity sintering), pores are created through diffusion bonding arising from the voids existing between packed powder particles. Axial compaction followed by sintering follows the same procedure as above, but pressures is applied for compaction of the precursor material. [ 36 ] For both compaction methods, the resulting pore morphology is dependent upon the morphology of the metallic powder, making it difficult to control the size, shape, and distribution of the pores. [ 35 ] Another disadvantage includes the relatively high probability of pore collapse and limited achievable porosity levels. [ 37 ]
To produce titanium foams via expansion of pressurized gas, the titanium precursor mixture is placed within a gas-tight metal can, which is evacuated after filling. The metal can is pressurized with inert gas—most commonly argon – and is pressed isostatically. The gas-filled pores are contained within the compacted matrix, and upon exposure to elevated temperatures, these bubbles expand through creep of the surrounding metal matrix. [ 38 ] Since processing titanium foams using hot isostatic pressing (HIP) eliminates the need for separate compaction and sintering processes, a wider variety of custom shapes and sizes are possible than via loose powder sintering techniques. [ 39 ] Disadvantages of this process include reduced pore connectivity, limited achievable porosity, and a complicated experimental set-up. [ 39 ] However, a unique aspect of the HIP process with respect to titanium (and other polymorphic materials) is that transformation superplasticity can be enhanced through the HIP process by way of thermal cycling, or by cycling around the alpha/beta allotropic temperature boundaries of the metal. [ 32 ]
Titanium undergoes allotropic transformation from its α-phase (hexagonal close-packed (hcp) structure at temperatures less than 882.5 °C) to its β-phase (body centered cubic, bcc) structure at temperatures above 882.3 °C). Alpha-phase titanium products typically exhibit medium to high strength with excellent creep strength, whereas beta-phase titanium products typically exhibit very high strength and low ductility. [ 32 ] [ 36 ] Foams created under thermal cycling conditions have been shown to exhibit increased porosity due to the density difference between allotropic phases. Davis et al. produced titanium foams with 41% porosity (as compared to 27% porosity through the normal HIP creep mechanism). [ 32 ] Increases in overall ductility were also observed in foams created through thermal cycling. In a similar experiment, porosity of 44% was achieved and determined as the maximum achievable porosity under thermal cycling conditions. [ 40 ] A later study also utilized exploitation of transformation superplasticity conditions through HIP, but in this case, the titanium powder in the precursor matrix was replaced with titanium wires to create anisotropic pores. The resulting anisotropic pores showed closer correlation with natural bone in that the foams exhibited higher elastic moduli, yield strength and deformation when subjected to longitudinally loaded forces than when loads were applied transversely. [ 41 ]
The space-holder technique is the most commonly employed method for producing titanium foams. The space-holder technique allows for the fabrication of higher porosity foams (35–80% [ 42 ] ) than other techniques, while also giving the engineer more control over pore fraction, shape and connectivity. [ 38 ] Mechanical properties can be adjusted through the size, shape and quantity of space-holders employed. The space-holder technique was first demonstrated by Zhao and Sun [ 43 ] for the fabrication of aluminum foams in a powder metallurgical method, which consisted of the incorporation of NaCl as a space-holder. The space-holder was mixed into the powder mixture and dissolved prior to sintering. The same method was used to create titanium foams for the first time when Wen et al. utilized ammonium hydrogen carbonate spacers. [ 44 ]
The size and shape of the metal powder has a direct impact on the stability of the precursor as well as the resulting foam. For this purpose, powders that increase packing efficiency are most advantageous. [ 31 ] The use of spherical particles may result in less contact of particles which consequently leads to larger secondary pores and a higher probability of pore collapse prior to complete sintering. [ 45 ] This factor can be limited through different compaction techniques that decrease the degree of interstitial sites around the titanium particles. However, this method also has limitations; for example, the powders cannot be compacted to such a degree that would promote deformation of the spacer (unless anisotropic pore shape is desired). [ 15 ] [ 46 ]
The selection of the space-holder is one of the most crucial steps because it defines many of the properties of the resulting foam, including cell shape, cell size and macroporosity. The space-holder should be inert and represent the size and shape of the desired pores. The porosity may be adjusted anywhere between 50 and 85% without the filler material becoming a part of the resultant foam. [ 10 ] It is also important to select a spacer that has limited or no solubility in titanium, as this incorporation will affect the mechanical properties of the resulting foam. [ 47 ]
The degree of homogeneity in pore distribution of the final product is primarily dependent on the adequacy of mixing of the precursor. The difference in particle size between the titanium powders and the spacers directly impacts the ability to adequately mix the preform. The greater the size difference, the more difficult it is to control this process. [ 47 ] Nonhomogeneous mixing resulting from the use of spacers considerably larger than the titanium particles employed and has shown adverse effects in the stability of the precursor after removal of spacer and in the distribution of porosity. [ 31 ] [ 48 ] Spacer size has been investigated. [ 31 ] [ 39 ] [ 49 ] It was shown that the use of a coarse spacer results in thicker pore walls while the use of finer spacers results in enhanced compaction, leading to increased densification. Increased densification is evidenced by a monomodal pore distribution with the employment of fine spacers and a bimodal distribution using coarse spacers. Further, finer spacers result in a more homogeneous pore distribution. Sharma et al. [ 50 ] utilized acicular spacers and achieved porosities up to 60% where pores were undistorted. In samples employing fine particles, porosities up to 70% were achievable before noting distortion in the pores. [ 49 ] However, the bimodal pore distribution observed in coarse-spacer samples showed to be beneficial in terms of mechanical properties in that higher compressive strengths were observed, beyond those that might exist due to the inverse relationship of porosity and compressive strength alone. [ 49 ]
The precursor mixture of powders and space-holders are compacted into a mold under a specified pressure. This can be achieved through uniaxial or isostatic processes. The pores resulting from this method are open and interconnected via windows between neighboring pores with the size of the pores partially dependent upon the coordination number and contact area of the resulting compact. Compaction pressure must be high enough to ensure sufficient mechanical strength for retention of pore geometry specified by the space-holder, but not too high enough as to cause deformation of the space-holder. [ 47 ]
When employing dissolvable spacers, it is possible to remove the spacer after sintering, which reduces the risk of pore collapse.
In most cases, foams created using space-holders contain bimodal pore distributions with macro-sized pores resulting from the space-holder particles and micro-sized pores located on the pore walls and resulting from incomplete sintering of the powder matrix. As a result, the macropores typically exhibit rough internal surfaces. [ 51 ] In some applications, such as for the use of bio-medical implants, this is an advantageous property. Inner porosity (or micro-porosity) has been shown to reduce stiffness; thus, reduce the risk of stress-shielding effects, while also offering improved osseointegration. [ 14 ] [ 50 ] [ 51 ]
Sodium chloride is the most commonly chosen space-holder for titanium foams because it is highly soluble in water and inert with respect to titanium. This inertness prevents contamination and degradation of the mechanical properties of the resulting foam. Moreover, NaCl is non-toxic; any residuals are bioinert. [ 50 ] [ 52 ]
Bansiddhi & Dunand pioneered the use of NaCl as a permanent space-holder for the fabrication of NiTi foams. [ 53 ] The resulting foams consisted of 32-36% porosity with more complete densification than they observed when producing NiTi foams using a sodium fluoride (NaF) space-holder. [ 54 ] However, processing parameters resulted in molten NaCl and a metal/salt blend in the cavities of the foam. Certain risks are associated with using a molten space-holder including reaction with the metal, dissolving of the space-holder in the metal and prevention of densification through the creation of a thin layer of liquid between the metal and particles. [ 51 ] Near complete densification was achieved when NaCl was used as a permanent space-holder in pure titanium foam. [ 15 ] In this case, a temperature below the melting point of NaCl was used; titanium is less creep resistant than NiTi, which allows for densification at lower temperatures. The resulting foams achieved porosity of 50–67% with minimal observable microporosity. Anisotropic pore shape in some areas alluded to NaCl's deformation during HIP, which is desirable for some applications. [ 55 ] Additionally, an observed, rough inner surface of the pores holds advantages for biomedical implant applications.
Jha et al. [ 45 ] achieved 65-80% porosity through the use of NaCl as a space-holder and a cold compaction process at various pressures with two-stage sintering. In this case, NaCl was removed through dissolution after the second stage of sintering. Resulting Young's moduli (8–15 GPa) were considerably lower than the Young's modulus of 29 GPa achieved for 50% porosity foams. [ 23 ] [ 55 ] This illustrates the known relationship between porosity and Young's modulus wherein Young's modulus decreases linearly with increasing porosity. Achievable porosity through the space-holder method is directly related to the type and amount of space-holder utilized (up to a threshold maximum achievable porosity level).
Magnesium can be removed either thermally or by reactive measures through the dissolution in acid. [ 26 ] [ 56 ] [ 57 ] Esen & Bor [ 26 ] found a critical content of magnesium as a space holder to be 55-60%, above which compacts shrink excessively during sintering. Foams ranging in porosity from 45 to 70% with a bimodal pore distribution and compressive strength of 15 MPa (for 70% porosity) were demonstrated. Kim et al. fabricated foams with anisotropic pores through the intentional deformation of Mg particles during compaction in an effort to enhance mechanical properties. A final porosity of 70% equated to a yield strength of 38 MPa for normal orientation of pores and 59 MPa when pores were aligned with the direction of compression. [ 57 ]
Another commonly employed space-holder for titanium foams is urea , which yielded porosities from 20 to 75%. [ 31 ] [ 50 ] [ 58 ] [ 49 ] [ 44 ] Wen et al. [ 44 ] produced foams exhibiting a bimodal pore distribution with porosities ranging from 55 to 75%, Young's moduli between 3–6.4 GPa, and a plateau stress of 10–35 MPa. An inverse relationship between plateau stress and porosity was observed with increased porosity resulting in decreased plateau stress. [ 44 ] Tuncer et al. utilized urea in combination with irregularly shaped titanium powders in an effort to increase green strength through increased packing efficiency (of particles). This also eliminated the need for the incorporation of a binder. [ 58 ]
Tapioca starch can be burnt off easily through the sintering process and is insoluble in titanium. Titanium foams consisting of a bimodal pore distribution (macropores ranging from 100 to 300 μm) and 64–79% porosity, exhibited yield strengths of 23–41 MPa and Young's moduli of 1.6–3.7 GPa. [ 59 ]
Although ammonium bicarbonate has been utilized in the manufacturing of titanium foams, [ 44 ] it is not an ideal spacer in that it has a low melting/dissociation point and some solubility in titanium. This results in considerable shrinkage which makes control of pore shape difficult. Furthermore, the decomposition releases environmentally harmful gases. [ 60 ]
Freeze-casting is a directional solidification technique that is utilized to fabricate materials exhibiting anisotropic, elongated pore structures. [ 61 ] Pore morphology is defined, in large part, by the morphology of the solidified fluid.
Titanium foams exhibiting dendritic [ 62 ] [ 63 ] and lamellar [ 64 ] pore structures have been produced, through the use of non-aqueous and aqueous processing respectively. These materials exhibit anisotropic mechanical properties as a result of their anisotropic pore structures. Compressive strength for loads applied parallel to the wall direction of titanium foams are found to be, on average, 2.5 times greater than for those applied perpendicular to the wall direction. [ 61 ]
Potential structural applications for titanium foams include their general incorporation into light-weight structures and as components for mechanical energy absorption. The most important considerations for the use of titanium foams in structural applications includes their porosity, specific strength, ductility in compression and cost. Because of low manufacturing costs, most metal foams marketed for structural applications are of a close-celled aluminum variety. [ 65 ] In comparison, titanium foam manufacturing incurs a higher cost, but this cost is defensible in space applications where the material offers an otherwise incomparable reduction in overall weight. The lower thermal conductivity of titanium may also be appreciated in rocket construction. [ 1 ] The specific strength, overall energy absorbing capability and high melting point all reinforce titanium's superiority to aluminum in aerospace and military applications. [ 3 ] When used for aerospace applications, levels of porosity close to 90% are desired. [ 52 ] Titanium foams are capable of retaining their high tensile strength at temperatures up to 400 °C; a limit imposed by the metal's low resistance to oxidation. [ 36 ]
The driving force for titanium foam's replacement of existing materials in the aerospace sector results from the following five factors: [ 36 ]
The most urgent problem of engineering and its advanced branch of aerospace engineering is the efficient use of materials as well as increased service life. [ 1 ]
Sandwich panel cores are used throughout the aerospace industry; they are integrated within aircraft bodies, floors and internal panels. Sandwich constructions consist of two faces separated by a thick, light-weight core and are most commonly composed of balsa-wood, foamed polymers, glue-bonded aluminum or Nomex (paper) honeycombs. Typically, the cores are combined with reinforcing fibers to increase their shear modulus. [ 66 ] Indeed, carbon fiber-reinforced polymers exhibit the highest specific stiffness and strength of these materials. [ 67 ] [ 68 ] However, polymers decompose at low temperatures; thus employment of the aforementioned materials pose inherent challenges due to the limited range of temperature they may be utilized within as well as their moisture-dependent properties. [ 13 ] The largest and most inadequately predicted failure within the core results from strain localization. Strain localization refers to the development of bands exhibiting intensive straining as a result of the localization of deformations in the solid. [ 69 ] [ 70 ] For the best performance, the structure should exhibit low peak response force and high total energy absorption. [ 18 ] Titanium foams are lightweight, stiff, and possess the capability to resist blast. Furthermore, the use of titanium-based foams exhibiting homogeneous porosity distribution would significantly decrease the risks associated with strain localization. The high strength-to-weight ratio of titanium foams offers an opportunity to provide increased bending and shearing stiffness as well as energy absorption capabilities during periods of bending. [ 66 ] [ 70 ] [ 71 ] Titanium foams may be utilized in environments with elevated temperatures (up to 400 °C). Composite structures may also be produced; the incorporation of silicon carbide monofilaments into Ti-6-Al-4V foams was shown to exhibit an elastic modulus of 195 GPa and tensile strength of 800 MPa. [ 72 ]
Titanium foams exhibiting auxetic pore structures are of interest for incorporation in sandwich panel cores due to their enhanced shear performance. [ 73 ] [ 74 ] Foams with this pore structure exhibit negative Poisson's ratio in one or more dimensions. [ 66 ] Poisson's ratio is defined as the ratio of the lateral contractile strain to the longitudinal tensile strain for the foam undergoing uniaxial tension in the loading direction. [ 75 ] Auxetic materials are typically able to resist indentations through their response to compression; upon compression, the auxetic material contracts. [ 75 ] In addition to indentation resistance, research has shown that auxetic foams offer better absorption of sound and vibration, enhanced shear resistance and facture toughness. These structures also exhibit synclastic bending, which results lends itself to integration within curved sandwich panels.
Titanium alloys are the choice material for a diverse range of biomedical implants. [ 76 ] Currently employed titanium alloy implants include: hip joints, [ 77 ] bone screws, [ 9 ] [ 78 ] knee joints, [ 51 ] spinal fusions, [ 8 ] shoulder joints, [ 51 ] and bone plates. [ 76 ] [ 79 ] [ 80 ] These alloys range from high ductility, commercially-pure titanium foams with high formability, to heat-treatable alloys with high strength. Titanium is well-suited for use in magnetic resonance imaging (MRI) and computed tomography (CT), [ 81 ] [ 82 ] which further enhances its applicability for biomedical implant applications.
Biomedical implants should have low density for patient comfort and high porosity and surface area to facilitate vascularization and the ingrowth of new bone. [ 83 ] Ideally, the implant will allow sufficiently easy fluid flow for cell nutrition and osteoblast multiplication as well as migration for cellular colonization of the implant to become uniform. The pores contained within the foam's cellular matrix mimic the extracellular matrix of bone, allowing the body to fixate with the implant. The porosity of the implant also promotes apposition and facilitates vascularization−as cells are able to attach, reproduce and form basic functions. [ 84 ] It has been shown that a macropore size of 200–500 μm is preferred for ingrowths of new bone tissues and transportation of body fluids. The lower bound is controlled by the size of cells (~20 μm), and the upper bound is related to the specific surface area through the availability of binding sites. [ 84 ] Finer pores further help in tissue growth and biofluid movement. [ 85 ] Anisotropic, elongated pores (such as those attainable via the freeze-casting technique) may be beneficial in bone implants in that they can further mimic the structure of bone.
The porous surface geometry of the foam promotes bone in-growth, provides anchorage for fixation, and ensures stresses are transferred from the implant to the bone. [ 86 ] Surface roughness in the pore can enhance bone in-growth, and coarser cell size facilitates faster tissue growth. [ 55 ] To optimize the implant's functionality and ability to successfully fuse with bone, it may be necessary to manipulate the material's manufacturing methods in order to modify the foam's pore structure. Changes in pore structure can directly influence implant strength as well as other key properties.
Human cancellous bone possesses a stiffness ranging from 12 to 23 GPa; [ 87 ] careful control and modification of manufacturing parameters to achieve similar strengths is imperative for practicality of integration. [ 88 ] Correctly predicting the Young's modulus for foams is imperative for actual biomedical integration; a mismatch of Young's moduli between the implant and the bone can result in stress-shielding effects from a disproportional handling of stress. [ 89 ] The implant which typically exhibits a higher Young's modulus than the bone will absorb most of the load. As a result of this imbalance, the starting bone density will be reduced, there will be tissue death and, eventually, implant failure. [ 90 ]
Natural bone exhibits the ability to adjust local fiber away from the low-stress regions toward high stress regions through the distribution of porosity, thus maximizing overall comfort. [ 91 ] Using finite element analysis, researchers examined the effect of filling pores with bone on mechanical properties. [ 90 ] They concluded that bone ingrowth significantly improved the mechanical properties, evidenced by decreased localized plasticity and stress concentrations. In effect, the titanium foam in the study allowed the bone to exhibit its natural ability to adjust local fiber away from the low-stress regions toward high stress regions.
Experiments demonstrated that random combinations of pore size and shape result in lower Young's moduli. Theoretical models for the quantification of Young's moduli do not account for random pore size and shape distribution, so experimental measurements must be conducted in the presence of heterogeneous pore size and distribution. This is a limitation of the micro-mechanical models discussed above.
Currently utilized implants take a great deal of time to integrate with the body after the initial surgical procedure occurs. True adhesion between the implant and the bone has been difficult to achieve and, unfortunately, success rates of implant fixation are low due to the implant's failure to achieve long-term osseointegration into the bone. [ 48 ] [ 51 ] [ 92 ] With an increasing number of individuals requiring orthopedic implants, [ 11 ] the development of materials with structural and biological potential to improve osseointegration is crucial. Utilization of titanium-based foams present one way to potentially improve the bioactivity [ 6 ] [ 93 ] [ 94 ] [ 95 ] and reduce stress-shielding effects of currently employed bioimplant materials.
The problem of osseointegration is best understood by examining the process of natural bone growth. In the body, bone and tissues experience self-regeneration, and structural modifications occur normally in response to environmental stimuli. [ 96 ] Successful osseointegration occurs in three main stages that follow a natural biologically determined procedure: 1) incorporation of the implant into the bone's formation, 2) adaption of the new bone mass to carry weight and 3) remodeling of the new bone structure. The first stage in this process is the most crucial for overall success; [ 97 ] the implant and the bone must form a rapid connection, and this bond must be strong and enduring. Owing to its porous structure, a titanium metal foam implant may be able to achieve close fixation with the bone and will decrease patient recovery time considerably. Essentially, the foam becomes an extracellular matrix in the body as tissue is integrated into it. [ 84 ] Today, the implants most commonly used for bone replacement lack the ability to promote these characteristics, which are found in natural bone and, as a result, the implants have limited lifetimes. [ 84 ] This phenomenon of osseointegration works similarly to direct fracture healing. However, instead of a bone fragment-end reconnecting to bone, the fragment-end connects to an implant surface. [ 97 ] In a study on fibroblastic interactions with high-porosity Ti6Al4V alloy, the metal foam was supportive of cell attachment and proliferation, migration through the porous network, and proved capable of sustaining a large cell population. [ 7 ]
Titanium's propensity to form an oxide layer on its surface prevents corrosion of surfaces that are in contact with human tissues because the surface oxides minimize diffusion of metal ions from the bulk material to the surface. [ 89 ] When titanium gains a coating to make it more bioactive, it can turn the already biocompatible titanium surface into an interface able to enhance osteoblast adhesion and able to promote osseointegration. [ 90 ] Today, research is heavily focused on improving the success rate of integration and uses an understanding of the natural process of bone growth and repair to create coatings that will enhance the surface finish and surface properties of the implant. These adjustments allow the artificial structure to mimic biological materials and to gain acceptance into the body with fewer negative side effects. [ 98 ] [ 99 ] A 3-year clinical and radiographic study found implants in humans coated by nanocrystalline hydroxylapatite (HA) to support osseointegration. The nanocrystalline HA was developed with a large rough surface of interconnecting pores between 10 and 20 nm of the silica matrix gel, resulting in a porous bone structure. Mean rates of marginal bone loss were insignificant and the periotest values were indicative of a solid osseointegration. [ 100 ] In effect, the pores are structured in such a way that they are able hold onto the proteins on the biomaterial's surface. Ideally, this allows the body to engage in self-repair in that the synthetic HA is recognized as a like-nanomaterial in which live tissues may develop [ 10 ]
Titanium foams can be coated with HA through various methods including plasma spraying, sol-gel and electrophoretic deposition. It has been shown that HA-coated titanium exhibits increased interfacial strength in comparison to titanium foams without the coating. In an effort to enhance bone in-growth, Spoerke et al. developed a method for growing organoapatites on titanium implants. Organoapatites may assist in-bone in-growth at the implant interface. The foams were manufactured using a modified HIP process, which exploits the allotropic nature of titanium to create higher porosity foams. Previous in vitro experimentation with the organoapatite-titanium foam held promising results including the possibility that ingrown tissue within these coated pores will improve the lifetime use of the foam through reduction of stress-shielding effects. [ 41 ]
In the lab, synthetic nanocrystalline bone grafting material in mice has shown in-growth of vascularized fibrous tissue which resulted in improved healing. Furthermore, new blood vessels were observed at day 5 after implantation, and the implant showed a high functional vessel density. [ 85 ] In a study examining the femoral epiphyses of rabbits in two to eight weeks of healing, bone-to-implant contact was compared to bone growth inside the chambers for four different implant surfaces. The researchers found that bone substitute materials may improve the bone apposition onto titanium. [ 101 ] | https://en.wikipedia.org/wiki/Titanium_foam |
Titanium hydride normally refers to the inorganic compound TiH 2 and related nonstoichiometric materials. [ 1 ] [ 2 ] It is commercially available as a stable grey/black powder, which is used as an additive in the production of Alnico sintered magnets, in the sintering of powdered metals, the production of metal foam , the production of powdered titanium metal and in pyrotechnics. [ 3 ]
Also known as titanium–hydrogen alloy , [ 4 ] [ 5 ] it is an alloy [ 6 ] of titanium , hydrogen , and possibly other elements. When hydrogen is the main alloying element, its content in the titanium hydride is between 0.02% and 4.0% by weight. Alloying elements intentionally added to modify the characteristics of titanium hydride include gallium , iron , vanadium , and aluminium .
In the commercial process for producing non-stoichiometric TiH 2− x , titanium metal sponge is treated with hydrogen gas at atmospheric pressure at between 300-500 °C. Absorption of hydrogen is exothermic and rapid, changing the color of the sponge grey/black. The brittle product is ground to a powder, which has a composition around TiH 1.95 . [ 3 ] In the laboratory, titanium hydride is produced by heating titanium powder under flowing hydrogen at 700 °C, the idealized equation being: [ 7 ]
Other methods of producing titanium hydride include electrochemical and ball milling methods. [ 8 ] [ 9 ]
TiH 1.95 is unaffected by water and air. [ citation needed ] It is slowly attacked by strong acids and is degraded by hydrofluoric and hot sulfuric acids. It reacts rapidly with oxidizing agents, this reactivity leading to the use of titanium hydride in pyrotechnics. [ 3 ]
The material has been used to produce highly pure hydrogen, which is released upon heating the solid. [ 7 ] Hydrogen release in TiH ~2 starts just above 400 °C but may not be complete until the melting point of titanium metal. [ 10 ] [ 3 ] Titanium tritide (Ti 3 H x ) has been proposed for long-term storage of tritium gas. [ 11 ]
As TiH x approaches stoichiometry, it adopts a distorted body-centered tetragonal structure, termed the ε-form with an axial ratio of less than 1. This composition is very unstable with respect to partial thermal decomposition, unless maintained under a pure hydrogen atmosphere. Otherwise, the composition rapidly decomposes at room temperature until an approximate composition of TiH 1.74 is reached. [ citation needed ] This composition adopts the fluorite structure, and is termed the δ-form, and only very slowly thermally decomposing at room temperature until an approximate composition of TiH 1.47 is reached, at which point, inclusions of the hexagonal close packed α-form, which is the same form as pure titanium, begin to appear.
The evolution of the dihydride from titanium metal and hydrogen has been examined in some detail. α-Titanium has a hexagonal close packed (hcp) structure at room temperature. Hydrogen initially occupies tetrahedral interstitial sites in the titanium. As the H/Ti ratio approaches 2, the material adopts the β-form to a face centred cubic (fcc) , δ-form, the H atoms eventually filling all the tetrahedral sites to give the limiting stoichiometry of TiH 2 . The various phases are described in the table below.
If titanium hydride contains 4.0% hydrogen at less than around 40 °C then it transforms into a body-centred tetragonal (bct) structure called ε-titanium. [ 12 ]
When titanium hydrides with less than 1.3% hydrogen, known as hypoeutectoid titanium hydride are cooled, the β-titanium phase of the mixture attempts to revert to the α-titanium phase, resulting in an excess of hydrogen. One way for hydrogen to leave the β-titanium phase is for the titanium to partially transform into δ-titanium, leaving behind titanium that is low enough in hydrogen to take the form of α-titanium, resulting in an α-titanium matrix with δ-titanium inclusions.
A metastable γ-titanium hydride phase has been reported. [ 13 ] When α-titanium hydride with a hydrogen content of 0.02-0.06% is quenched rapidly, it forms into γ-titanium hydride, as the atoms "freeze" in place when the cell structure changes from hcp to fcc. γ-Titanium takes a body centred tetragonal (bct) structure. Moreover, there is no compositional change so the atoms generally retain their same neighbours.
The absorption of hydrogen and the formation of titanium hydride are a source of damage to titanium and titanium alloys. This hydrogen embrittlement process is of particular concern when titanium and alloys are used as structural materials, as in nuclear reactors.
Hydrogen embrittlement manifests as a reduction in ductility and eventually spalling of titanium surfaces. The effect of hydrogen is to a large extent determined by the composition, metallurgical history and handling of the Ti and Ti alloy. [ 14 ] CP-titanium ( commercially pure : ≤99.55% Ti content) is more susceptible to hydrogen attack than pure α-titanium. Embrittlement, observed as a reduction in ductility and caused by the formation of a solid solution of hydrogen, can occur in CP-titanium at concentrations as low as 30-40 ppm. Hydride formation has been linked to the presence of iron in the surface of a Ti alloy. Hydride particles are observed in specimens of Ti and Ti alloys that have been welded, and because of this welding is often carried out under an inert gas shield to reduce the possibility of hydride formation. [ 14 ]
Ti and Ti alloys form a surface oxide layer , composed of a mixture of Ti(II) , Ti(III) and Ti(IV) oxides, [ 15 ] which offers a degree of protection to hydrogen entering the bulk. [ 14 ] The thickness of this can be increased by anodizing , a process which also results in a distinctive colouration of the material. Ti and Ti alloys are often used in hydrogen containing environments and in conditions where hydrogen is reduced electrolytically on the surface. Pickling , an acid bath treatment which is used to clean the surface can be a source of hydrogen.
Common applications include ceramics , pyrotechnics , sports equipment , as a laboratory reagent , as a blowing agent , and as a precursor to porous titanium. When heated as a mixture with other metals in powder metallurgy , titanium hydride releases hydrogen which serves to remove carbon and oxygen, producing a strong alloy. [ 3 ]
The density of titanium hydride varies based on the alloying constituents, but for pure titanium hydride it ranges between 3.76 and 4.51 g/cm 3 .
Even in the narrow range of concentrations that make up titanium hydride, mixtures of hydrogen and titanium can form a number of different structures, with very different properties. Understanding such properties is essential to making quality titanium hydride. At room temperature , the most stable form of titanium is the hexagonal close-packed (HCP) structure α-titanium. It is a fairly hard metal that can dissolve only a small concentration of hydrogen, no more than 0.20 wt% at 464 °C (867 °F), and only 0.02% at 25 °C (77 °F). If titanium hydride contains more than 0.20% hydrogen at titanium hydride-making temperatures it transforms into a body-centred cubic (BCC) structure called β-titanium. It can dissolve considerably more hydrogen, more than 2.1% hydrogen at 636 °C (1,177 °F). If titanium hydride contains more than 2.1% at 636 °C (1,177 °F) then it transforms into a face-centred cubic (FCC) structure called δ-titanium. It can dissolve even more hydrogen, as much as 4.0% hydrogen 37 °C (99 °F), which reflects the upper hydrogen content of titanium hydride. [ 16 ]
There are many types of heat treating processes available to titanium hydride. The most common are annealing and quenching. Annealing is the process of heating the titanium hydride to a sufficiently high temperature to soften it. This process occurs through three phases: recovery , recrystallization , and grain growth . The temperature required to anneal titanium hydride depends on the type of annealing. Annealing must be done under a hydrogen atmosphere to prevent outgassing . | https://en.wikipedia.org/wiki/Titanium_hydride |
Titanium nitride ( TiN ; sometimes known as tinite ) is an extremely hard ceramic material, often used as a physical vapor deposition (PVD) coating on titanium alloys , steel , carbide , and aluminium components to improve the substrate's surface properties.
Applied as a thin coating, TiN is used to harden and protect cutting and sliding surfaces, for decorative purposes (for its golden appearance), and as a non-toxic exterior for medical implants . In most applications a coating of less than 5 micrometres (0.00020 in) is applied. [ 5 ]
TiN has a Vickers hardness of 1800–2100, hardness of 31 ± 4 GPa , [ 6 ] a modulus of elasticity of 550 ± 50 GPa , [ 6 ] a thermal expansion coefficient of 9.35 × 10 −6 K −1 , and a superconducting transition temperature of 5.6 K. [ 7 ] [ 6 ]
TiN oxidizes at 800 °C in a normal atmosphere. It is chemically stable at 20 °C, according to laboratory tests, but can be slowly attacked by concentrated acid solutions with rising temperatures. [ 7 ] TiN has a brown color and appears gold when applied as a coating. Depending on the substrate material and surface finish, TiN has a coefficient of friction ranging from 0.4 to 0.9 against another TiN surface (non-lubricated). The typical TiN formation has a crystal structure of NaCl type with a roughly 1:1 stoichiometry ; TiN x compounds with x ranging from 0.6 to 1.2 are, however, thermodynamically stable. [ 8 ]
TiN becomes superconducting at cryogenic temperatures, with critical temperature up to 6.0 K for single crystals. [ 9 ] Superconductivity in thin-film TiN has been studied extensively, with the superconducting properties strongly varying depending on sample preparation, up to complete suppression of superconductivity at a superconductor–insulator transition . [ 10 ] A thin film of TiN was chilled to near absolute zero , converting it into the first known superinsulator , with resistance suddenly increasing by a factor of 100,000. [ 11 ]
Osbornite is a very rare natural form of titanium nitride, found almost exclusively in meteorites. [ 12 ] [ 13 ]
A well-known use for TiN coating is for edge retention and corrosion resistance on machine tooling, such as drill bits and milling cutters , often improving their lifetime by a factor of three or more. [ 14 ]
Because of the metallic gold color of TiN, this material is used to coat costume jewelry and automotive trim for decorative purposes. TiN is also widely used as a top-layer coating, usually with nickel - or chromium -plated substrates, on consumer plumbing fixtures and door hardware. As a coating, it is used in aerospace and military applications and to protect the sliding surfaces of suspension forks of bicycles and motorcycles , as well as the shock shafts of radio-controlled cars . TiN is also used as a protective coating on the moving parts of many rifles and semi-automatic firearms, as it is extremely durable. As well as being durable, it is also extremely smooth, making removing the carbon build-up extremely easy. TiN is non-toxic, meets FDA guidelines, [ 15 ] and has seen use in medical devices such as scalpel blades and orthopedic bone-saw blades, where sharpness and edge retention are important. [ 16 ] TiN coatings have also been used in implanted prostheses (especially hip replacement implants) and other medical implants.
Though less visible, thin films of TiN are also used in microelectronics , where they serve as a conductive connection between the active device and the metal contacts used to operate the circuit, while acting as a diffusion barrier to block the diffusion of the metal into the silicon. In this context, TiN is classified as a "barrier metal" (electrical resistivity ~ 25 μΩ·cm [ 2 ] ), even though it is clearly a ceramic from the perspective of chemistry or mechanical behavior. Recent chip design in the 45 nm technology and beyond also makes use of TiN as a "metal" for improved transistor performance. In combination with gate dielectrics (e.g. HfSiO 4 ) that have a higher permittivity compared to standard SiO 2 , the gate length can be scaled down with low leakage , higher drive current and the same or better threshold voltage . [ 17 ] Additionally, TiN thin films are currently under consideration for coating zirconium alloys for accident-tolerant nuclear fuels. [ 18 ] [ 19 ] It is also used as a coating on some compression driver diaphragms to improve performance.
Owing to their high biostability, TiN layers may also be used as electrodes in bioelectronic applications [ 20 ] like in intelligent implants or in-vivo biosensors that have to withstand the severe corrosion caused by body fluids . TiN electrodes have already been applied in the subretinal prosthesis project [ 21 ] as well as in biomedical microelectromechanical systems ( BioMEMS ). [ 22 ]
The most common methods of TiN thin film creation are physical vapor deposition (PVD, usually sputter deposition , cathodic arc deposition or electron-beam heating ) and chemical vapor deposition (CVD). [ 23 ] In both methods, pure titanium is sublimed and reacted with nitrogen in a high-energy, vacuum environment. TiN film may also be produced on Ti workpieces by reactive growth (for example, annealing ) in a nitrogen atmosphere. PVD is preferred for steel parts because the deposition temperatures exceeds the austenitizing temperature of steel. TiN layers are also sputtered on a variety of higher-melting-point materials such as stainless steels , titanium and titanium alloys . [ 24 ] Its high Young's modulus (values between 450 and 590 GPa have been reported in the literature [ 25 ] ) means that thick coatings tend to flake away, making them much less durable than thin ones. Titanium-nitride coatings can also be deposited by thermal spraying whereas TiN powders are produced by nitridation of titanium with nitrogen or ammonia at 1200 °C. [ 7 ]
Bulk ceramic objects can be fabricated by packing powdered metallic titanium into the desired shape, compressing it to the proper density, then igniting it in an atmosphere of pure nitrogen. The heat released by the chemical reaction between the metal and gas is sufficient to sinter the nitride reaction product into a hard, finished item. See powder metallurgy .
There are several commercially used variants of TiN that have been developed since 2010, such as titanium carbonitride (TiCN), titanium aluminium nitride (TiAlN or AlTiN), and titanium aluminum carbon nitride, which may be used individually or in alternating layers with TiN. These coatings offer similar or superior enhancements in corrosion resistance and hardness, and additional colors ranging from light gray to nearly black, to a dark, iridescent , bluish-purple, depending on the exact process of application. These coatings are becoming common on sporting goods, particularly knives and handguns , where they are used for both aesthetic and functional reasons.
Titanium nitride is also produced intentionally, within some steels, by judicious addition of titanium to the alloy . TiN forms at very high temperatures because of its very low enthalpy of formation , and even nucleates directly from the melt in secondary steel-making. It forms discrete, micrometre-sized cubic particles at grain boundaries and triple points, and prevents grain growth by Ostwald ripening up to very high homologous temperatures . Titanium nitride has the lowest solubility product of any metal nitride or carbide in austenite, a useful attribute in microalloyed steel formulas. | https://en.wikipedia.org/wiki/Titanium_nitride |
Titanium oxide may refer to: [ 2 ]
A common reduced titanium oxide is TiO, also known as titanium monoxide. It can be prepared from titanium dioxide and titanium metal at 1500 °C. [ 4 ]
Ti 3 O 5 , Ti 4 O 7 , and Ti 5 O 9 are non-stoichiometric oxides. These compounds are typically formed at high temperatures in the presence of excess oxygen. [ 5 ] [ 6 ] As a result, they exhibit unique structural and electronic properties, and have been studied for their potential use in various applications, including in gas sensors, lithium-ion batteries, and photocatalysis. [ 6 ] | https://en.wikipedia.org/wiki/Titanium_oxide |
Titanium powder metallurgy (P/M) offers the possibility of creating net shape or near net shape parts without the material loss and cost associated with having to machine intricate components from wrought billet. Powders can be produced by the blended elemental technique or by pre-alloying and then consolidated by metal injection moulding , hot isostatic pressing , direct powder rolling or laser engineered net shaping .
Titanium powder is used in aerospace , medical implants , 3D printing , powder metallurgy , and surface coatings due to its strength, low weight, and corrosion resistance. [ 1 ] It also plays a vital role in energy generation, sports equipment, and as a catalyst in chemical processes. [ 2 ]
The traditional technique of titanium production is via the Kroll process which involves chlorination of TiO 2 ore in the presence of carbon and reacting the resulting TiCl 4 with magnesium to produce titanium sponge. These processes take place at temperatures as high as 1040 °C. The sponge particle range in size from 45 to 180 μm, with particles ~150 μm termed 'sponge fines'. These fines are irregularly shaped and porous with a sponge-like morphology. [ 3 ] The fines are then blended with alloy additions; cold compacted into a green compact at up to 415 MPa then vacuum sintered at 1260 °C to produce a 99.5% dense component. Hot isostatic pressing (HIP) can further increase the density of these parts and produce components more economically than cast or wrought parts, but the porosity present in the material degrades fatigue and fracture properties. The BE approach has been used to produce valves for the Toyota Altezza, golf club heads and softball bats. [ 4 ] More recently, close to 100% dense Ti Grade 5 parts has been achieved using a hydrided powder along with 60:40 Al:V master alloy. The mechanical properties compare well with those exhibited by cast-and-wrought products. A cost estimate of less than $3.00 for a 0.320 g automotive connection link has been made.
Several techniques exist to produce pre-alloyed powder, such as Grade 5. In the hydride-dehydride process feedstock such as solid scrap, billet or machined turnings are processed to remove contaminants, hydrogenated to produce brittle material then ground under argon in a vibratory ball mill, typically at 400 °C for 4 hours at a pressure of 1 psi for Ti Grade 5. The resulting particles are angular and measure between 50 and 300 μm. Cold compaction after dehydrogenation of the powder, followed by either vacuum hot pressing (in this case the dehydrogenation process can be bypassed as hydrogen is removed under vacuum) or HIP and a final vacuum anneal, produces powders with hydrogen below 125 ppm. The possible presence of contaminants makes these powders unsuitable for use in critical aircraft applications.
In the plasma rotating electrode process (PREP), the feedstock, such as Ti Grade 5, is in the form of a rotating bar which is arced with gas plasma. The molten metal is centrifugally flung off the bar, cools down and is collected. The powders produced are spherical; between 100 and 300 μm is size, with good packing and flow characteristics, making the powder ideal for high quality, near net shapes produced by HIP, such as aviation parts and porous coatings on hip prostheses.
In the titanium gas atomisation (TGA) process, titanium is vacuum induction skull melted in a water cooled copper crucible, the metal tapped and the molten metal stream atomized with a stream of high pressure inert gas. The tiny droplets are spherical and measure between 50 and 350 μm. The TGA process has been used to produce a wide variety of materials such as commercially pure (CP) titanium, conventional alpha-beta and beta alloys. [ 5 ]
In plasma atomization (PA) process, a titanium wire is atomized by 3 inert gas plasma jets to form spherical metal powders. The distribution of diameter obtained in the PA process ranges between 0–200 μm and the powders obtained is very pure. The PA process specializes in the production of high temperature melting material as titanium (CP-Ti, Ti-6Al-4V), niobium , molybdenum, tantalum and many more. [ 5 ]
Several metal consolidation techniques are used to produce the final product. Metal injection moulding (MIM) otherwise known as powder injection moulding is a well-established and cost-effective method of fabricating small-to-moderate size metal components in large quantities. It is derived from the method plastic injection moulding, whereby mixing of a metal powder with a polymer binder forms the feedstock, which is then injected into a mould, after which the binder is removed via heat treatment under vacuum before final sintering. With titanium however, the binders used in MIM results in the introduction of carbon into the matrix due to insufficient binder removal prior to sintering and/or deleterious reactions between the decomposing binder, the debinding atmosphere, and the metal phase. This results in titanium parts with mechanical properties unsuited for critical aerospace applications, but suitable for parts where tensile and impact properties are less important. Recently, work has been carried out to reduce the binder to < 8% volume fraction, resulting in the complete removal of the binder from the moulded component during heat treatment.
In the direct powder rolling (DPR) process BE powder is used to produce sheet and plate and composite multilayered sheet and plates. Sheets between 1.27 and 2.54 mm and 50 to 99+% dense of single layer CP titanium, Ti Grade 5, TiAl (Ti-48Al-2Cr-2Nb) and composite Ti/Grade 5/Ti and Grade 5/TiAl/Grade 5 have been produced by DPR and sintering.
Laser engineered net shaping (LENS) is an additive manufacturing technique for rapidly fabricating, enhancing and repairing metal components directly from CAD data. The processes use a high power solid state laser focused onto a metal substrate to create a ~1 mm diameter melt pool. Metal powder is then injected into the melt pool to increase the material volume and build up the component layer by layer. Experimental gas thrusters (build time 8 hours) and automotive brackets have been manufactured in Ti-Grade 5. Selective Laser Sintering (SLS) is similar, except that the laser selectively fuses powdered material by scanning on the surface of a powder bed. After each cross-section is scanned, the powder bed is lowered by one layer thickness, a new layer of material is applied on top, and the process is repeated until the part is completed.
In hot isostatic pressing high temperature and pressure are used to consolidate powders to close to their maximum theoretical densities.
Electric current assisted sintering, also known as spark plasma sintering (SPS) relies on fast application of resistive heating and pressure to consolidate powders close to their maximum theoretical densities, without the undesired grain growth effect, thereby retaining close to original grain size and achieving improved mechanical properties in the final product.
Work is progressing on bypassing the conventional route of atomising wrought feedstock or sponge and the inherent cost associated with the traditional Kroll process. Several of these processes, such as the FFC, MER Corporation, OS, Ginatta and BHP Billiton processes rely on the electrolytic reduction of TiO 2 (a cheap and abundant material) to form Ti metal. So far, no material from these processes has been sold commercially on the open market, and cost models have yet to be published, but they offer the possibility of inexpensive titanium powder in the near future. The countries that have such facilities to generate Titanium Sponge are Saudi Arabia, China, Japan, Russia, Kazakhstan, the USA, Ukraine and India. The Titanium Sponge Plant in India is the only one in the world that can undertake all the different activities of manufacturing aerospace grade titanium sponge under one roof. [ 6 ] [ 7 ] | https://en.wikipedia.org/wiki/Titanium_powder |
Titanium tetrachloride is the inorganic compound with the formula TiCl 4 . It is an important intermediate in the production of titanium metal and the pigment titanium dioxide . TiCl 4 is a volatile liquid. Upon contact with humid air, it forms thick clouds of titanium dioxide ( TiO 2 ) and hydrochloric acid , a reaction that was formerly exploited for use in smoke machines. It is sometimes referred to as "tickle" or "tickle 4", as a phonetic representation of the symbols of its molecular formula ( TiCl 4 ). [ 7 ] [ 8 ]
TiCl 4 is a dense, colourless liquid, although crude samples may be yellow or even red-brown. It is one of the rare transition metal halides that is a liquid at room temperature, VCl 4 being another example. This property reflects the fact that molecules of TiCl 4 weakly self-associate. Most metal chlorides are polymers , wherein the chloride atoms bridge between the metals. Its melting point is similar to that of CCl 4 . [ 9 ] [ 10 ]
Ti 4+ has a "closed" electronic shell, with the same number of electrons as the noble gas argon . The tetrahedral structure for TiCl 4 is consistent with its description as a d 0 metal center ( Ti 4+ ) surrounded by four identical ligands. This configuration leads to highly symmetrical structures, hence the tetrahedral shape of the molecule. TiCl 4 adopts similar structures to TiBr 4 and TiI 4 ; the three compounds share many similarities. TiCl 4 and TiBr 4 react to give mixed halides TiCl 4− x Br x , where x = 0, 1, 2, 3, 4. Magnetic resonance measurements also indicate that halide exchange is also rapid between TiCl 4 and VCl 4 . [ 11 ]
TiCl 4 is soluble in toluene and chlorocarbons . Certain arenes form complexes of the type [(C 6 R 6 )TiCl 3 ] + . [ 12 ] TiCl 4 reacts exothermically with donor solvents such as THF to give hexacoordinated adducts . [ 13 ] Bulkier ligands (L) give pentacoordinated adducts TiCl 4 L .
TiCl 4 is produced by the chloride process , which involves the reduction of titanium oxide ores, typically ilmenite ( FeTiO 3 ), with carbon under flowing chlorine at 900 °C. Impurities are removed by distillation . [ 10 ]
The coproduction of FeCl 3 is undesirable, which has motivated the development of alternative technologies. Instead of directly using ilmenite, "rutile slag" is used. This material, an impure form of TiO 2 , is derived from ilmenite by removal of iron, either using carbon reduction or extraction with sulfuric acid . Crude TiCl 4 contains a variety of other volatile halides, including vanadyl chloride ( VOCl 3 ), silicon tetrachloride ( SiCl 4 ), and tin tetrachloride ( SnCl 4 ), which must be separated. [ 10 ]
The world's supply of titanium metal, about 250,000 tons per year, is made from TiCl 4 . The conversion involves the reduction of the tetrachloride with magnesium metal. This procedure is known as the Kroll process : [ 14 ]
In the Hunter process , liquid sodium is the reducing agent instead of magnesium. [ 15 ]
Around 90% of the TiCl 4 production is used to make the pigment titanium dioxide ( TiO 2 ). The conversion involves hydrolysis of TiCl 4 , a process that forms hydrogen chloride : [ 14 ]
In some cases, TiCl 4 is oxidised directly with oxygen :
It has been used to produce smoke screens since it produces a heavy, white smoke that has little tendency to rise. "Tickle" was the standard means of producing on-set smoke effects for motion pictures, before being phased out in the 1980s due to concerns about hydrated HCl 's effects on the respiratory system. [ citation needed ]
Titanium tetrachloride is a versatile reagent that forms diverse derivatives including those illustrated below. [ 16 ]
A characteristic reaction of TiCl 4 is its easy hydrolysis , signaled by the release of HCl vapors and titanium oxides and oxychlorides . Titanium tetrachloride has been used to create naval smokescreens , as the hydrochloric acid aerosol and titanium dioxide that is formed scatter light very efficiently. This smoke is corrosive, however. [ 10 ]
Alcohols react with TiCl 4 to give alkoxides with the formula [Ti(OR) 4 ] n (R = alkyl , n = 1, 2, 4). As indicated by their formula, these alkoxides can adopt complex structures ranging from monomers to tetramers. Such compounds are useful in materials science as well as organic synthesis . A well known derivative is titanium isopropoxide , which is a monomer. Titanium bis(acetylacetonate)dichloride results from treatment of titanium tetrachloride with excess acetylacetone : [ 17 ]
Organic amines react with TiCl 4 to give complexes containing amido ( R 2 N − -containing) and imido ( RN 2− -containing) complexes. With ammonia, titanium nitride is formed. An illustrative reaction is the synthesis of tetrakis(dimethylamido)titanium Ti(N(CH 3 ) 2 ) 4 , a yellow, benzene-soluble liquid: [ 18 ] This molecule is tetrahedral, with planar nitrogen centers. [ 19 ]
TiCl 4 is a Lewis acid as implicated by its tendency to hydrolyze . With the ether THF , TiCl 4 reacts to give yellow crystals of TiCl 4 (THF) 2 . With chloride salts, TiCl 4 reacts to form sequentially [Ti 2 Cl 9 ] − , [Ti 2 Cl 10 ] 2− (see figure above), and [TiCl 6 ] 2− . [ 20 ] The reaction of chloride ions with TiCl 4 depends on the counterion. [N(CH 2 CH 2 CH 2 CH 3 ) 4 ]Cl and TiCl 4 gives the pentacoordinate complex [N(CH 2 CH 2 CH 2 CH 3 ) 4 ][TiCl 5 ] , whereas smaller [N(CH 2 CH 3 ) 4 ] + gives [N(CH 2 CH 3 ) 4 ] 2 [Ti 2 Cl 10 ] . These reactions highlight the influence of electrostatics on the structures of compounds with highly ionic bonding.
Reduction of TiCl 4 with aluminium results in one-electron reduction. The trichloride ( TiCl 3 ) and tetrachloride have contrasting properties: the trichloride is a colored solid, being a coordination polymer , and is paramagnetic . When the reduction is conducted in THF solution, the Ti(III) product converts to the light-blue adduct TiCl 3 (THF) 3 .
The organometallic chemistry of titanium typically starts from TiCl 4 . An important reaction involves sodium cyclopentadienyl to give titanocene dichloride , TiCl 2 (C 5 H 5 ) 2 . This compound and many of its derivatives are precursors to Ziegler–Natta catalysts . Tebbe's reagent , useful in organic chemistry, is an aluminium-containing derivative of titanocene that arises from the reaction of titanocene dichloride with trimethylaluminium . It is used for the "olefination" reactions. [ 16 ]
Arenes , such as C 6 (CH 3 ) 6 react to give the piano-stool complexes [Ti(C 6 R 6 )Cl 3 ] + (R = H, CH 3 ; see figure above). This reaction illustrates the high Lewis acidity of the TiCl + 3 entity, which is generated by abstraction of chloride from TiCl 4 by AlCl 3 . [ 12 ]
TiCl 4 finds occasional use in organic synthesis , capitalizing on its Lewis acidity , its oxophilicity , and the electron-transfer properties of its reduced titanium halides. It is used in the Lewis acid catalysed aldol addition [ 21 ] Key to this application is the tendency of TiCl 4 to activate aldehydes (RCHO) by formation of adducts such as (RCHO)TiCl 4 OC(H)R . [ 22 ]
Hazards posed by titanium tetrachloride generally arise from its reaction with water that releases hydrochloric acid , which is severely corrosive itself and whose vapors are also extremely irritating. TiCl 4 is a strong Lewis acid , which exothermically forms adducts with even weak bases such as THF and water. | https://en.wikipedia.org/wiki/Titanium_tetrachloride |
Titer ( American English ) or titre ( British English ) is a way of expressing concentration . [ 1 ] Titer testing employs serial dilution to obtain approximate quantitative information from an analytical procedure that inherently only evaluates as positive or negative. The titer corresponds to the highest dilution factor that still yields a positive reading. [ 2 ] For example, positive readings in the first 8 serial, twofold dilutions translate into a titer of 1:256 (i.e., 2 −8 ). Titres are sometimes expressed by the denominator only, for example 1:256 is written 256. [ 3 ]
The term also has two other, conflicting meanings. In titration , the titer is the ratio of actual to nominal concentration of a titrant, e.g. a titer of 0.5 would require 1/0.5 = 2 times more titrant than nominal. This is to compensate for possible degradation of the titrant solution. Second, in textile engineering, titre is also a synonym for linear density .
Titer has the same origin as the word "title", from the French word titre , meaning "title" but referring to the documented purity of a substance, often gold or silver . This comes from the Latin word titulus , also meaning "title".
An antibody titer is a measurement of how much antibody an organism has produced that recognizes a particular epitope . It is conventionally expressed as the inverse of the greatest dilution level that still gives a positive result on some test. ELISA is a common means of determining antibody titers. For example, the indirect Coombs test detects the presence of anti-Rh antibodies in a pregnant woman's blood serum . A patient might be reported to have an "indirect Coombs titer" of 16. This means that the patient's serum gives a positive indirect Coombs test at any dilution down to 1/16 (1 part serum to 15 parts diluent). At greater dilutions the indirect Coombs test is negative. If a few weeks later the same patient had an indirect Coombs titer of 32 (1/32 dilution which is 1 part serum to 31 parts diluent), this would mean that she was making more anti-Rh antibody, since it took a greater dilution to abolish the positive test.
Many traditional serological tests such as hemagglutination or complement fixation employ this principle. Such tests can typically be read visually, which makes them fast, cost-effective, and able to be deployed in a wide variety of laboratory environments. The interpretation of any serological titer result is guided by reference values that are specific to the antigen or antibody in question, so a titer of 1:32 may be below the cut-off for one test but above for another.
A viral titer is the lowest concentration of a virus that still infects cells. To determine the titer, several dilutions are prepared, such as 10 −1 , 10 −2 , 10 −3 , ... 10 −8 . [ 1 ]
The titer of a fat is the temperature, in degrees Celsius, at which it solidifies. [ 4 ] The higher the titer, the harder the fat. This titer is used in determining whether an animal fat is considered tallow (titer higher than 40 °C) or a grease (titer below 40 °C). [ 5 ] | https://en.wikipedia.org/wiki/Titer |
Titermax is a mixture of compounds used in antibody generation and vaccination to stimulate the immune system to recognise an antigen given together with the mixture. Titermax is a developed immune adjuvant .
It is a water-in-oil emulsion and consists of squalene , an emulsifier (sorbitan monooleate 80), a patented block copolymer and microparticulate silica (Stills 2005). Toxicity seems to be lower than other water in oil adjuvant such as Freund's adjuvant . The efficacy to elicit an immune response against antigens of low immunogenicity is however subject to debate.
This antineoplastic or immunomodulatory drug article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Titermax |
In Vedic timekeeping , a tithi is a "duration of two faces of moon that is observed from earth", known as milа̄lyа̄ ( Newar : 𑐩𑐶𑐮𑐵𑐮𑑂𑐫𑐵𑑅, मिलाल्याः ) in Nepal Bhasa , [ 1 ] or the time it takes for the longitudinal angle between the Moon and the Sun to increase by 12 ° . In other words, a tithi is a time duration between the consecutive epochs that correspond to when the longitudinal angle between the Sun and the Moon is an integer multiple of 12°. Tithis begin at varying times of day and vary in duration approximately from 19 to 26 hours . [ 2 ] Every day of a lunar month is called tithi.
Traditional
A Hindu muhurta (forty-eight minute duration) can be represented in five attributes of Hindu astronomy namely, vara the weekday, tithi , nakshatra the Moon's asterism, yoga the angular relationship between Sun and Moon and karana half of tithi. [ 3 ]
Tithi plays an important role along with nakshatra in Hindus' daily as well as special activities in selecting the muhurta . There are auspicious tithis as well as inauspicious tithis , each considered more propitious for some purposes than for other. [ 4 ]
In amānta lunar calenders, tithi s are counted beginning at śukla pratipada , while in the pūrṇimānta lunar calenders, tithi s are counted from kr̥ṣṇa pratipada . The śukla tithi s are when the moon waxes, and the kr̥ṣṇa tithi s are when the moon wanes. The average tithi lasts 23 hours 37.5 minutes, and can range from 19 hours 59 minutes to 26 hours 47 minutes. The calculation of tithi timings may also differ on whether one uses the traditional methods for calculating the Sun and Moon's movement as promulgated in the Sūrya Siddhānta or modern methods which correctly calculate the true motions of the Sun and Moon. The tithi in place at sunrise is considered the " tithi of the day", although the tithi may end before the next sunrise in which case the next tithi begins. Because the length of a tithi is also variable a case can arise where a tithi begins after sunrise and ends prior to the next sunrise, which is called a kṣaya tithi . The opposite phenomenon can occur where a tithi in place during a sunrise is still present in the following sunrise which is called an adhika or ahorātra tithi . [ 5 ]
There are 30 tithis in each lunar month , named as: [ 6 ]
Tithi is one of the five elements of a Pañcāṅga . The other four elements:
This Hinduism-related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Tithi |
The Titius–Bode law (sometimes termed simply Bode's law ) is a formulaic prediction of spacing between planets in any given planetary system . The formula suggests that, extending outward, each planet should be approximately twice as far from the Sun as the one before. The hypothesis correctly anticipated the orbits of Ceres (in the asteroid belt ) and Uranus , but failed as a predictor of Neptune 's orbit. It is named after Johann Daniel Titius and Johann Elert Bode .
Later work by Mary Adela Blagg and D. E. Richardson significantly revised the original formula, and made predictions that were subsequently validated by new discoveries and observations. It is these re-formulations that offer "the best phenomenological representations of distances with which to investigate the theoretical significance of Titius–Bode type Laws". [ 1 ]
The law relates the semi-major axis a n {\displaystyle ~a_{n}~} of each planet's orbit outward from the Sun in units such that the Earth's semi-major axis is equal to 10:
a = 4 + x {\displaystyle ~a=4+x~}
where x = 0 , 3 , 6 , 12 , 24 , 48 , 96 , 192 , 384 , 768 … {\displaystyle ~x=0,3,6,12,24,48,96,192,384,768\ldots ~} such that, with the exception of the first step, each value is twice the previous value. There is another representation of the formula:
a = 4 + 3 × 2 n {\displaystyle ~a=4+3\times 2^{n}~}
where n = − ∞ , 0 , 1 , 2 , … . {\displaystyle ~n=-\infty ,0,1,2,\ldots ~.}
The resulting values can be divided by 10 to convert them into astronomical units ( AU ), resulting in the expression:
a = 0.4 + 0.3 × 2 n . {\displaystyle a=0.4+0.3\times 2^{n}~.}
For the far outer planets, beyond Saturn , each planet is predicted to be roughly twice as far from the Sun as the previous object. Whereas the Titius–Bode law predicts Saturn , Uranus , Neptune , and Pluto at about 10, 20, 39, and 77 AU , the actual values are closer to 10, 19, 30, 40 AU . [ a ]
The first mention of a series approximating Bode's law is found in a textbook by D. Gregory (1715): [ 2 ]
... supposing the distance of the Earth from the Sun to be divided into ten equal Parts, of these the distance of Mercury will be about four, of Venus seven, of Mars fifteen, of Jupiter fifty two, and that of Saturn ninety five. [ 3 ]
A similar sentence, likely paraphrased from Gregory (1715), [ 2 ] [ 3 ] appears in a work published by C. Wolff in 1724.
In 1764, C. Bonnet wrote: [ 4 ]
We know seventeen planets [that is, major planets and their satellites] that enter into the composition of our solar system; but we are not sure that there are no more. [ 4 ] [ 3 ]
In his 1766 translation of Bonnet's work, J. D. Titius added two of his own paragraphs to the statement above. The insertions were placed at the bottom of page 7 and at the top of page 8. The new paragraph is not in Bonnet's original French text, nor in translations of the work into Italian and English.
There are two parts to Titius's inserted text. The first part explains the succession of planetary distances from the Sun:
Take notice of the distances of the planets from one another, and recognize that almost all are separated from one another in a proportion which matches their bodily magnitudes. Divide the distance from the Sun to Saturn into 100 parts; then Mercury is separated by four such parts from the Sun, Venus by 4+3=7 such parts, the Earth by 4+6=10, Mars by 4+12=16. But notice that from Mars to Jupiter there comes a deviation from this so exact progression. From Mars there follows a space of 4+24=28 such parts, but so far no planet was sighted there. But should the Lord Architect have left that space empty? Not at all. Let us therefore assume that this space without doubt belongs to the still undiscovered satellites of Mars, let us also add that perhaps Jupiter still has around itself some smaller ones which have not been sighted yet by any telescope. Next to this for us still unexplored space there rises Jupiter's sphere of influence at 4+48=52 parts; and that of Saturn at 4+96=100 parts. [ citation needed ]
In 1772, J. E. Bode , then aged twenty-five, published an astronomical compendium, [ 5 ] in which he included the following footnote, citing Titius (in later editions): [ b ] [ 6 ]
This latter point seems in particular to follow from the astonishing relation which the known six planets observe in their distances from the Sun. Let the distance from the Sun to Saturn be taken as 100, then Mercury is separated by 4 such parts from the Sun. Venus is 4+3=7. The Earth 4+6=10. Mars 4+12=16. Now comes a gap in this so orderly progression. After Mars there follows a space of 4+24=28 parts, in which no planet has yet been seen. Can one believe that the Founder of the universe had left this space empty? Certainly not. From here we come to the distance of Jupiter by 4+48=52 parts, and finally to that of Saturn by 4+96=100 parts. [ 6 ]
These two statements, for all their peculiar expression, and from the radii used for the orbits, seem to stem from an antique algorithm by a cossist . [ c ]
Many precedents were found that predate the seventeenth century. [ citation needed ] Titius was a disciple of the German philosopher C. F. von Wolf (1679–1754), and the second part of the text that Titius inserted into Bonnet's work is in a book by von Wolf (1723), [ 7 ] suggesting that Titius learned the relation from him. Twentieth-century literature about Titius–Bode law attributes authorship to von Wolf. [ citation needed ] A prior version was written by D. Gregory (1702), [ 8 ] in which the succession of planetary distances 4, 7, 10, 16, 52, and 100 became a geometric progression with ratio 2. This is the nearest Newtonian formula, which was also cited by Benjamin Martin (1747) [ 9 ] and Tomàs Cerdà (c. 1760) [ 10 ] years before Titius's expanded translation of Bonnet's book into German (1766). Over the next two centuries, subsequent authors continued to present their own modified versions, apparently unaware of prior work. [ 1 ]
Titius and Bode hoped that the law would lead to the discovery of new planets, and indeed the discovery of Uranus and Ceres – both of whose distances fit well with the law – contributed to the law's fame. Neptune's distance was very discrepant, however, and indeed Pluto – no longer considered a planet – is at a mean distance that roughly corresponds to that the Titius–Bode law predicted for the next planet out from Uranus.
When originally published, the law was approximately satisfied by all the planets then known – i.e., Mercury through Saturn – with a gap between the fourth and fifth planets. Vikarius (Johann Friedrich) Wurm (1787) proposed a modified version of the Titius–Bode Law that accounted for the then-known satellites of Jupiter and Saturn, and better predicted the distance for Mercury. [ 11 ]
The Titius–Bode law was regarded as interesting, but of no great importance until the discovery of Uranus in 1781, which happens to fit into the series nearly exactly. Based on this discovery, Bode urged his contemporaries to search for a fifth planet. Ceres , the largest object in the asteroid belt , was found at Bode's predicted position in 1801.
Bode's law was widely accepted at that point, until in 1846 Neptune was discovered in a location that does not conform to the law. Simultaneously, due to the large number of asteroids discovered in the belt , Ceres was no longer considered a major planet. In 1898 the astronomer and logician C. S. Peirce used Bode's law as an example of fallacious reasoning. [ 12 ]
The discovery of Pluto in 1930 confounded the issue still further: Although nowhere near its predicted position according to Bode's law, it was very nearly at the position the law had designated for Neptune. The subsequent discovery of the Kuiper belt – and in particular the object Eris , which is more massive than Pluto, yet does not fit Bode's law – further discredited the formula. [ 13 ]
The Titius–Bode law predicts planets will be present at specific distances in astronomical units , which can be compared to the observed data for the planets and two dwarf planets in the Solar System:
In 1913, M. A. Blagg , an Oxford astronomer, revisited the law. [ 14 ] She analyzed the orbits of the planetary system and those of the satellite systems of the outer gas giants, Jupiter, Saturn and Uranus. She examined the log of the distances, trying to find the best 'average' difference.
Her analysis resulted in a different formula:
d i s t a n c e = A ⋅ [ B + f ( α + n β ) ] ( 1.7275 ) n . {\displaystyle \ {\mathsf {distance}}=A\cdot {\bigl [}\ B+f\left(\alpha +n\ \beta \right)\ {\bigr ]}\ {\bigl (}\ 1.7275\ {\bigr )}^{n}~.}
Note in particular that in Blagg's formula, the law for the Solar System was best represented by a progression in 1.7275 , rather than the original value 2 used by Titius, Bode, and others.
Blagg examined the satellite system of Jupiter , Saturn , and Uranus , and discovered the same progression ratio 1.7275 , in each.
However, the final form of the correction function f was not given in Blagg's 1913 paper, with Blagg noting that the empirical figures given were only for illustration. The empirical form was provided in the form of a graph (the reason that points on the curve are such a close match for empirical data, for objects discovered prior to 1913, is that they are the empirical data).
Finding a formula that closely fit the empircal curve turned out to be difficult. Fourier analysis of the shape resulted in the following seven term approximation: [ 14 ]
f ( θ ) = 0.4594 + 0.396 cos ( θ − 27.4 ∘ ) + 0.168 cos ( 2 ( θ − 60.4 ∘ ) ) + 0.062 cos ( 3 ( θ − 28.1 ∘ ) ) + + 0.053 cos ( 4 ( θ − 77.2 ∘ ) ) + 0.009 cos ( 5 ( θ − 22 ∘ ) ) + 0.012 cos ( 7 ( θ − 40.4 ∘ ) ) . {\displaystyle {\begin{aligned}\ f{\bigl (}\ \theta \ {\bigr )}\;=\;0.4594\;+\;\;&0.396\ \cos \!{\bigl (}\ \theta -27.4^{\circ }\ {\bigr )}\;+\;0.168\ \cos \!{\bigl (}\ 2\ (\ \theta -60.4^{\circ })\ {\bigr )}\;+\;0.062\ \cos \!{\bigl (}\ 3\ (\ \theta -28.1^{\circ })\ {\bigr )}\;+\;\\\;+\;\;&0.053\ \cos \!{\bigl (}\ 4\ (\ \theta -77.2^{\circ })\ {\bigr )}\;+\;0.009\ \cos \!{\bigl (}\ 5\ (\ \theta -22^{\circ })\ {\bigr )}\;+\;0.012\ \cos \!{\bigl (}\ 7\ (\ \theta -40.4^{\circ })\ {\bigr )}~.\end{aligned}}}
After further analysis, Blagg gave the following simpler formula; however the price for the simpler form is that it produces a less accurate fit to the empirical data. Blagg gave it in an un-normalized form in her paper, which leaves the relative sizes of A , B , and f ambiguous; it is shown here in normalized form (i.e. this version of f is scaled to produce values ranging from 0 to 1 , inclusive): [ 15 ]
f ( θ ) = 0.249 + 0.860 ( cos Ψ 3 − cos ( 2 Ψ ) + 1 6 − 4 cos ( 2 Ψ − 60 ∘ ) ) , {\displaystyle \ f{\bigl (}\ \theta \ {\bigr )}\;=\;0.249\;+\;0.860\ \left({\frac {\ \cos \ \Psi \ }{\ 3-\cos \!\left(\ 2\ \Psi \ \right)\ }}\;+\;{\frac {1}{\ 6-4\ \cos \!\left(\ 2\ \Psi -60^{\circ }\right)\ }}\right)\ ,}
where Ψ ≡ θ − 27.5 ∘ . {\displaystyle \ \Psi \equiv \theta -27.5^{\circ }~.}
Neither of these formulas for function f are used in the calculations below: The calculations here are based on a graph of function f which was drawn based on observed data.
Her paper was published in 1913, and was forgotten until 1953, when A. E. Roy came across it while researching another problem. [ 16 ] Roy noted that Blagg herself had suggested that her formula could give approximate mean distances of other bodies still undiscovered in 1913. Since then, six bodies in three systems examined by Blagg had been discovered: Pluto , Sinope ( Jupiter IX ), Lysithea ( J X ), Carme ( J XI ), Ananke ( J XII ), and Miranda ( Uranus V ).
Roy found that all six fitted very closely. This might have been an exaggeration: out of these six bodies, four were sharing positions with objects that were already known in 1913; concerning the two others, there was a ~6% overestimate for Pluto; and later, a 6% underestimate for Miranda became apparent. [ 15 ]
Bodies in parentheses were not known in 1913, when Blagg wrote her paper. Some of the calculated distances in the Saturn and Uranus systems are not very accurate. This is because the low values of constant B in the table above make them very sensitive to the exact form of the function f .
In a 1945 Popular Astronomy magazine article, [ 17 ] the science writer D. E. Richardson apparently independently arrived at the same conclusion as Blagg: That the progression ratio is 1.728 rather than 2 . His spacing law is in the form:
R n = ( 1.728 ) n ϱ n ( θ n ) , {\displaystyle \ R_{n}={\bigl (}\ 1.728\ {\bigr )}^{n}\ \varrho _{n}(\theta _{n})\ ,}
where ϱ n {\displaystyle \varrho _{n}} is an oscillatory function with period 2 π {\displaystyle 2\pi } , representing distances ϱ n {\displaystyle \varrho _{n}} from an off-centered origin to points on an ellipse.
Nieto, who conducted the first modern comprehensive review of the Titius–Bode Law, [ 18 ] noted that "The psychological hold of the Law on astronomy has been such that people have always tended to regard its original form as the one on which to base theories." He was emphatic that "future theories must rid themselves of the bias of trying to explain a progression ratio of 2":
One thing which needs to be emphasized is that the historical bias towards a progression ratio of 2 must be abandoned . It ought to be clear that the first formulation of Titius (with its asymmetric first term) should be viewed as a good first guess . Certainly, it should not necessarily be viewed as the best guess to refer theories to. But in astronomy the weight of history is heavy ... Despite the fact that the number 1.73 is much better, astronomers cling to the original number 2. [ 1 ]
No solid theoretical explanation underlies the Titius–Bode law – but it is possible that, given a combination of orbital resonance and shortage of degrees of freedom , any stable planetary system has a high probability of satisfying a Titius–Bode-type relationship. Since it may be a mathematical coincidence rather than a "law of nature", it is sometimes referred to as a rule instead of "law". [ 19 ] Astrophysicist Alan Boss states that it is just a coincidence, and the planetary science journal Icarus no longer accepts papers attempting to provide improved versions of the "law". [ 13 ]
Orbital resonance from major orbiting bodies creates regions around the Sun that are free of long-term stable orbits. Results from simulations of planetary formation support the idea that a randomly chosen, stable planetary system will likely satisfy a Titius–Bode law. [ 20 ]
Dubrulle and Graner [ 21 ] [ 22 ] showed that power-law distance rules can be a consequence of collapsing-cloud models of planetary systems possessing two symmetries: rotational invariance (i.e., the cloud and its contents are axially symmetric) and scale invariance (i.e., the cloud and its contents look the same on all scales). The latter is a feature of many phenomena considered to play a role in planetary formation, such as turbulence.
Only a limited number of systems are available upon which Bode's law can presently be tested; two solar planets have enough large moons that probably formed in a process similar to that which formed the planets: The four large satellites of Jupiter and the biggest inner satellite (i.e., Amalthea ) cling to a regular, but non-Titius-Bode, spacing, with the four innermost satellites locked into orbital periods that are each twice that of the next inner satellite. Similarly, the large moons of Uranus have a regular but non-Titius-Bode spacing. [ 23 ] However, according to Martin Harwit
a slight new phrasing of this law permits us to include not only planetary orbits around the Sun, but also the orbits of moons around their parent planets. [ 24 ]
The new phrasing is known as " Dermott's law ".
Of the recent discoveries of extrasolar planetary systems, few have enough known planets to test whether similar rules apply. An attempt with 55 Cancri suggested the equation
a n = 0.0142 ⋅ e ( 0.9975 n ) = 0.0142 ⋅ ( 2.7115 ) n , {\displaystyle ~a_{n}=0.0142\cdot \mathrm {e} ^{\left(\,0.9975\,n\,\right)}=0.0142\cdot {\bigl (}\,2.7115\,{\bigr )}^{n}~,}
and controversially [ 25 ] predicts an undiscovered planet or asteroid field for n = 5 {\displaystyle ~n=5~} at 2 AU . [ 26 ] Furthermore, the orbital period and semi-major axis of the innermost planet in the 55 Cancri system have been greatly revised (from 2.817 days to 0.737 days and from 0.038 AU to 0.016 AU, respectively) since the publication of these studies. [ 27 ]
Recent astronomical research suggests that planetary systems around some other stars may follow Titius-Bode-like laws. [ 28 ] [ 29 ] Bovaird & Lineweaver (2013) [ 30 ] applied a generalized Titius-Bode relation to 68 exoplanet systems that contain four or more planets. They showed that 96% of these exoplanet systems adhere to a generalized Titius-Bode relation to a similar or greater extent than the Solar System does. The locations of potentially undetected exoplanets are predicted in each system. [ 30 ]
Subsequent research detected 5 candidate planets from the 97 planets predicted for the 68 planetary systems. The study showed that the actual number of planets could be larger. The occurrence rates of Mars- and Mercury-sized planets are unknown, so many planets could be missed due to their small size. Other possible reasons that may account for apparent discrepancies include planets that do not transit the star or circumstances in which the predicted space is occupied by circumstellar disks . Despite these types of allowances, the number of planets found with Titius–Bode law predictions was lower than expected. [ 31 ]
In a 2018 paper, the idea of a hypothetical eighth planet around TRAPPIST-1 named "TRAPPIST‑1i", was proposed by using the Titius–Bode law. TRAPPIST‑1i had a prediction based exclusively on the Titius–Bode law with an orbital period of 27.53 ± 0.83 days . [ 32 ]
Finally, raw statistics from exoplanetary orbits strongly point to a general fulfillment of Titius-Bode-like laws (with exponential increase of semi-major axes as a function of planetary index) in all the exoplanetary systems; when making a blind histogram of orbital semi-major axes for all the known exoplanets for which this magnitude is known, [ 33 ] and comparing it with what should be expected if planets distribute according to Titius-Bode-like laws, a significant degree of agreement (i.e., 78%) [ 34 ] is obtained. | https://en.wikipedia.org/wiki/Titius–Bode_law |
Titration (also known as titrimetry [ 1 ] and volumetric analysis ) is a common laboratory method of quantitative chemical analysis to determine the concentration of an identified analyte (a substance to be analyzed). A reagent , termed the titrant or titrator , [ 2 ] is prepared as a standard solution of known concentration and volume . The titrant reacts with a solution of analyte (which may also be termed the titrand [ 3 ] ) to determine the analyte's concentration. The volume of titrant that reacted with the analyte is termed the titration volume .
The word "titration" descends from the French word titrer (1543), meaning the proportion of gold or silver in coins or in works of gold or silver; i.e., a measure of fineness or purity. Tiltre became titre , [ 4 ] which thus came to mean the "fineness of alloyed gold", [ 5 ] and then the "concentration of a substance in a given sample". [ 6 ] In 1828, the French chemist Joseph Louis Gay-Lussac first used titre as a verb ( titrer ), meaning "to determine the concentration of a substance in a given sample". [ 7 ]
Volumetric analysis originated in late 18th-century France. French chemist François-Antoine-Henri Descroizilles ( fr ) developed the first burette (which was similar to a graduated cylinder) in 1791. [ 8 ] [ 9 ] [ 10 ] Gay-Lussac developed an improved version of the burette that included a side arm, and invented the terms " pipette " and " burette " in an 1824 paper on the standardization of indigo solutions. [ 11 ] The first true burette was invented in 1845 by the French chemist Étienne-Ossian Henry (1798–1873). [ 12 ] [ 13 ] [ 14 ] [ 15 ] A major improvement of the method and popularization of volumetric analysis was due to Karl Friedrich Mohr , who redesigned the burette into a simple and convenient form, and who wrote the first textbook on the topic, Lehrbuch der chemisch-analytischen Titrirmethode ( Textbook of analytical chemistry titration methods ), published in 1855. [ 16 ] [ 17 ]
A typical titration begins with a beaker or Erlenmeyer flask containing a very precise amount of the analyte and a small amount of indicator (such as phenolphthalein ) placed underneath a calibrated burette or chemistry pipetting syringe containing the titrant. [ 18 ] Small volumes of the titrant are then added to the analyte and indicator until the indicator changes color in reaction to the titrant saturation threshold, representing arrival at the endpoint of the titration, meaning the amount of titrant balances the amount of analyte present, according to the reaction between the two. Depending on the endpoint desired, single drops or less than a single drop of the titrant can make the difference between a permanent and temporary change in the indicator.
Typical titrations require titrant and analyte to be in a liquid (solution) form. Though solids are usually dissolved into an aqueous solution, other solvents such as glacial acetic acid or ethanol are used for special purposes (as in petrochemistry , which specializes in petroleum.) [ 19 ] Concentrated analytes are often diluted to improve accuracy.
Many non-acid–base titrations require a constant pH during the reaction. Therefore, a buffer solution may be added to the titration chamber to maintain the pH. [ 20 ]
In instances where two reactants in a sample may react with the titrant and only one is the desired analyte, a separate masking solution may be added to the reaction chamber which eliminates the effect of the unwanted ion. [ 21 ]
Some reduction-oxidation ( redox ) reactions may require heating the sample solution and titrating while the solution is still hot to increase the reaction rate . For instance, the oxidation of some oxalate solutions requires heating to 60 °C (140 °F) to maintain a reasonable rate of reaction. [ 22 ]
A titration curve is a curve in the graph the x -coordinate of which represents the volume of titrant added since the beginning of the titration, and the y -coordinate of which represents the concentration of the analyte at the corresponding stage of the titration (in an acid–base titration, the y -coordinate usually represents the pH of the solution). [ 23 ]
In an acid – base titration, the titration curve represents the strength of the corresponding acid and base. For a strong acid and a strong base, the curve will be relatively smooth and very steep near the equivalence point. Because of this, a small change in titrant volume near the equivalence point results in a large pH change, and many indicators would be appropriate (for instance litmus , phenolphthalein or bromothymol blue ).
If one reagent is a weak acid or base and the other is a strong acid or base, the titration curve is irregular and the pH shifts less with small additions of titrant near the equivalence point . For example, the titration curve for the titration between oxalic acid (a weak acid) and sodium hydroxide (a strong base) is pictured. The equivalence point occurs between pH 8-10, indicating the solution is basic at the equivalence point and an indicator such as phenolphthalein would be appropriate. Titration curves corresponding to weak bases and strong acids are similarly behaved, with the solution being acidic at the equivalence point and indicators such as methyl orange and bromothymol blue being most appropriate.
Titrations between a weak acid and a weak base have titration curves which are very irregular. Because of this, no definite indicator may be appropriate, and a pH meter is often used to monitor the reaction. [ 24 ]
The type of function that can be used to describe the curve is termed a sigmoid function .
There are many types of titrations with different procedures and goals. The most common types of qualitative titration are acid–base titrations and redox titrations .
Acid–base titrations depend on the neutralization between an acid and a base when mixed in solution. In addition to the sample, an appropriate pH indicator is added to the titration chamber, representing the pH range of the equivalence point. The acid–base indicator indicates the endpoint of the titration by changing color. The endpoint and the equivalence point are not exactly the same because the equivalence point is determined by the stoichiometry of the reaction while the endpoint is just the color change from the indicator. Thus, a careful selection of the indicator will reduce the indicator error. For example, if the equivalence point is at a pH of 8.4, then the phenolphthalein indicator would be used instead of Alizarin Yellow because phenolphthalein would reduce the indicator error. Common indicators, their colors, and the pH range in which they change color are given in the table above. [ 25 ] When more precise results are required, or when the reagents are a weak acid and a weak base, a pH meter or a conductance meter are used.
For very strong bases, such as organolithium reagent , metal amides , and hydrides , water is generally not a suitable solvent and indicators whose pKa are in the range of aqueous pH changes are of little use. Instead, the titrant and indicator used are much weaker acids, and anhydrous solvents such as THF are used. [ 26 ] [ 27 ]
The approximate pH during titration can be approximated by three kinds of calculations. Before beginning of titration, the concentration of [ H + ] {\displaystyle {\ce {[H+]}}} is calculated in an aqueous solution of weak acid before adding any base. When the number of moles of bases added equals the number of moles of initial acid or so called equivalence point , one of hydrolysis and the pH is calculated in the same way that the conjugate bases of the acid titrated was calculated. Between starting and end points, [ H + ] {\displaystyle {\ce {[H+]}}} is obtained from the Henderson-Hasselbalch equation and titration mixture is considered as buffer. In Henderson-Hasselbalch equation the [acid] and [base] are said to be the molarities that would have been present even with dissociation or hydrolysis. In a buffer, [ H + ] {\displaystyle {\ce {[H+]}}} can be calculated exactly but the dissociation of HA , the hydrolysis of A − {\displaystyle {\ce {A-}}} and self-ionization of water must be taken into account. [ 28 ] Four independent equations must be used: [ 29 ]
In the equations, n A {\displaystyle n_{{\ce {A}}}} and n B {\displaystyle n_{{\ce {B}}}} are the moles of acid ( HA ) and salt ( XA where X is the cation), respectively, used in the buffer, and the volume of solution is V . The law of mass action is applied to the ionization of water and the dissociation of acid to derived the first and second equations. The mass balance is used in the third equation, where the sum of V [ HA ] {\displaystyle V[{\ce {HA}}]} and V [ A − ] {\displaystyle V[{\ce {A-}}]} must equal to the number of moles of dissolved acid and base, respectively. Charge balance is used in the fourth equation, where the left hand side represents the total charge of the cations and the right hand side represents the total charge of the anions: n B V {\displaystyle {\frac {n_{{\ce {B}}}}{V}}} is the molarity of the cation (e.g. sodium, if sodium salt of the acid or sodium hydroxide is used in making the buffer). [ 30 ]
Redox titrations are based on a reduction-oxidation reaction between an oxidizing agent and a reducing agent. A potentiometer or a redox indicator is usually used to determine the endpoint of the titration, as when one of the constituents is the oxidizing agent potassium dichromate . The color change of the solution from orange to green is not definite, therefore an indicator such as sodium diphenylamine is used. [ 31 ] Analysis of wines for sulfur dioxide requires iodine as an oxidizing agent. In this case, starch is used as an indicator; a blue starch-iodine complex is formed in the presence of excess iodine, signalling the endpoint. [ 32 ]
Some redox titrations do not require an indicator, due to the intense color of the constituents. For instance, in permanganometry a slight persisting pink color signals the endpoint of the titration because of the color of the excess oxidizing agent potassium permanganate . [ 33 ] In iodometry , at sufficiently large concentrations, the disappearance of the deep red-brown triiodide ion can itself be used as an endpoint, though at lower concentrations sensitivity is improved by adding starch indicator , which forms an intensely blue complex with triiodide.
Gas phase titrations are titrations done in the gas phase , specifically as methods for determining reactive species by reaction with an excess of some other gas , acting as the titrant. In one common gas phase titration, gaseous ozone is titrated with nitrogen oxide according to the reaction
After the reaction is complete, the remaining titrant and product are quantified (e.g., by Fourier transform spectroscopy ) (FT-IR); this is used to determine the amount of analyte in the original sample.
Gas phase titration has several advantages over simple spectrophotometry . First, the measurement does not depend on path length, because the same path length is used for the measurement of both the excess titrant and the product. Second, the measurement does not depend on a linear change in absorbance as a function of analyte concentration as defined by the Beer–Lambert law . Third, it is useful for samples containing species which interfere at wavelengths typically used for the analyte. [ 36 ]
Complexometric titrations rely on the formation of a complex between the analyte and the titrant. In general, they require specialized complexometric indicators that form weak complexes with the analyte. The most common example is the use of starch indicator to increase the sensitivity of iodometric titration, the dark blue complex of starch with iodine and iodide being more visible than iodine alone. Other complexometric indicators are Eriochrome Black T for the titration of calcium and magnesium ions, and the chelating agent EDTA used to titrate metal ions in solution. [ 37 ]
Zeta potential titrations are titrations in which the completion is monitored by the zeta potential , rather than by an indicator , in order to characterize heterogeneous systems, such as colloids . [ 38 ] One of the uses is to determine the iso-electric point when surface charge becomes zero, achieved by changing the pH or adding surfactant . Another use is to determine the optimum dose for flocculation or stabilization . [ 39 ]
An assay is a type of biological titration used to determine the concentration of a virus or bacterium . Serial dilutions are performed on a sample in a fixed ratio (such as 1:1, 1:2, 1:4, 1:8, etc.) until the last dilution does not give a positive test for the presence of the virus. The positive or negative value may be determined by inspecting the infected cells visually under a microscope or by an immunoenzymetric method such as enzyme-linked immunosorbent assay (ELISA). This value is known as the titer . [ 40 ]
Different methods to determine the endpoint include: [ 41 ]
Though the terms equivalence point and endpoint are often used interchangeably, they are different terms. Equivalence point is the theoretical completion of the reaction: the volume of added titrant at which the number of moles of titrant is equal to the number of moles of analyte, or some multiple thereof (as in polyprotic acids). Endpoint is what is actually measured, a physical change in the solution as determined by an indicator or an instrument mentioned above. [ 42 ]
There is a slight difference between the endpoint and the equivalence point of the titration. This error is referred to as an indicator error, and it is indeterminate. [ 43 ] [ self-published source? ]
Back titration is a titration done in reverse; instead of titrating the original sample, a known excess of standard reagent is added to the solution, and the excess is titrated. A back titration is useful if the endpoint of the reverse titration is easier to identify than the endpoint of the normal titration, as with precipitation reactions. Back titrations are also useful if the reaction between the analyte and the titrant is very slow, or when the analyte is in a non- soluble solid. [ 44 ]
The titration process creates solutions with compositions ranging from pure acid to pure base. Identifying the pH associated with any stage in the titration process is relatively simple for monoprotic acids and bases. The presence of more than one acid or base group complicates these computations. Graphical methods, [ 45 ] such as the equiligraph, [ 46 ] have long been used to account for the interaction of coupled equilibria. | https://en.wikipedia.org/wiki/Titration |
Titrations are often recorded on graphs called titration curves , which generally contain the volume of the titrant as the independent variable and the pH of the solution as the dependent variable (because it changes depending on the composition of the two solutions). [ 1 ]
The equivalence point on the graph is where all of the starting solution (usually an acid ) has been neutralized by the titrant (usually a base ). It can be calculated precisely by finding the second derivative of the titration curve and computing the points of inflection (where the graph changes concavity ); however, in most cases, simple visual inspection of the curve will suffice. In the curve given to the right, both equivalence points are visible, after roughly 15 and 30 mL of NaOH solution has been titrated into the oxalic acid solution. To calculate the logarithmic acid dissociation constant (pK a ), one must find the volume at the half-equivalence point, that is where half the amount of titrant has been added to form the next compound (here, sodium hydrogen oxalate, then disodium oxalate ). Halfway between each equivalence point, at 7.5 mL and 22.5 mL, the pH observed was about 1.5 and 4, giving the pK a .
In weak monoprotic acids , the point halfway between the beginning of the curve (before any titrant has been added) and the equivalence point is significant: at that point, the concentrations of the two species (the acid and conjugate base) are equal. Therefore, the Henderson-Hasselbalch equation can be solved in this manner:
Therefore, one can easily find the pK a of the weak monoprotic acid by finding the pH of the point halfway between the beginning of the curve and the equivalence point, and solving the simplified equation. In the case of the sample curve, the acid dissociation constant K a = 10 -pKa would be approximately 1.78×10 −5 from visual inspection (the actual K a2 is 1.7×10 −5 )
For polyprotic acids, calculating the acid dissociation constants is only marginally more difficult: the first acid dissociation constant can be calculated the same way as it would be calculated in a monoprotic acid. The pK a of the second acid dissociation constant, however, is the pH at the point halfway between the first equivalence point and the second equivalence point (and so on for acids that release more than two protons, such as phosphoric acid ). | https://en.wikipedia.org/wiki/Titration_curve |
In mathematics , the following inequality is known as Titu's lemma , Bergström's inequality , Engel's form or Sedrakyan's inequality , respectively, referring to the article About the applications of one useful inequality of Nairi Sedrakyan published in 1997, [ 1 ] to the book Problem-solving strategies of Arthur Engel published in 1998 and to the book Mathematical Olympiad Treasures of Titu Andreescu published in 2003. [ 2 ] [ 3 ] It is a direct consequence of Cauchy–Bunyakovsky–Schwarz inequality . Nevertheless, in his article (1997) Sedrakyan has noticed that written in this form this inequality can be used as a proof technique and it has very useful new applications. In the book Algebraic Inequalities (Sedrakyan) several generalizations of this inequality are provided. [ 4 ]
For any real numbers a 1 , a 2 , a 3 , … , a n {\displaystyle a_{1},a_{2},a_{3},\ldots ,a_{n}} and positive reals b 1 , b 2 , b 3 , … , b n , {\displaystyle b_{1},b_{2},b_{3},\ldots ,b_{n},} we have a 1 2 b 1 + a 2 2 b 2 + ⋯ + a n 2 b n ≥ ( a 1 + a 2 + ⋯ + a n ) 2 b 1 + b 2 + ⋯ + b n . {\displaystyle {\frac {a_{1}^{2}}{b_{1}}}+{\frac {a_{2}^{2}}{b_{2}}}+\cdots +{\frac {a_{n}^{2}}{b_{n}}}\geq {\frac {\left(a_{1}+a_{2}+\cdots +a_{n}\right)^{2}}{b_{1}+b_{2}+\cdots +b_{n}}}.} ( Nairi Sedrakyan (1997), Arthur Engel (1998), Titu Andreescu (2003))
Similarly to the Cauchy–Schwarz inequality , one can generalize Sedrakyan's inequality to random variables .
In this formulation let X {\displaystyle X} be a real random variable, and let Y {\displaystyle Y} be a positive random variable. X and Y need not be independent , but we assume E [ | X | ] {\displaystyle E[|X|]} and E [ Y ] {\displaystyle E[Y]} are both defined.
Then E [ X 2 / Y ] ≥ E [ | X | ] 2 / E [ Y ] ≥ E [ X ] 2 / E [ Y ] . {\displaystyle \operatorname {E} [X^{2}/Y]\geq \operatorname {E} [|X|]^{2}/\operatorname {E} [Y]\geq \operatorname {E} [X]^{2}/\operatorname {E} [Y].}
Example 1. Nesbitt's inequality .
For positive real numbers a , b , c : {\displaystyle a,b,c:} a b + c + b a + c + c a + b ≥ 3 2 . {\displaystyle {\frac {a}{b+c}}+{\frac {b}{a+c}}+{\frac {c}{a+b}}\geq {\frac {3}{2}}.}
Example 2. International Mathematical Olympiad (IMO) 1995.
For positive real numbers a , b , c {\displaystyle a,b,c} , where a b c = 1 {\displaystyle abc=1} we have that 1 a 3 ( b + c ) + 1 b 3 ( a + c ) + 1 c 3 ( a + b ) ≥ 3 2 . {\displaystyle {\frac {1}{a^{3}(b+c)}}+{\frac {1}{b^{3}(a+c)}}+{\frac {1}{c^{3}(a+b)}}\geq {\frac {3}{2}}.}
Example 3.
For positive real numbers a , b {\displaystyle a,b} we have that 8 ( a 4 + b 4 ) ≥ ( a + b ) 4 . {\displaystyle 8(a^{4}+b^{4})\geq (a+b)^{4}.}
Example 4.
For positive real numbers a , b , c {\displaystyle a,b,c} we have that 1 a + b + 1 b + c + 1 a + c ≥ 9 2 ( a + b + c ) . {\displaystyle {\frac {1}{a+b}}+{\frac {1}{b+c}}+{\frac {1}{a+c}}\geq {\frac {9}{2(a+b+c)}}.}
Example 1.
Proof : Use n = 3 , {\displaystyle n=3,} ( a 1 , a 2 , a 3 ) := ( a , b , c ) , {\displaystyle \left(a_{1},a_{2},a_{3}\right):=(a,b,c),} and ( b 1 , b 2 , b 3 ) := ( a ( b + c ) , b ( c + a ) , c ( a + b ) ) {\displaystyle \left(b_{1},b_{2},b_{3}\right):=(a(b+c),b(c+a),c(a+b))} to conclude: a 2 a ( b + c ) + b 2 b ( c + a ) + c 2 c ( a + b ) ≥ ( a + b + c ) 2 a ( b + c ) + b ( c + a ) + c ( a + b ) = a 2 + b 2 + c 2 + 2 ( a b + b c + c a ) 2 ( a b + b c + c a ) = a 2 + b 2 + c 2 2 ( a b + b c + c a ) + 1 ≥ 1 2 ( 1 ) + 1 = 3 2 . ◼ {\displaystyle {\frac {a^{2}}{a(b+c)}}+{\frac {b^{2}}{b(c+a)}}+{\frac {c^{2}}{c(a+b)}}\geq {\frac {(a+b+c)^{2}}{a(b+c)+b(c+a)+c(a+b)}}={\frac {a^{2}+b^{2}+c^{2}+2(ab+bc+ca)}{2(ab+bc+ca)}}={\frac {a^{2}+b^{2}+c^{2}}{2(ab+bc+ca)}}+1\geq {\frac {1}{2}}(1)+1={\frac {3}{2}}.\blacksquare }
Example 2.
We have that ( 1 a ) 2 a ( b + c ) + ( 1 b ) 2 b ( a + c ) + ( 1 c ) 2 c ( a + b ) ≥ ( 1 a + 1 b + 1 c ) 2 2 ( a b + b c + a c ) = a b + b c + a c 2 a 2 b 2 c 2 ≥ 3 a 2 b 2 c 2 3 2 a 2 b 2 c 2 = 3 2 . {\displaystyle {\frac {{\Big (}{\frac {1}{a}}{\Big )}^{2}}{a(b+c)}}+{\frac {{\Big (}{\frac {1}{b}}{\Big )}^{2}}{b(a+c)}}+{\frac {{\Big (}{\frac {1}{c}}{\Big )}^{2}}{c(a+b)}}\geq {\frac {{\Big (}{\frac {1}{a}}+{\frac {1}{b}}+{\frac {1}{c}}{\Big )}^{2}}{2(ab+bc+ac)}}={\frac {ab+bc+ac}{2a^{2}b^{2}c^{2}}}\geq {\frac {3{\sqrt[{3}]{a^{2}b^{2}c^{2}}}}{2a^{2}b^{2}c^{2}}}={\frac {3}{2}}.}
Example 3.
We have a 2 1 + b 2 1 ≥ ( a + b ) 2 2 {\displaystyle {\frac {a^{2}}{1}}+{\frac {b^{2}}{1}}\geq {\frac {(a+b)^{2}}{2}}} so that a 4 + b 4 = ( a 2 ) 2 1 + ( b 2 ) 2 1 ≥ ( a 2 + b 2 ) 2 2 ≥ ( ( a + b ) 2 2 ) 2 2 = ( a + b ) 4 8 . {\displaystyle a^{4}+b^{4}={\frac {\left(a^{2}\right)^{2}}{1}}+{\frac {\left(b^{2}\right)^{2}}{1}}\geq {\frac {\left(a^{2}+b^{2}\right)^{2}}{2}}\geq {\frac {\left({\frac {(a+b)^{2}}{2}}\right)^{2}}{2}}={\frac {(a+b)^{4}}{8}}.}
Example 4.
We have that 1 a + b + 1 b + c + 1 a + c ≥ ( 1 + 1 + 1 ) 2 2 ( a + b + c ) = 9 2 ( a + b + c ) . {\displaystyle {\frac {1}{a+b}}+{\frac {1}{b+c}}+{\frac {1}{a+c}}\geq {\frac {(1+1+1)^{2}}{2(a+b+c)}}={\frac {9}{2(a+b+c)}}.} | https://en.wikipedia.org/wiki/Titu's_lemma |
Tizen ( / ˈ t aɪ z ɛ n / ) is a Linux-based operating system primarily developed by Samsung Electronics and supported by the Linux Foundation .
The project was originally conceived as an HTML5 -based platform for mobile devices to succeed MeeGo . It was backed by other companies under the Tizen Association . Samsung merged its previous Linux-based OS effort, Bada , into Tizen and has since used it primarily on platforms such as wearable devices and smart TVs .
Much of Tizen is open source software , although the software development kit contains proprietary components owned by Samsung, and portions of the OS are licensed under the Flora License , a derivative of the Apache License 2.0 that grants a patent license only to "Tizen-certified platforms".
In May 2021, Google announced that Samsung would partner with the company on integrating Tizen features into Google's Android -derived Wear OS and committed to using it on future wearables, leaving Tizen to be mainly developed for Samsung Smart TVs. [ 3 ]
The project was initiated as mobile Linux and was launched by Intel in July 2007. In April 2009 the operating system updated to version 2.0 which was based on Fedora . However, in the same month, Intel turned Moblin over to the Linux Foundation for future development. Eventually, the operating system was merged with Nokia Maemo , a Debian based Linux distro, into MeeGo which was mainly developed by Nokia, Intel and Linux Foundation.
In 2011, after Nokia abandoned the project, Linux Foundation initiated the Tizen project as a successor to MeeGo, another Linux-based mobile operating system, with its main backer Intel joining Samsung Electronics , as well as Access Co. , NEC Casio , NTT DoCoMo , Panasonic Mobile , SK Telecom , Telefónica , and Vodafone as commercial partners. Tizen would be designed to use HTML5 apps, and target mobile and embedded platforms such as netbooks , smartphones, tablets, smart TVs , and in-car entertainment systems. [ 4 ] U.S. carrier Sprint Corporation (which was a backer of MeeGo) joined the Tizen Association in May 2012. [ 5 ] On September 16, 2012, Automotive Grade Linux announced its intent to use Tizen as the basis of its reference distribution. [ 6 ]
In January 2013, Samsung announced its intent to release multiple Tizen-based phones that year. In February 2013, Samsung merged its Bada operating system into Tizen. [ 7 ] [ 8 ]
In October 2013, the first Tizen tablet was shipped by Systena. The tablet was part of a development kit exclusive to Japan. [ 9 ] [ 10 ] [ 11 ]
In 2014, Samsung released the Gear 2 smartwatch that used a Tizen-based operating system as opposed to Android . [ 12 ]
On May 14, 2014, it was announced that Tizen would ship with Qt. [ 13 ] This project was abandoned in January 2017. [ 14 ]
On February 21, 2016, Samsung announced the Samsung Connect Auto, a connected car solution offering diagnostic, Wi-Fi , and other car-connected services. The device plugs directly into the OBD-II port underneath the steering wheel. [ 15 ]
On November 16, 2016, Samsung said they would be collaborating with Microsoft to bring .NET Core support to Tizen. [ 16 ]
According to Strategy Analytics research, approximately 21% of the smart TVs sold in 2018 run on the Tizen platform making it the most popular smart TV platform. [ 17 ]
On May 19, 2021, during Google I/O , Google announced that Samsung had agreed to work on integrating features of Tizen with the next version of Wear OS , and that it had committed to using Wear OS for its future wearable products. [ 18 ] [ 19 ] [ 20 ] Samsung will continue to use Tizen for its smart TVs. [ 21 ]
On December 31, 2021, the Tizen app store permanently closed. [ 22 ] The last smartphone based on the Tizen operating system is the Samsung Z4 which was released in 2017. The company switched to Google's Wear OS 3 platform on its Galaxy Watch 4 smartwatches. [ 23 ] [ 24 ]
Samsung Z was a series of low-cost smartphones for emerging markets. The first smartphone in the line was launched in 2015 and the last one in 2017.
Never released developer phones (codename Redwood)
There was also Samsung S III Tizen variant, codename RD-PQ, which was distributed to developers who created apps for Tizen [ 61 ]
On April 3, 2017, Vice reported on its "Motherboard" website that Amihai Neiderman, an Israeli security expert, has found more than 40 zero-day vulnerabilities in Tizen's code, allowing hackers to remotely access a wide variety of current Samsung products running Tizen, such as Smart TVs and mobile phones. [ 66 ] After the article was published, Samsung, whom Neiderman tried to contact months before, reached out to him to resolve the issues. [ 66 ]
In December 2016, Samsung created TizenRT, [ 67 ] a fork of NuttX , a real-time operating system (RTOS), for smart home appliances and IoT devices. | https://en.wikipedia.org/wiki/Tizen |
The Tizen Association , formerly the LiMo Foundation (short for Linux Mobile), is a non-profit consortium which develops and maintains the Tizen mobile operating system . Tizen is a Linux -based operating system for smartphones and other mobile devices. The founding members were Motorola , NEC , NTT DoCoMo , Panasonic Mobile Communications , Samsung Electronics , and Vodafone . The consortium's work resulted in the LiMo Platform —which was integrated into mobile phone products from NEC, Panasonic and Samsung—and later became the Tizen platform.
Members of the Tizen Association are:
Phones using LiMo include:
In the end of September 2011 it was announced by the Linux Foundation that MeeGo will be totally replaced by the Tizen mobile operating system project during 2012. Tizen will be a new free and open source Linux-based operating-system which itself will not be released until the first quarter of 2012. Intel and Samsung , in collaboration with the LiMo Foundation and assisting MeeGo developers, have been pointed out to lead the development of this new software platform, using third-party developer frameworks that will primarily be built on the HTML5 and other web standards . [ 13 ] [ 14 ] [ 15 ] [ 16 ] [ 17 ] [ 18 ] As of October 2012, the LiMo website traffic is redirected to tizen.org.
This article about a business, industry, or trade-related organization is a stub . You can help Wikipedia by expanding it .
This Linux -related article is a stub . You can help Wikipedia by expanding it .
This mobile technology related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Tizen_Association |
Thallium(I) carbonate is the inorganic compound with the formula Tl 2 CO 3 . It is a white, water-soluble salt. It has no or very few commercial applications. It is produced by treatment of thallous hydroxide with CO 2 . [ 3 ]
Like other thallium compounds, it is extremely toxic, with an oral median lethal dose of 21 mg/kg in mice. Due to its toxicity, it is listed in the United States List of Extremely Hazardous Substances as of 2007. [ 4 ]
This inorganic compound –related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Tl2CO3 |
Thallium(III) oxide , also known as thallic oxide , is a chemical compound of thallium and oxygen . It occurs in nature as the rare mineral avicennite . [ 4 ] Its structure is related to that of Mn 2 O 3 which has a bixbyite like structure. Tl 2 O 3 is metallic with high conductivity and is a degenerate n-type semiconductor which may have potential use in solar cells . [ 5 ] A method of producing Tl 2 O 3 by MOCVD is known. [ 6 ] Any practical use of thallium(III) oxide will always have to take account of thallium's poisonous nature. Contact with moisture and acids may form poisonous thallium compounds.
It is produced by the reaction of thallium with oxygen or hydrogen peroxide in an alkaline thallium(I) solution. Alternatively, it can be created by the oxidation of thallium(I) nitrate by chlorine in an aqueous potassium hydroxide solution. [ 7 ] | https://en.wikipedia.org/wiki/Tl2O3 |
Thallium(I) sulfate ( Tl 2 SO 4 ) or thallous sulfate is the sulfate salt of thallium in the common +1 oxidation state, as indicated by the Roman numeral I. It is often referred to as simply thallium sulfate. [ 2 ]
During the last two centuries, Tl 2 SO 4 had been used for various medical treatments but was abandoned. In the later 1900s it found use mainly for rodenticides . [ 3 ] These applications were prohibited in 1975 in the US due to the nonselective nature of its toxicity. Thallium(I) sulfate inhibits the growth of plants by preventing germination . Tl 2 SO 4 is mostly used today as a source of Tl + in the research laboratory. It is a precursor to thallium(I) sulfide (Tl 2 S), which exhibits high electrical conductivity when exposed to infrared light.
Thallium(I) sulfate is produced by the reaction of thallium metal with sulfuric acid followed by crystallization .
Tl 2 SO 4 adopts the same structure as K 2 SO 4 . In aqueous solution, the thallium(I) cations and the sulfate anions are separated and highly solvated . Thallium(I) sulfate crystals have a C 2 symmetry.
Thallium(I) sulfate is soluble in water and its toxic effects are derived from the thallium(I) cation. The mean lethal dose of thallium(I) sulfate for an adult is about 1 gram. Since thallium(I) sulfate is a simple powder with indistinctive properties, it can easily be mistaken for more innocuous chemicals. It can enter the body by ingestion, inhalation, or through contact with the skin. The thallium(I) cation is very similar to potassium and sodium cations, which are essential for life. After the thallium ion enters the cell, many of the processes that transport potassium and sodium are disrupted. Due to its poisonous nature, many western countries have banned the use of thallium(I) sulfate in products for home use and many companies have also stopped using this compound.
A dosage in excess of 500 mg is reported as fatal. Thallium(I) sulfate, after entering the body, concentrates itself in the kidneys, liver, brain, and other tissues in the body.
Thallium(I) sulfate was used in Israel to control the rodent population; it is suspected that in the 1950s, this resulted in the disappearance of the brown fish owl . [ 4 ] | https://en.wikipedia.org/wiki/Tl2SO4 |
Thallium(I) telluride (Tl 2 Te) is a chemical compound of thallium and tellurium . It has a structure related to that of Tl 5 Te 3 . [ 2 ] This compound is not well characterized. Its existence has only recently been confirmed by differential scanning calorimetry . [ 1 ] [ 3 ]
This inorganic compound –related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Tl2Te |
Thallium(I) bromide Thallium(I) iodide
Indium(III) fluoride Thallium(III) fluoride
Thallium(I) fluoride is the inorganic compound with the formula TlF. It is a white solid, forming orthorhombic crystals. The solid is slightly deliquescent . [ 1 ] It has a distorted sodium chloride ( rock salt ) crystal structure, [ 3 ] [ 4 ] due to the 6s 2 inert pair on Tl + . [ 5 ]
This salt is unusual among the thallium(I) halides in that it is very soluble in water. [ 6 ]
Thallium(I) fluoride can be prepared by the reaction of thallium(I) carbonate with hydrofluoric acid . [ 3 ] | https://en.wikipedia.org/wiki/TlF |
Thallium trifluoride is the inorganic compound with the formula TlF 3 . It is a white solid. Aside from being one of two thallium fluorides, the compound is only of theoretical interest. It adopts the same structure as bismuth trifluoride , featuring eight-coordinate Tl(III) centers. [ 1 ] Some evidence exists for a second polymorph. | https://en.wikipedia.org/wiki/TlF3 |
Thallium(I) iodide is a chemical compound with the formula Tl I . It is exists as both a solid and high temperature red polymorph . Thallium(I) iodide is one of several water-insoluble metal iodides , along with AgI , CuI , SnI 2 , SnI 4 , PbI 2 , and HgI 2 .
TlI can be formed in aqueous solution by metathesis of soluble thallium salt with iodide ion. [ 3 ] Alternatively, it has been prepared from the elements: [ 4 ]
An excess of iodine produces thallium(I) triiodide , Tl + I 3 − .
The room temperature form of TlI is yellow and has an orthorhombic structure [ 5 ] which can be considered to be a distorted NaCl structure. The distorted structure is may be caused by favorable thallium-thallium interactions, the closest Tl-Tl distance is 383 pm. [ 6 ] At 175 °C the yellow form transforms to a red CsCl form. This phase transition is accompanied by about two orders of magnitude jump in electrical conductivity. The CsI structure can be stabilized down to room temperature by doping TlI with other halides such as RbI, CsI, KI, AgI, TlBr and TlCl. [ 7 ] Thus, presence of impurities might be responsible for coexistence of the cubic and orthorhombic TlI phases at ambient conditions. [ 5 ] Under high pressure, 160 kbar, TlI becomes a metallic conductor. Nanometer-thin TlI films grown on LiF, NaCl or KBr substrates exhibit the cubic rocksalt structure. [ 8 ]
Thallium(I) iodide was initially added to mercury arc lamps to improve their performance [ 9 ] The light produced was mainly in the blue green part of the visible light spectrum least absorbed by water, so these have been used for underwater lighting. [ 10 ] In modern times, it is added to quartz and ceramic metal halide lamps that uses rare-earth halides like dysprosium , to increase their efficiency and to get the light color more close to the blackbody locus . Thallium iodide alone can be used to produces green colored metal halide lamps. Thallium(I) iodide is also used in trace amounts with NaI or CsI to produce scintillators used in radiation detectors.
Thallium(I) iodide is a rare mineral called nataliyamalikite. Small grains were found embedded in mascagnite sourced from fumaroles at Avachinsky , a volcano in Russia's Kamchatka Peninsula that can reach temperatures of 640 °C (1,184 °F). [ 11 ] [ 12 ]
Like all thallium compounds, thallium(I) iodide is highly toxic with an LD50 of 24.1mg/kg in rats . [ 13 ] | https://en.wikipedia.org/wiki/TlI |
Thallium triiodide , more precisely thallium(I) triiodide is a chemical compound of thallium and iodine with empirical formula TlI 3 . Unlike the other thallium trihalides , which contain thallium(III), TlI 3 is actually a thallium(I) salt containing thallium(I) cations Tl + and triiodide anions [I 3 ] − , and thus has the chemical formula Tl + [I 3 ] − . It is a black crystalline solid.
An appreciation as to why Tl + is not oxidised to Tl 3+ in the reaction:
can be gained by considering the standard reduction potentials of the half-cells which are:
The favoured reaction is therefore the reduction of Tl 3+ to Tl + (1.252 > 0.5355).
Using standard electrode potentials in this way must be done with caution as factors such as complex formation and solvation may affect the reaction. TlI 3 is no exception as it is possible to stabilise thallium(III) with excess I − forming the tetraiodothallate(III) ion [TlI 4 ] − ( isoelectronic with the tetraiodomercurate anion [HgI 4 ] 2− and with lead(IV) iodide PbI 4 ).
TlI 3 is formulated Tl + [I 3 ] − , and has a similar structure to NH 4 I 3 , CsI 3 and RbI 3 . [ 1 ] The triiodide ion in TlI 3 is nearly linear but is asymmetric with one iodine–iodine bond longer than the other. For comparison the dimensions of the triiodide, I a –I b –I c , ions in the different compounds are shown below:
TlI 3 can be prepared by the evaporation of stoichiometric quantities of thallium(I) iodide (TlI) and iodine in concentrated aqueous hydriodic acid , or by reacting TlI with iodine in ethanol . | https://en.wikipedia.org/wiki/TlI3 |
Thallium(I) nitrate , also known as thallous nitrate , is a thallium compound with the formula Tl NO 3 . It is a colorless and highly toxic salt.
Thallium(I) nitrate can be produced by reacting thallium(I) iodide with nitric acid . [ 1 ]
However, the production is simpler starting from the metal, its hydroxide or the carbonate : [ 2 ]
Thallium(I) nitrate is extremely toxic, like many other thallium compounds. It is highly toxic by ingestion but can also be absorbed through skin due to its solubility in water. [ 3 ] | https://en.wikipedia.org/wiki/TlNO3 |
Thallium has several oxides: | https://en.wikipedia.org/wiki/TlO2 |
Corrosive
Dangerous for the environment
Thallium(I) hydroxide , also called thallous hydroxide , is a chemical compound with the chemical formula Tl O H . It is a hydroxide of thallium , with thallium in oxidation state +1. It is a thallium(I) salt of water . It consists of thallium(I) cations Tl + and hydroxide anions OH − .
Thallium(I) hydroxide is obtained from the decomposition of thallium(I) ethoxide in water. [ 3 ]
This can also be done by direct reaction of thallium with ethanol and oxygen gas.
Another method is the reaction between thallium(I) sulfate and barium hydroxide .
Thallium(I) hydroxide is a strong base ; it dissociates to thallium (I) cations , Tl + , and hydroxide anions , OH − , except in strongly basic conditions . Tl + cation resembles an alkali metal cation, such as Li + , Na + or K + .
This inorganic compound –related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/TlOH |
Thulium(III) oxide is a pale green crystalline compound, with the formula Tm 2 O 3 . It was first isolated in 1879, from an impure sample of erbia , by Swedish chemist Per Teodor Cleve , who named it thulia .
Thulium(III) oxide has been made in the laboratory using various methods. One method involves burning thulium metal or its various salts in air. [ 3 ] [ 2 ]
Thulium(III) oxide can be made using a hydrothermal method where thulium(III) acetate is mixed with an ammonia solution, which causes thulium(III) oxide to precipitate as a white solid. [ 1 ]
Thulium(III) oxide (Tm₂O₃) is a pale green, thermally stable powder with a high melting point of 2,341 °C and a density of 8.6 g/cm³, typically forming a cubic crystal structure. [ 4 ] It is resistant to oxidation and dissolves in strong acids like hydrochloric acid , allowing it to form soluble thulium salts. [ 5 ] Due to its unique f-electron configuration, Tm₂O₃ has notable optical properties. [ 6 ] Thulium oxide (Tm₂O₃) is considered fibrogenic; it has the potential to induce tissue injury and fibrosis when inhaled or otherwise introduced to biological tissue. [ 7 ] | https://en.wikipedia.org/wiki/Tm2O3 |
Thulium(III) chloride or thulium trichloride is as an inorganic salt composed of thulium and chlorine with the formula TmCl 3 . It forms yellow crystals. Thulium(III) chloride has the YCl 3 ( AlCl 3 ) layer structure with octahedral thulium ions. [ 5 ] It has been used as a starting material for some exotic nanostructures prepared for NIR photocatalysis . [ 6 ] [ 7 ]
Thulium(III) chloride can be obtained by reacting thulium(III) oxide or thulium(III) carbonate and ammonium chloride : [ 8 ]
The hexahydrate of thulium(III) chloride can be obtained by adding thulium(III) oxide to concentrated hydrochloric acid . [ 1 ] [ 8 ]
Thulium(III) chloride can also be obtained by directly reacting thulium and chlorine: [ 9 ]
Thulium(III) chloride is a light yellow powder. Its hexahydrate is a light green hygroscopic solid. [ 6 ] Both are soluble in water. [ 10 ] Thulium(III) chloride has a monoclinic crystal structure with the space group C 2/m (No. 12) corresponding to that of aluminum(III) chloride. [ 10 ] [ 8 ]
Thulium(III) chloride reacts with strong bases to make thulium(III) oxide. | https://en.wikipedia.org/wiki/TmCl3 |
Thulium phosphide is an inorganic compound of thulium and phosphorus with the chemical formula TmP . [ 1 ] [ 2 ]
Reaction of thulium metal with phosphorus:
The dense phosphide film will prevent further reactions inside the metal. After etching gallium arsenide , an epitaxial layer of thulium phosphide can be grown on the surface to obtain a TmP/GaAs heterostructure. [ 3 ] [ 4 ]
The compound forms crystals of a cubic system , space group Fm 3 m . [ 5 ] TmP crystallizes in a NaCl -type structure at ambient pressure. [ 6 ]
The compound is a semiconductor used in high power, high frequency applications and in laser and other photo diodes . [ dubious – discuss ] [ 1 ] | https://en.wikipedia.org/wiki/TmP |
Tm is an abbreviation for anionic tridentate ligand based on three imidazole -2- thioketone groups bonded to a borohydride center. They are examples of scorpionate ligands . Various ligands in this family are known, differing in what substituents are on the imidazoles. The most common is Tm Me , which has a methyl group on the nitrogen. It is easily prepared by the reaction of molten methimazole (1-methylimidazole-2-thione) with sodium borohydride , giving the sodium salt of the ligand. Salts of the Tm Me anion are known also for lithium and potassium. Other alkyl - and aryl -group variations are likewise named Tm R according to those groups. [ 1 ]
The Tm Me anion is a tridentate, tripodal ligand topologically similar to the more common Tp ligands , but the two classes of ligands differ in several ways. Tm Me has three "soft" sulfur donor atoms, whereas Tp − has three nitrogen donor atoms. The thioamide sulfur is highly basic, as found for other thioureas . The Tm R anion simulates the environment provided by three facial thiolate ligands but without the 3- charge of a facial trithiolate. [ 2 ]
The large 8-membered SCNBNCSM chelate rings in M(Tm Me ) complexes are more flexible than the 6-membered CNBNCM rings in M(Tp) complexes. This flexibility enables the formation of boron - metal bonds, after loss of the B-H bond. This degradation of the coordinated Tm Me anion gives a dehydrogenated boranamide B(mt) 3 where mt = methimazolate. [ 3 ] | https://en.wikipedia.org/wiki/Tm_ligands |
ToFeT is a kinetic Monte Carlo electronic model of molecular films, able to simulate the time-of-flight experiment (ToF), field-effect transistors (FeTs). As its input, ToFeT takes a description of the film at a molecular level: a description of the position of all molecules and the interactions between them. As its output, ToFeT produces electrical characteristics such as mobilities , JV curves, and transient photocurrents . ToFeT thus allows the microscopic properties of a film to be related to its macroscopic electronic properties.
ToFeT is an open-source project, used by academic and industrial groups around the world. The current focus in ToFeT's development is to treat a wider range of materials systems, and reproduce a wider range of experimental measurements.
In Hebrew, the word "Tofet" stands for "inferno, scene of horror; hell", [ 1 ] thus providing a fitting indication to the complexity of the module.
This article about molecular modelling software is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/ToFeT |
The toadstone , also known as bufonite (from Latin bufo , "toad"), is a mythical stone or gem that was thought to be found in the head of a toad . It was supposed to be an antidote to poison and in this it is like batrachite , supposedly formed in the heads of frogs. Toadstones were actually the button-like fossilised teeth of Scheenstia (previously Lepidotes ), an extinct genus of ray-finned fish from the Jurassic and Cretaceous periods. They appeared to be "stones that are perfect in form" and were set by European jewellers into magical rings and amulets from Medieval times until the 18th century. [ 1 ]
From ancient times people associated the fossils with jewels that were set inside the heads of toads. The toad has poison glands in its skin, so it was naturally assumed that they carried their own antidote and that this took the form of a magical stone. They were first recorded by Pliny the Elder in the first century.
Like the fossilised shark teeth known as tonguestones , toadstones were thought to be antidotes for poison and were also used to treat epilepsy . [ 1 ] As early as the 14th century, people began to adorn jewelry with toadstones for their magical abilities. In their folklore, a toadstone was required to be removed from an old toad while the creature was still alive. 17th century naturalist Edward Topsell wrote that this could be done by setting the toad on a piece of red cloth. [ 1 ]
The true toadstone was taken by contemporary jewellers to be no bigger than the nail of a hand and they varied in colour from a whitish brown through green to black, depending on where they were buried. [ 2 ] They were supposedly most effective against poison when worn against the skin, on which occasion they were thought to heat up, sweat and change colour. [ 3 ] If a person were bitten by a venomous creature a toadstone would be touched against the affected part to effect a cure. [ 4 ] Alternatively Johannes de Cuba , in his book Gart der Gesundheit of 1485, claimed that toadstone would help with kidney disease and earthly happiness. [ 5 ]
Loose toadstones were discovered among other gemstones in the Elizabethan Cheapside Hoard and there are surviving toadstone rings in the Ashmolean Museum and the British Museum .
The toadstone is alluded to by Duke Senior in Shakespeare's As You Like It (1599), in Act 2, Scene 1, lines 12 to 14:
Sweet are the uses of adversity; Which, like the toad, ugly and venomous, Wears yet a precious jewel in his head.
In James Branch Cabell 's short story "Balthazar's Daughter" (collected in The Certain Hour ) and its subsequent play adaptation The Jewel Merchants , Alessandro de Medici attempts to seduce Graciosa by listing various precious jewels in his possession, including "jewels cut from the brain of a toad".
Some toadstones were used in jewelry, including on a crown held at Aachen Cathedral used to coronate Charles IV , Holy Roman Emperor. [ 6 ] | https://en.wikipedia.org/wiki/Toadstone |
Toast, Inc. is an American cloud-based restaurant management software company based in Boston , Massachusetts . The company provides an all-in-one point of sale (POS) system built on the Android operating system .
Toast's founders—Steve Fredette, Aman Narang, and Jonathan Grimm [ 1 ] —initially created a consumer app centered for mobile payments, customer loyalty, promotions, and social aspects that integrated with restaurants’ existing POS systems. [ 3 ]
In February 2020, Toast received $400 million in a round of Series F funding including Bessemer Venture Partners and TPG , at a valuation of $4.9 billion. [ 4 ] [ 5 ] As of June 2024 [update] , Toast is used in approximately 120,000 US restaurants. [ 6 ]
In April 2020, Toast laid off 50% of its workforce due to the COVID-19 pandemic and its economic impact on the restaurant industry. [ 7 ]
In November 2020, Toast had a secondary sale that valued the company at around $8 billion, despite laying off half of its employees in April. [ 8 ] On September 22, 2021, Toast went public with an initial public offering under the stock symbol TOST. [ 9 ] The company offered shares at $40 initially, with a market capitalization of roughly $20 billion, making it one of 2021's largest American IPOs. [ 10 ]
In February 2023, it was announced Toast had acquired the Costa Mesa -headquartered producer of digital display solutions and drive-thru technology for quick-service restaurants (QSRs), Delphi Display Systems. [ 11 ]
Toast headquarters were located at Landmark Center from 2015 until June 2023. [ 12 ]
First launched in March 2020, Toast's restaurant management system operates on the Android operating system and includes four devices: Flex (a terminal available in single-screen, guest-facing and kitchen displays), Tap (a three-in-one payment processing device that supports contactless payments), Toast Hub, and receipt printer . [ 13 ]
The company started supporting reservations in April 2023, entering into competition with OpenTable and Resy . [ 14 ]
In May 2016, the New England Venture Capital Association (NEVCA) named Toast the winner of the Hottest Startup: A+ at the 2016 NEVY awards. [ 15 ] [ 16 ] | https://en.wikipedia.org/wiki/Toast,_Inc. |
Toasternets were an early-1990s instantiation of the decentralized Internet , featuring open-standards -based federated services , radical decentralization , ad-hoc routing and consisting of many small individual and collective networks rather than a cartel of large commercial Internet Service Provider networks. Today's " community networks " and decentralized social networks are the closest modern inheritors of the ethos of the 1991-1994 era Toasternets. [ 2 ] [ 3 ]
The first known use of the word was by Robert Ullmann , then active in the Internet Engineering Task Force developing next-generation Internet addressing and routing protocols . He circulated the documents Toasternet Part I (December 1989) and Toasternet Part II (March 1992) on the IETF mailing list, then published RFCs 1475 and 1476 and the "CATNIP" Internet-Draft in June 1993. [ 4 ]
Early toasternet proponent Tim Pozar described a Toasternet as:
"an Internet-connected computer network built very cheaply so as to have a cost that a small business, school or individual can afford. It has been joking said that these networks are so cheap, you can connect everything in sight, including your toaster. Generally speaking, most Toasternets exist to meet a group's or individual's communications needs, rather than profit as a motive." [ 5 ]
Pozar, and other early toasternet builders Bill Woodcock and John Gilmore were participants in the cooperative The Little Garden, the first Internet service provider based on the west coast of the United States. Founded and led by Tom Jennings , The Little Garden (named for the Vietnamese restaurant where its foundational meetings were held) was an Internet Service Provider network built between 1992 and 1996 in the toasternet ethos, and consisting of constituent toasternet members; some individual, and some collective. Many of the initial Little Garden members went on to become founding members of Packet Clearing House , the not-for-profit which now supports core Internet infrastructure globally, but still continues to promulgate the toasternet values of collaborative competition and "permissionless" new market entry.
Writing contemporaneously in Wired , Jonathan Steuer said,
"Toasternets are not actually comprised of toasters and network cable. Rather, the term "toasternet" refers generically to small computer networks built out of cheap and readily available parts. Unlike commercial network service providers, who are motivated primarily by their bottom line, most toasternets exist to meet their members' communication needs -- to get people wired. Toasternets have become increasingly popular as demand for Internet services has outpaced the capabilities of commercial service providers." [ 6 ]
Gareth Bronwyn, also writing in Wired in 1993, defined them much more haphazardly, saying that they used "Cheap Internet routers made with old PCs" and coining the umbrella term "grunge computing." [ 7 ]
It is worthy of note that, prior to the 1992 privatization of the Internet via Al Gore 's National Information Infrastructure plan, the operation of toasternets was not actually legal , since Internet connectivity was supplied to authorized parties (generally defense contractors and research universities ) by, and at the expense of, the US Defense Department's Advanced Research Projects Agency , and toasternets extended access to the network beyond the parties authorized to use it.
Many people also linked the name with a much more literal demonstration of SNMP-enabled toasters which had been connected to an Ethernet network by network management software vendor Epilogue, which caught the public's fancy at the time, and received some press coverage. [ 8 ] | https://en.wikipedia.org/wiki/Toasternet |
Tobacco-specific nitrosamines ( TSNAs ) comprise one of the most important groups of carcinogens in tobacco products, particularly cigarettes (traditional and electronic ) and fermented dipping snuff.
These nitrosamine carcinogens are formed from nicotine and related compounds by a nitrosation reaction that occurs during the curing and processing of tobacco. [ 1 ] Essentially the plant's natural alkaloids combine with nitrate forming the nitrosamines. [ 2 ]
They are called tobacco-specific nitrosamines because they are found only in tobacco products, and possibly in some other nicotine-containing products. The tobacco-specific nitrosamines are present in cigarette smoke and to a lesser degree in "smokeless" tobacco products such as dipping tobacco and chewing tobacco ; additional information has shown that trace amounts of NNN and NNK have been detected in e-cigarettes. [ 3 ] They are present in trace amounts in snus . They are important carcinogens in cigarette smoke, along with combustion products and other carcinogens. [ 1 ]
Among the tobacco-specific nitrosamines, nicotine-derived nitrosamine ketone (NNK) and N -nitrosonornicotine (NNN) are the most carcinogenic. [ 1 ] Others include N ′ -nitrosoanatabine (NAT) and N -nitrosoanabasine (NAB). NNK and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are potent systemic lung carcinogens in rats. Tumors of the nasal cavity, liver, and pancreas are also observed in NNK- or NNAL-treated rats. NNN is an effective esophageal carcinogen in the rat, [ 4 ] and induces respiratory tract tumors in mice, hamsters, and mink. A mixture of NNK and NNN caused oral tumors when swabbed in the rat oral cavity. Thus, considerable evidence supports the role of tobacco-specific nitrosamines as important causative factors for cancers of the lung , pancreas , esophagus , and oral cavity in people who use tobacco products. [ 1 ]
Metabolism and chemical binding to DNA ( adduct formation) are critical in cancer induction by NNK and NNN.
Human metabolism of NNK and NNN varies widely from individual to individual, and current research is attempting to identify those individuals who are particularly sensitive to the carcinogenic effects of these compounds. Such individuals would be at higher risk for cancer when they use tobacco products or are exposed to secondhand smoke. Identification of high-risk individuals could lead to improved methods of prevention of tobacco-related cancer, and improved risk valuation for insurers. | https://en.wikipedia.org/wiki/Tobacco-specific_nitrosamines |
Tobacco mosaic virus [ a ] ( TMV ) is a positive-sense single-stranded RNA virus species in the genus Tobamovirus that infects a wide range of plants, especially tobacco and other members of the family Solanaceae . The infection causes characteristic patterns, such as " mosaic "-like mottling and discoloration on the leaves (hence the name). TMV was the first virus to be discovered. Although it was known from the late 19th century that a non-bacterial infectious disease was damaging tobacco crops, it was not until 1930 that the infectious agent was determined to be a virus. It is the first pathogen identified as a virus. The virus was crystallised by Wendell Meredith Stanley . It has a similar size to the largest synthetic molecule, known as PG5 with comparable length and diameter. [ 2 ] [ 3 ]
In 1886, Adolf Mayer first described the tobacco mosaic disease that could be transferred between plants, similar to bacterial infections. [ 4 ] [ 5 ] In 1892, Dmitri Ivanovsky gave the first concrete evidence for the existence of a non-bacterial infectious agent, showing that infected sap remained infectious even after filtering through the finest Chamberland filters . [ 5 ] [ 6 ] Later, in 1903, Ivanovsky published a paper describing abnormal crystal intracellular inclusions in the host cells of the affected tobacco plants and argued the connection between these inclusions and the infectious agent. [ 7 ] However, Ivanovsky remained rather convinced, despite repeated failures to produce evidence, that the causal agent was an unculturable bacterium, too small to be retained on the employed Chamberland filters and to be detected in the light microscope. In 1898, Martinus Beijerinck independently replicated Ivanovsky's filtration experiments and then showed that the infectious agent was able to reproduce and multiply in the host cells of the tobacco plant. [ 5 ] [ 8 ] Beijerinck adopted the term of " virus " to indicate that the causal agent of tobacco mosaic disease was of non-bacterial nature. Tobacco mosaic virus was the first virus to be crystallized. It exhibits liquid crystal phases above a critical density. [ 9 ] It was achieved by Wendell Meredith Stanley in 1935 who also showed that TMV remains active even after crystallization. [ 5 ] For his work, he was awarded 1/4 of the Nobel Prize in Chemistry in 1946, [ 10 ] [ 11 ] even though it was later shown some of his conclusions (in particular, that the crystals were pure protein, and assembled by autocatalysis ) were incorrect. [ 12 ] The first electron microscopical images of TMV were made in 1939 by Gustav Kausche , Edgar Pfankuch and Helmut Ruska – the brother of Nobel Prize winner Ernst Ruska . [ 13 ] In 1955, Heinz Fraenkel-Conrat and Robley Williams showed that purified TMV RNA and its capsid (coat) protein assemble by themselves to functional viruses, indicating that this is the most stable structure (the one with the lowest free energy).
The crystallographer Rosalind Franklin worked for Stanley for about a month at Berkeley , and later designed and built a model of TMV for the 1958 World's Fair at Brussels . In 1958, she speculated that the virus was hollow, not solid, and hypothesized that the RNA of TMV is single-stranded. [ 14 ] This conjecture was proven to be correct after her death and is now known to be the + strand. [ 15 ] The investigations of tobacco mosaic disease and subsequent discovery of its viral nature were instrumental in the establishment of the general concepts of virology . [ 5 ]
Tobacco mosaic virus has a rod-like appearance. Its capsid is made from 2130 molecules of coat protein and one molecule of genomic single strand RNA, 6400 bases long. The coat protein self-assembles into the rod-like helical structure (16.3 proteins per helix turn) around the RNA, which forms a hairpin loop structure (see the electron micrograph above). The structural organization of the virus gives stability. [ 16 ] The protein monomer consists of 158 amino acids which are assembled into four main alpha-helices, which are joined by a prominent loop proximal to the axis of the virion. Virions are ~300 nm in length and ~18 nm in diameter. [ 17 ] Negatively stained electron microphotographs show a distinct inner channel of radius ~2 nm. The RNA is located at a radius of ~4 nm and is protected from the action of cellular enzymes by the coat protein. [ 18 ] X-ray fiber diffraction structure of the intact virus was studied based on an electron density map at 3.6 Å resolution. [ 19 ] Inside the capsid helix, near the core, is the coiled RNA molecule, which is made up of 6,395 ±10 nucleotides. [ 20 ] [ 21 ] The structure of the virus plays an important role in the recognition of the viral DNA. This happens due to the formation of an obligatory intermediate produced from a protein allows the virus to recognize a specific RNA hairpin structure. [ 22 ] The intermediate induces the nucleation of TMV self-assembly by binding with the hairpin structure. [ 23 ]
The TMV genome consists of a 6.3–6.5 kbp single-stranded (ss) RNA . The 3’-terminus has a tRNA -like structure, and the 5’-terminus has a methylated nucleotide cap. (m7G5’pppG). [ 24 ] The genome encodes 4 open reading frames (ORFs), two of which produce a single protein due to ribosomal readthrough of a leaky UAG stop codon . The 4 genes encode a replicase (with methyltransferase [MT] and RNA helicase [Hel] domains), an RNA-dependent RNA polymerase , a so-called movement protein (MP) and a capsid protein (CP). [ 25 ] The coding sequence starts with the first reading frame, which is 69 nucleotides away from the 5' end of the RNA. [ 26 ] The noncoding region at the 5' end can be varied in different individual virions, but there hasn't been any variation found between virions in the noncoding region at the 3' end. [ 26 ]
TMV is a thermostable virus. On a dried leaf, it can withstand up to 50 °C (120 degree Fahrenheit) for 30 minutes. [ 27 ]
TMV has an index of refraction of about 1.57. [ 28 ]
TMV does not have a distinct overwintering structure. Rather, it will over-winter in infected tobacco stalks and leaves in the soil, on the surface of contaminated seed (TMV can even survive in contaminated tobacco products for many years, so smokers can accidentally transmit it by touch, although not in the smoke itself). [ 29 ] [ 30 ] With the direct contact with host plants through its vectors (normally insects such as aphids and leafhoppers ), TMV will go through the infection process and then the replication process.
After its multiplication, it enters the neighboring cells through plasmodesmata . The infection does not spread through contact with insects, [ 31 ] but instead spreads by direct contact to the neighboring cells . For its smooth entry, TMV produces a 30 k Da movement protein called P30 which enlarges the plasmodesmata. TMV most likely moves from cell-to-cell as a complex of the RNA, P30, and replicate proteins.
It can also spread through phloem for longer distance movement within the plant. Moreover, TMV can be transmitted from one plant to another by direct contact. Although TMV does not have defined transmission vectors, the virus can be easily transmitted from the infected hosts to the healthy plants by human handling.
Following entry into its host via mechanical inoculation, TMV uncoats itself to release its viral [+]RNA strand. As uncoating occurs, the MetHel:Pol gene is translated to make the capping enzyme MetHel and the RNA Polymerase. Then the viral genome will further replicate to produce multiple mRNAs via a [-]RNA intermediate primed by the tRNA HIS at the [+]RNA 3' end. The resulting mRNAs encode several proteins, including the coat protein and an RNA-dependent RNA polymerase (RdRp), as well as the movement protein. Thus TMV can replicate its own genome.
After the coat protein and RNA genome of TMV have been synthesized, they spontaneously assemble into complete TMV virions in a highly organized process. The protomers come together to form disks or 'lockwashers' composed of two layers of protomers arranged in a helix. The helical capsid grows by the addition of protomers to the end of the rod. As the rod lengthens, the RNA passes through a channel in its center and forms a loop at the growing end. In this way the RNA can easily fit as a spiral into the interior of the helical capsid. [ 32 ]
Like other plant pathogenic viruses, TMV has a very wide host range and has different effects depending on the host being infected. Tobacco mosaic virus has been known to cause a production loss for flue cured tobacco of up to two percent in North Carolina . [ 33 ] It is known to infect members of nine plant families, and at least 125 individual species, including tobacco, tomato , pepper (all members of the Solanaceae ), cucumbers , a number of ornamental flowers , [ 34 ] and beans including Phaseolus vulgaris and Vigna unguiculata . [ 35 ] There are many different strains. The first symptom of this virus disease is a light green coloration between the veins of young leaves . This is followed quickly by the development of a "mosaic" or mottled pattern of light and dark green areas in the leaves. Rugosity may also be seen where the infected plant leaves display small localized random wrinkles. These symptoms develop quickly and are more pronounced on younger leaves. Its infection does not result in plant death, but if infection occurs early in the season, plants are stunted. Lower leaves are subjected to "mosaic burn" especially during periods of hot and dry weather. In these cases, large dead areas develop in the leaves. This constitutes one of the most destructive phases of Tobacco mosaic virus infection. Infected leaves may be crinkled, puckered, or elongated. However, if TMV infects crops like grape and apple , it is almost symptomless. TMV is able to infect and complete its replication cycle in a plant pathogenic fungus, TMV is able to enter and replicate in cells of the fungi species Colletotrichum acutatum , C. clavatum, and C. theobromicola, which may not be an exception, although it has neither been found nor probably searched for in nature. [ 36 ]
TMV is one of the most stable viruses and has a wide survival range. As long as the surrounding temperature remains below approximately 40 degrees Celsius , TMV can sustain its stable form. All it needs is a host to infect. If necessary, greenhouses and botanical gardens would provide the most favorable condition for TMV to spread out, due to the high population density of possible hosts and the constant temperature throughout the year. It also could be useful to culture TMV in vitro in sap because it can survive up to 3000 days. [ 37 ]
One of the common control methods for TMV is sanitation , which includes removing infected plants and washing hands in between each planting. Crop rotation should also be employed to avoid infected soil/ seed beds for at least two years. As for any plant disease, looking for resistant strains against TMV may also be advised. Furthermore, the cross protection method can be administered, where the stronger strain of TMV infection is inhibited by infecting the host plant with a mild strain of TMV, similar to the effect of a vaccine .
In the past ten years, the application of genetic engineering on a host plant genome has been developed to allow the host plant to produce the TMV coat protein within their cells. It was hypothesized that the TMV genome will be re-coated rapidly upon entering the host cell, thus it prevents the initiation of TMV replication. Later it was found that the mechanism that protects the host from viral genome insertion is through gene silencing . [ 38 ]
TMV is inhibited by a product of the myxomycete slime mold Physarum polycephalum . Both tobacco and the beans P. vulgaris and V. sinensis suffered almost no lesioning in vitro from TMV when treated with a P. polycephalum extract. [ 35 ]
Research has shown that Bacillus spp . can be used to reduce the severity of symptoms from TMV in tobacco plants. In the study, treated tobacco plants had more growth and less build-up of TMV virions than tobacco plants that hadn't been treated. [ 39 ]
A research has been conducted by H.Fraenkel-Conrat to show the influence of acetic acid on the Tobacco Mosaic Virus. According to the research, 67% acetic acid resulted as degradation of the virus. [ 40 ]
Another possible source of prevention for TMV is the use of salicylic acid. A study completed by a research team at the University of Cambridge found that treating plants with salicylic acid reduced the amount of TMV viral RNAs and viral coat protein present in the tobacco plants. Their research showed that salicylic acid most likely was disrupting replication and transcription and more specifically, the RdRp complex. [ 41 ]
A research was conducted and revealed that humans have antibodies against Tobacco Mosaic Virus. [ 42 ]
The large amount of literature about TMV and its choice for many pioneering investigations in structural biology (including X-ray diffraction and X-ray crystallography ), virus assembly and disassembly, and so on, are fundamentally due to the large quantities that can be obtained, plus the fact that it does not infect animals. After growing several hundred infected tobacco plants in a greenhouse , followed by a few simple laboratory procedures, a scientist can produce several grams of the virus. [ 43 ] In fact, tobacco mosaic virus is so proliferate that the inclusion bodies can be seen with only a light microscope. [ 31 ]
James D. Watson , in his memoir The Double Helix , cites his x-ray investigation of TMV's helical structure as an important step in deducing the nature of the DNA molecule. [ 44 ]
Plant viruses can be used to engineer viral vectors , tools commonly used by molecular biologists to deliver genetic material into plant cells ; they are also sources of biomaterials and nanotechnology devices. [ 45 ] [ 46 ] Viral vectors based on TMV include those of the magnICON and TRBO plant expression technologies. [ 46 ] [ 47 ] Due to its cylindrical shape, high aspect ratio, self-assembling nature, and ability to incorporate metal coatings ( nickel and cobalt ) into its shell, TMV is an ideal candidate to be incorporated into battery electrodes . [ 48 ] Addition of TMV to a battery electrode increases the reactive surface area by an order of magnitude, resulting in an increase in the battery's capacity by up to six times compared to a planar electrode geometry. [ 48 ] [ 49 ] The TMV-based vector also enabled C. acutatum to transiently express exogenous GFP up to six subcultures and for at least 2 mo after infection, without the need to develop transformation technology, RNAi can be expressed in the phytopathogenic fungus Colletotrichum acutatum by VIGS using a recombinant vector based on TMV in which the ORF of the gene encoding the green fluorescent protein (GFP) was transcribed in fungal cells from a duplicate of the TMV coat protein (CP) subgenomic mRNA promoter and demonstrated that the approach could be used to obtain foreign protein expression in fungi. [ 36 ] | https://en.wikipedia.org/wiki/Tobacco_mosaic_virus |
Tobacco package warning messages are warning messages that appear on the packaging of cigarettes and other tobacco products concerning their health effects . They have been implemented in an effort to enhance the public's awareness about the harmful effects of smoking. In general, warnings used in different countries try to emphasize the same messages. Warnings for some countries are listed below. Such warnings have been required in tobacco advertising for many years, with the earliest mandatory warning labels implemented in the United States in 1966. [ 1 ] Implementing tobacco warning labels has been strongly opposed by the tobacco industry, most notably in Australia , following the implementation of plain packaging laws.
The WHO Framework Convention on Tobacco Control , adopted in 2003, requires such warning messages to promote awareness against smoking. [ 2 ]
The effectiveness of tobacco warning labels has been studied extensively over the past 50 years, and research shows that they are generally effective in changing smoking attitudes and behaviors. [ 3 ] [ 4 ] [ 5 ] A 2009 science review determined that there is "clear evidence that tobacco package health warnings increase consumers' knowledge about the health consequences of tobacco use". The warning messages "contribute to changing consumers' attitudes towards tobacco use as well as changing consumers' behavior". [ 6 ]
Despite the demonstrated benefits of warning labels, the efficacy of fear-based messaging in reducing smoking behaviors has been subject to criticism. [ 7 ] [ 8 ] A 2007 meta-analysis demonstrated that messages emphasizing the severity of threat may be less effective at changing behaviors than messages focusing on susceptibility to threat, [ 9 ] suggesting that extremely graphic warning labels are no more effective than labels that simply state the negative consequences of a behavior. Additionally, the study found that warning labels may not be effective among smokers who are not confident that they can quit, leading the authors to recommend exploring other methods of behavior modification . [ 10 ]
In many countries, a variety of warnings with graphic, disturbing images of tobacco-related harms (including hematuria and diabetes ) are placed prominently on cigarette packages.
As of 2020, all tobacco products in Albania must have one of the following general warning on the packaging: "Smoking kills - quit now" or "Smoking kills". [ 11 ] Additionally, packaging must contain an information message about the product, as follows: "Tobacco contains over 70 substances that cause cancer ". The general warning and the information message must occupy 50% of the packaging area of the side on which they are printed. Albania also requires the use of combined warnings that includes the text warning and a colored image, which must cover 65% of the front and back area of the packaging.
Text-based general warning label used on tobacco packages in Albania:
General warning (former):
As of 30 January 2013 Argentina passed a law requiring all cigarette packages must include graphical warning labels that show the detrimental effects on the health of long-term smokers, including COVID-19 (added in 2022). [ 12 ] [ 13 ] [ 14 ]
On 1 December 2012, Australia introduced ground-breaking legislation and the world's toughest tobacco packaging warning messages to date. [ 15 ] All marketing and brand devices were removed from the package and replaced with warnings, only the name of the product remains in generic standard sized text. All tobacco products sold, offered for sale or otherwise supplied in Australia were plain-packaged and labelled with new and expanded health warnings. [ 16 ] [ 17 ]
In Azerbaijan , a text-only health warning in the Azeri language, "Smoking harms your health", is required to cover 30% of the front and back of the package. [ 18 ] There is no requirement for rotation, and there is only one required health warning. Misleading packaging and labeling, including terms such as "light" and "mild," is prohibited.
Bangladesh law requires rotating pictorial health warnings to cover at least 50% of the main display areas of all tobacco products. [ 19 ] Misleading terms such as "light" and "low tar " are prohibited on tobacco packaging, but other misleading packaging (e.g., colors, numbers, and symbols) is not banned.
Belgium became a Party to the WHO Framework Convention on Tobacco Control on January 30, 2006. [ 20 ] Belgium implemented their current health warnings policy starting April 2007.
Including the border, health warnings cover 48% of the front and 63% of the back of cigarette packages, which is larger than the EU requirements of 35% front and 50% back because Belgium is a trilingual country ( German , French , Flemish ). Overall, 56% of the package space is appropriated to health warnings. Since 2011, three different sets of 14 warnings have been rotated every 12 months.
Belgium prohibits the terms "light" and "mild" from appearing on packages.
Additionally, Belgium requires tar, nicotine , and carbon monoxide emission numbers to appear on the side of packages. These emission numbers are generated using the ISO machine smoking method.
In Bolivia , a variety of warnings with graphic, disturbing images of tobacco-related harms (including laryngeal cancer and heart attack ) are placed prominently on cigarette packages.
Bosnia and Herzegovina law requires:
Front of packaging (covers 30% of surface):
Back of packaging (covers 50% of surface):
Before 2011, a small warning with the text Pušenje je štetno za zdravlje (Smoking is harmful to health) was printed on the back of cigarette packets.
In 2001, Brazil became the second country in the world and the first country in Latin America to adopt mandatory warning images in cigarette packages. [ 21 ] Warnings and graphic images illustrating the risks of smoking occupy 100% of the back of cigarette packs. In 2008, the government enacted a third batch of images [ 22 ] aimed at younger smokers. [ 21 ] The rule was in force for nine years until 2017, when yet another batch of warnings were introduced. They contain images as equally disturbing as the previous ones but also contain subtle messages such as "Você morre" ( You die ), "Você sofre" ( You suffer ) and "Você adoece" ( You get sick ).
Since 2003, the sentence
Este produto contém mais de 4,7 mil substâncias tóxicas, e nicotina que causa dependência física ou psíquica. Não existem níveis seguros para consumo dessas substâncias. (This product contains over 4,700 toxic substances and nicotine, which causes physical or psychological addiction. There are no safe levels for consuming these substances.)
is displayed in all packs.
The following warnings appear on cigarette packages in Brunei since 2007: [ 23 ] [ 24 ] [ 25 ]
In Cambodia , a variety of warnings with graphic, disturbing images of tobacco-related harms (including premature birth and lung cancer) are placed prominently on cigarette packages.
Canada has had three phases of tobacco warning labels. The first set of warnings was introduced in 1989 under the Tobacco Products Control Act, and required warnings to be printed on all tobacco products sold legally in Canada. The set consisted of four messages printed in black-and-white on the front and back of the package, and was expanded in 1994 to include eight messages covering 25% of the front top of the package. [ 26 ]
In 2000, the Tobacco Products Information Regulations (TPIR) were passed under the Tobacco Act . The regulations introduced a new set of sixteen warnings. Each warning was printed on the front and back of the package, covering 50% of the surface, with a short explanation and a picture illustrating that particular warning, for example:
CIGARETTES CAUSE LUNG CANCER 85% of lung cancers are caused by smoking. 80% of lung cancer victims die within three years.
accompanied by a picture of cancerous growths inside a human lung.
Additionally, on the inside of the packaging or, for some packets, on a pull-out card, "health information messages" provide answers and explanations regarding common questions and concerns about quitting smoking and smoking-related illnesses. The side of the package also featured information on toxic emissions and constituent levels. [ 27 ]
In 2011, the TPIR were replaced for cigarettes and little cigars with the Tobacco Products Labelling Regulations (Cigarettes and Little Cigars). These regulations introduced the third and current set of 16 warnings in Canada. Currently, cigarette and little cigar packages in Canada must bear new graphic warning messages that cover 75% of the front and back of the package. The interior of each package contains 1 of 8 updated health warning messages, all including the number for a national quitline. The side of the package now bears 1 of 4 simplified toxic emission statements. These labels were fully implemented on cigarette and little cigar packages by June 2012 (though the 2000 labels still appear on other tobacco products). Canada also prohibits terms such as "light" and "mild" from appearing on tobacco packaging. [ 27 ] The current labels were based on extensive research and a long consultation process that sought to evaluate and improve upon the warnings introduced in 2000. [ 28 ]
In accordance with Canadian law regarding products sold legally in Canada, the warnings are provided in both English and French . Imported cigarettes to be sold in Canada which do not have the warnings are affixed with sticker versions when they are sold legally in Canada.
Health Canada considered laws mandating plain packaging , legal tobacco product packaging did still include warning labels, but brand names, fonts, and colors were replaced with simple unadorned text, thereby reducing the impact of tobacco industry marketing techniques. [ 29 ]
There have been complaints from some Canadians due to the graphic nature of the labels. [ who? ] It was mandated in January 2020.
Canada became the first country in the world to require health warnings on each individual cigarettes and cigars, effective August 1, 2023, to be phased in over time when the regulation is fully in effect by April 2025. [ 30 ]
Starting in November 2006, all cigarette packages sold in Chile are required to have one of two health warnings, a graphic pictorial warning or a text-only warning. These warnings are replaced with a new set of two warnings each year. [ 31 ]
Under laws of the People's Republic of China , the Law on Tobacco Monopoly (中华人民共和国烟草专卖法) Chapter 4, Article 18 and Regulations for the Implementation of the Law on Tobacco Monopoly (中华人民共和国烟草专卖法实施条例) Chapter 5 Article 29, cigarettes and cigars sold within Mainland China should indicate the grade of tar content and "Smoking is hazardous to your health" (吸烟有害健康) in the Chinese language on the packs and cartons.
In 2009, the warnings were changed. The warnings, which occupy not less than 30% of the front and back of cigarette packs, show "吸烟有害健康 尽早戒烟有益健康" (Smoking is harmful to your health. Quitting smoking early is good for your health) in the front and "吸烟有害健康 戒烟可减少对健康的危害" (Smoking is harmful to your health. Quitting smoking can reduce health risks) in the back.
The warnings were revised in October 2016 and must occupy at least 35% of the front and back of cigarette packs. The following are the current warnings.
In Colombia , a variety of warnings with graphic, disturbing images of tobacco-related harms (including clogged arteries and bladder cancer ) are placed prominently on cigarette packages.
In Costa Rica , a variety of warnings with graphic, disturbing images of tobacco-related harms (including lung cancer and heart attack) are placed prominently on cigarette packages.
Timor-Leste only used a text warning, "FUMA OHO ITA" (Smoking kills), prior to 2018, when new pictorial warnings covering 85% of the front and 100% of the back of packages were implemented. [ 32 ] [ 33 ] [ 34 ]
The warnings currently in use are:
In Ecuador , a variety of warnings with graphic, disturbing images of tobacco-related harms (including tongue cancer and premature birth) are placed prominently on cigarette packages.
In Egypt , a variety of warnings with graphic, disturbing images of tobacco-related harms (including mouth cancer and gangrene ) are placed prominently on cigarette packages.
Cigarette packets and other tobacco packaging must include warnings in the same size and format and using the same approved texts (in the appropriate local languages) in all member states of the European Union .
These warnings are displayed in black Helvetica bold on a white background with a thick black border. Ireland once prefaced its warnings with "Irish Government Warning", Latvia with "Veselības ministrija brīdina" ( Health Ministry Warning ) and Spain with "Las autoridades sanitarias advierten" ("The Health Board Warns"). In member states with more than one official language, the warnings are displayed in all official languages, with the sizes adjusted accordingly (for example in Belgium the messages are written in Dutch, French and German, in Luxembourg in French and German and in Ireland, in Irish and English). All cigarette packets sold in the European Union used to have to display the content of nicotine , tar , and carbon monoxide in the same manner on the side of the packet, this is no longer the case.
In 2003, it was reported that sales of cigarette cases had surged, attributable to the introduction of more prominent warning labels on cigarette packs by an EU directive in January 2003. [ 35 ] Alternatively, people choose to hide the warnings using various "funny" stickers, such as "You could be hit by a bus tomorrow." [ 35 ]
The most recent EU legislation is the Tobacco Products Directive , which became applicable in EU countries in May 2016. [ 36 ]
In Belgium, warning signs are written in Dutch, French and German, the three official languages of Belgium.
Croatia requires:
Front of packaging (covers 30% of surface):
or
Back of packaging (covers 40% of surface):
The last warning contains a mistranslation from Directive 2001/37/EC – "hydrogen" was translated as ugljik (carbon) instead of vodik . It was nevertheless signed into law and started appearing on cigarette packages in March 2009.
2004–2009 These warnings were also simple text warnings.
Front of packaging:
Back of packaging:
Side of packaging:
1997–2004 Between 1997 and 2004, a simple text label warning, Pušenje je štetno za zdravlje (Smoking is harmful to health), was used.
or
As of 7 December 2016, all packages must also include warning images additionally to text warnings. Also cigarette manufacturers are prohibited to display the content of nicotine, tar and carbon monoxide on cigarette packages, because it might mislead customers. The box previously containing the contents of the cigarette was replaced by a warning message: Tabákový kouř obsahuje přes 70 látek, které prokazatelně způsobují rakovinu. (Tobacco smoke contains over 70 substances, which provably cause cancer.) [ 36 ] [ 37 ] [ 38 ]
Warning texts in tobacco products, health warnings, which are reproduced on the packaging of cigarettes and other tobacco products. It is implemented in an effort to strengthen public knowledge about the dangers of smoking.
The order was introduced in Denmark on 31 December 1991. The Order was last revised on 2 October 2003, which also imposed ban on the words "light" and "mild" on Danish cigarette packages, as did European Union countries.
The marking shall appear on one third of the most visible part of the package.
For smokeless tobacco use above markings does not, whereas the label " Denne tobaksvare kan være sundhedsskadelig og er afhængighedsskabende " (This tobacco product can damage your health and is addictive) is always used for such products.
General warning:
or
In Finland , warning signs are written in both Finnish and Swedish languages.
Before January 2017, France used regular EU warnings for tobacco products.
or
Plain packaging has been regulated since January 2017.
Ireland currently follows EU standards (see above), but previously ran its own scheme, where one of 8 messages was placed on the pack, as defined in SI 326/1991. [ 39 ]
After a High Court settlement in January 2008, it was accepted that the warnings on tobacco products must appear in both official languages of the state. [ 40 ] As a result, the European Communities (Manufacture, Presentation
and Sale of Tobacco Products) (Amendment) Regulations 2008 were put in place. [ 41 ] This provides that tobacco products going to market after 30 September 2008 must carry warnings in Irish and English . A year-long transition period applied to products which were on the market prior to 1 October 2008, which may have been sold until 1 October 2009.
Each packet of tobacco products must carry:
Other text is sometimes placed in the packets; for example, some packets contain leaflets which have all the above warnings written on them, with more detailed explanations and reasons to give up, and advice from Philip Morris .
General warning:
or
Front of packaging (covers 30% of surface):
or
There are also warnings on the back of every packet:
General warning (on the front of cigarette packages, covering at least 40% of the area):
Additional warnings (on the back of cigarette packages, covering at least 50% of the area):
or
In Spain , cigarette packages are preceded by warnings on both sides of the package marked "Las Autoridades Sanitarias advierten" (Health authorities warn), written in black and white above the black part of the standard warning.
or
General warnings on all cigarette packagings in Sweden have been in force since 1977.
General warning:
Warnings in Ghana are compliant with the EU's legislations, as follows:
Packaging 1 (same as in the newer UK packaging):
Packaging 2 (same as in the older UK packaging):
Packaging 3 (same as in the older UK packaging):
In Honduras , a variety of warnings with graphic, disturbing images of tobacco-related harms (including a lung cancer and throat cancer) are placed prominently on cigarette packages.
Under Hong Kong Law , Chap 371B Smoking (Public Health) (Notices) Order , packaging must indicate the amount of nicotine and tar that is present in cigarette boxes in addition to graphics depicting different health problems caused by smoking in the size and ratio as prescribed by law. The warnings are to be published in both official languages, Traditional Chinese and English.
Every warning begins with the phrase ' 香港特區政府忠告市民 /HKSAR GOVERNMENT WARNING' and then one of the following in all caps:
In addition, any print advertisement must give minimum 85% coverage of the following warnings:
HKSAR GOVERNMENT HEALTH WARNING
In 2018, a new batch of warnings were introduced, consisting of the following warnings that cover 85% of packs:
All cigarette packets and other tobacco packaging in Iceland must include warnings in the same size and format as in the European Union and using the same approved texts in Icelandic .
General warning:
These warnings are also used:
Cigarette packets sold in India are required to carry graphical and textual health warnings. The warning must cover at least 85% of the surface of the pack, of which 60% must be pictorial and the remaining 25% contains textual warnings in English, Hindi or any other Indian language.
In 2003, India ratified the World Health Organisation's Framework Convention on Tobacco Control , which includes a recommendation for large, clear health warnings on tobacco packages. However, there was a delay in implementing graphic warning labels. [ 42 ]
Until 2008, [ 43 ] cigarette packets sold in India were required to carry a written warning on the front of the packet with the text CIGARETTE SMOKING IS INJURIOUS TO HEALTH in English. Paan, gutkha and tobacco packets carried the warning TOBACCO IS INJURIOUS TO HEALTH in Hindi and English. The law later changed. According to the new law, cigarette packets were required to carry pictorial warnings of a skull or scorpion along with the text SMOKING KILLS and TOBACCO CAUSES MOUTH CANCER in both Hindi and English.
The Cigarette and Other Tobacco Products (Packaging and Labelling) Rules 2008 requiring graphic health warnings came into force on 31 May 2008. Under the law, all tobacco products were required to display graphic pictures, such as pictures of diseased lungs, and the text SMOKING KILLS or TOBACCO KILLS in English , covering at least 40% of the front of the pack, and retailers must display the cigarette packs in such a way that the pictures on pack are clearly visible. In January 2012, controversy arose when it was discovered that an image of former English footballer John Terry was used on a warning label. [ 44 ]
On 15 October 2014, Union Health Minister Harsh Vardhan announced that only 15% of the surface of a pack of cigarettes could contain branding, and that the rest must be used for graphic and text health warnings. [ 45 ] The Union Ministry of Health amended the Cigarettes and Other Tobacco Products (Packaging and Labelling) Rules, 2008 to enforce the changes effective from 1 April 2015. [ 43 ] [ 46 ] [ 47 ]
However, the government decision to increase pictorial warnings on tobacco packets from 1 April was put on hold indefinitely, following the recommendations of a Parliamentary committee, which reportedly did not speak to health experts but only to tobacco lobby representatives. [ 48 ] On 5 April 2016, the health ministry ordered government agencies to enforce this new rule. [ 49 ]
Following the intervention by the Parliamentary committee, NGO Health of Millions, represented by Prashant Bhushan , filed a petition in the Supreme Court of India , which asked the government to stop selling of loose cigarettes and publish bigger health warnings on tobacco packs. [ 50 ]
In Indonesia , tobacco warnings are not just placed on packages but also on cigarette advertisements , which are not banned in few countries including Indonesia.
With the enforcement of Indonesian Government Regulation No. 19 (2000), a new warning was implemented:
The last recorded usage of this warning in TV advertisements was an Esse Mild advertisement from late February 2014. [ 51 ]
With the enforcement of the Indonesian Government Regulation No. 109 (2012), all tobacco products/cigarette packaging and advertisement should include warning images and age restriction (18+). Graphic warnings must cover 40% of cigarette packages. After the introduction of graphic images in Indonesian cigarette packaging, the branding of cigarettes as "light", "mild", "filter", etc. is forbidden, except for brands that already use some words above such as L.A. Lights, A Mild or Dunhill Filter. However, the last advertisement to use this warning was a 2021 Djarum Super advertisement, before it subsequently used the 2018 warning. [ 52 ]
Other alternatives:
These warnings below appear on the side of cigarette packaging:
After it was revealed that the pictorial warnings used in Indonesia originally came from the 2005 warnings of Thailand, [ 54 ] on 31 May 2018, the Ministry of Health launched new pictorial health warnings, of which two depict Indonesian smokers and one depicts a smoker from Venezuela. [ 55 ] [ 56 ]
Other alternatives:
In Iran , a variety of warnings with graphic, disturbing images of tobacco-related harms (including lung cancer and mouth cancer) are placed prominently on cigarette packages.
Additionally, many cigarette packs contain a writing under the image which says "ترک سیگار موجب سلامتی و افزایش طول عمرمیشود" and in English it roughly means "quitting cigarettes makes you healthier and increases lifespan".
In 1972, Japan became the first country in Asia to display a general warning on cigarette packages.
Prior to 2005, there was only one warning on all Japanese cigarette packages.
Since 2005, more than one general warning is printed on cigarette packaging.
On the front of cigarette packages:
On the back of cigarette packages:
In Laos , a variety of warnings with graphic, disturbing images of tobacco-related harms (including mouth cancer and rotting teeth) are placed prominently on cigarette packages.
In Malaysia , general warning as a mandatory on all Malaysian cigarette packaging are in force since June 1976. [ 57 ]
Starting 1 June 2009, the Malaysian government has decided to place graphic images on the cigarette packs to show the adverse long-term effects of excessive smoking, replacing the general warning with text describing the graphic images printed in Malay (front) and English (back) explaining:
Graphic warning messages must consist 40% of the front of cigarette packages and 60% in the back. After the introduction of graphic images in Malaysian cigarette packaging, the branding of cigarettes as "light", "mild", etc. is forbidden.
In the Maldives , products containing tobacco are required by law to have (in Dhivehi ): [ 58 ]
At the front and back:
On the sides:
Since 2010, cigarette packs in Mexico must contain health warnings and graphic images. By law, 30% of the pack's front, 100% of the pack's rear and 100% of one lateral must consist on images and warnings. The Secretariat of Health issues new warnings and images every six months. Images have included a dead rat, a partial mastectomy, a laryngectomy, a dead human fetus surrounded by cigarette butts, a woman being fed after suffering a stroke and damaged lungs, amongst others.
Warnings include smoking-related diseases and statistics, toxins found in cigarettes and others.
Mexico became the first country to put a warning on cigarette packs that tobacco use could increase the risk of COVID-19 infection. [ 59 ]
General warning (on the front of cigarette packages, covering at least 30% of the area, Helvetica font):
Additional warnings (on the back of cigarette packages, covering at least 40% of the area, Helvetica font):
Regulated by "Lege cu privire la tutun şi la articolele din tutun" (Law on tobacco and tobacco articles) nr. 278-XVI from 14.12.2007 [ 60 ] enabled at 07.03.2008
There is no such rule in Transnistria , where cigarette packages have variable warning labels depending on where they come from.
The first health warnings appeared on cigarette packets in New Zealand in 1974. Warning images accompanying text have been required to appear on each packet since 28 February 2008. New regulations were made on 14 March 2018 which provided for larger warnings and a new schedule of images and messages. [ 61 ]
By law, [ 61 ] 75% of a pack's front and 100% of its rear must consist of warning messages. Images include gangrenous toes, rotting teeth and gums, diseased lungs and smoking-damaged hearts. Cigarette packets also carry the New Zealand Quitline logo and phone number and other information about quitting smoking. [ 62 ]
In total, there are 15 different warnings. A full list with pictures is available at the New Zealand Ministry of Health's website . Warning messages are rotated annually. The following is a list of the warnings in English and Māori.
Six warnings existed prior to 2013:
From 2013 onwards, the general warning in Nigeria is: The Federal Ministry of Health warns that smokers are liable to die young.
North Korea signed the WHO Framework Convention on Tobacco Control on 17 June 2003 and ratified it on 27 April 2005. [ 63 ] Tobacco packaging warning messages are required on all types of packaging, but their appearance is not regulated in any way. [ 64 ] They are usually printed in small print on the side of the package and only state that smoking is harmful to health. [ 65 ] However, the descriptions must state the nicotine and tar content, [ 66 ] must not be misleading and do need to be approved by local authorities. [ 67 ] Graphic warning images that are now common worldwide have never appeared on packaging in North Korea. [ 68 ]
Norway has had general warnings on cigarette packets since 1975. Norway's warnings of today were introduced in 2003 and are in line with the European Union's legislation, as Norway is an EEA member:
On the front of cigarette and cigar packages, covering about 30% of the area:
On the back of cigarette and cigar packages, covering about 45% of the area:
Tobacco products like snus and chewing tobacco have the following warning printed on them:
All cigarette packages in Pakistan are required by Statutory Order 1219(I)/2008 dated 25 September 2008, published in The Gazette of Pakistan dated 24 November 2008, to carry rotating health warnings from 1 July 2009.
Each health warning is printed for a period of 6 months, covering at least 30% on both sides of the packet and must be printed in Urdu at the front and English at the back. The warnings in English currently in use are:
In Panama , a variety of warnings with graphic, disturbing images of tobacco-related harms (including throat cancer and lung cancer) are placed prominently on cigarette packages.
In Paraguay , a variety of warnings with graphic, disturbing images of tobacco-related harms (including impotence and heart attack) are placed prominently on cigarette packages.
In Peru , a variety of warnings with graphic, disturbing images of tobacco-related harms (including abortions and asthma) are placed prominently on cigarette packages.
All cigarette packaging sold in the Philippines are required to display a government warning label. The warnings include:
In July 2014, President Benigno Aquino III signed the Republic Act 10643, or "An Act to Effectively Instill Health Consciousness through Graphic Health Warnings on Tobacco Products", more known as the "Graphic Health Warning Act." This law requires tobacco product packaging to display pictures of the ill effects of smoking, occupying the bottom half of the display area in both front and the back side of the packaging. [ 69 ] On 3 March 2016, Department of Health (DOH) secretary Janette Garin started the implementation of Republic Act 10643, requiring tobacco manufacturers to include graphic health warnings on newer cigarette packaging. [ 70 ]
With the Graphic Health Warning Act implemented, graphic health warnings are used on all newer cigarette packages and older packages using text-only warnings are required to be replaced by newer ones incorporating graphic warnings. [ 71 ] The 12 new warnings, showing photos of negative effects of smoking, like mouth cancer, impotence and gangrene are rotated every two years, [ 72 ] and on 3 November 2016, all cigarette packaging without graphic health warning messages are banned from sale. [ 71 ] Labeling of cigarettes with "light" or "mild" is also forbidden by the Graphic Health Warning Act. [ 73 ]
Warning messages on Russian cigarette packets were revised in 2013, falling in line with European Union standards.
12 different variants are used. [ 74 ]
The warning messages cigarette packets in Serbia are visually similar to what is used in European Union countries, but the texts used in Serbia are not translated from EU-approved texts.
Singapore used blunt, straight-to-the-point messages such as "Smoking causes lung cancer" as text warnings on cigarette packets. They were later replaced by graphic warnings in August 2004, with gory pictures and the following messages:
In 2016, the images and warnings were revised, with images focusing mostly on damaged organs. The following warnings show what is printed nowadays.
From 1 January 2009, people possessing cigarettes without the SDPC ( S ingapore D uty P aid C igarettes) label will be committing an offence under the Customs and GST Acts. The law was passed to distinguish non-duty paid, contraband cigarettes from duty-paid ones.
A small warning, in Somali and English, is printed on Somali cigarette packages.
In South Africa , the Tobacco Products Control Act, 1993 and its amendments (1999, 2007, 2009), stipulate that a warning related to the harmful effects (health, social, or economic) of tobacco smoking, or the beneficial effects of cessation, must be placed prominently on tobacco products covering 15% of the obverse, 25% of the reverse and 20% of the sides of packs. [ 75 ] [ 76 ]
According to the draft Control of Tobacco Products and Electronic Delivery Systems Bill , 2018, new legislation, once enacted, will require uniform, plain-colored packaging (branding and logos prohibited) containing the brand and product name in a standard typeface and color, a warning related to the harmful effects of tobacco smoking, or beneficial effects of cessation, and a graphic image of tobacco-related harm. [ 77 ]
In South Korea , general warnings on cigarette packaging have been used since 1976. The warning messages used since then have been:
Front : 흡연은 폐암 등 각종 질병의 원인이 되며, 특히 임신부와 청소년의 건강에 해롭습니다 (Smoking causes lung cancer and other diseases and it is especially dangerous for teenagers and pregnant women)
Back : 19세 미만 청소년에게 판매할 수 없습니다 (It is illegal to sell cigarettes to people under 19) and additionally, 금연하면 건강해지고 장수할 수 있습니다 (You can be healthy and live longer if you quit), 흡연은 중풍과 심장병도 일으킵니다 (Smoking also causes paralysis and heart diseases), 흡연은 사랑하는 자녀의 건강도 해칩니다 (Smoking also damages your beloved children), 당신이 흡연하면 다른 사람의 건강도 해칩니다 (Smoking damages others)
Front : 건강을 해치는 담배 그래도 피우시겠습니까? (Smoking damages your health. Do you still want to smoke?)
Back : 19세 미만 청소년에게 판매할 수 없습니다 (It is illegal to sell cigarettes to people under 19) and additionally, 금연하면 건강해지고 장수할 수 있습니다 (You can be healthy and live longer if you quit), 흡연은 중풍과 심장병도 일으킵니다 (Smoking also causes paralysis and heart diseases), 흡연은 사랑하는 자녀의 건강도 해칩니다 (Smoking also damages your beloved children), 당신이 흡연하면 다른 사람의 건강도 해칩니다 (Smoking hurts others)
Front , 흡연은 폐암 등 각종 질병의 원인이 되며, 특히 임신부와 청소년의 건강에 해롭습니다 (Smoking causes lung cancer and other diseases and it is especially dangerous for teenagers and pregnant women)
Back : 19세 미만 청소년에게 판매 금지! 당신 자녀의 건강을 해칩니다" (It is illegal to sell cigarettes to people under 19! It hurts your children's health)
Front : 건강에 해로운 담배, 일단 흡연하게 되면 끊기가 매우 어렵습니다 (Smoking damages your health. Once you start smoking, it is very difficult to quit)
Back : 19세 미만 청소년에게 판매 금지! 당신 자녀의 건강을 해칩니다 (It is illegal to sell cigarettes to people under 19! It hurts your children's health)
In Sri Lanka, a variety of warnings with graphic, disturbing images of tobacco-related harms (including cancer and heart attack) are placed prominently on cigarette packages.
Switzerland has warning messages in its three official languages (German, French and Italian). The three warning messages below, all meaning "Smoking kills", are posted on cigarette packs until 2024:
Since October 2024, the Federal Act on Tobacco Products updated the warnings to "Smoking kills – stop now":
The warnings in Taiwan are led by the phrase "行政院衛生署警告" ( Warning from the Department of Health , Executive Yuan : ) and followed by one of the following warnings:
The images and warnings were revised in 2014, after the Department of Health was reorganised into the Ministry of Health and Welfare. The following warnings show what is printed since 1 June 2014. [ 80 ]
Warnings of any version are accompanied with "戒煙專線: 0800-636363" (Smoking Quitline: 0800–636363).
In Thailand , a variety of warnings with graphic, disturbing images of tobacco-related harms (including a tracheotomy and rotting teeth) are placed prominently on cigarette packages. [ 81 ] A recent study showed that the warnings made Thai smokers think more often about the health risks of smoking and about quitting smoking.
Thailand introduced plain packaging in 2020. [ 82 ]
or
The warning messages on cigarette packets in Ukraine are also visually similar to those in European Union countries:
In 1971, tobacco companies printed on the left side of cigarette packets an official warning: "Warning by H.M. Government – Smoking can harm your health", followed by the phrase " Health Department 's Chief Medical Officers", issuers of the warning.
In 1991, the EU tightened laws on tobacco warnings. Thus, the message "Tobacco seriously damages health" was printed on the front of all tobacco packs. An additional warning was also printed on the reverse of cigarette packs.
In 2003, new EU regulations required one of the following general warnings must be displayed, covering at least 30% of the surface of the pack:
Additionally, one of the following additional warnings must be displayed, covering at least 40% of the surface of the pack:
From October 2008, all cigarette products manufactured must carry picture warnings in the reverse. Every pack must have one of these warnings by October 2009.
Plain packaging, including prominent and standardised health warnings and minimal manufacturer information, became compulsory for all cigarette and hand-rolling tobacco packs manufactured after May 2016 and sold after May 2017. [ 83 ]
In 1966, the United States became the first nation in the world to require a health warning on cigarette packages. [ 85 ] [ 86 ]
In 1973, the assistant director of Research at R.J. Reynolds Tobacco Company wrote an internal memorandum regarding new brands of cigarettes for the youth market. He observed that, "psychologically, at eighteen, one is immortal" and theorized that "the desire to be daring is part of the motivation to start smoking." He stated, "in this sense the label on the package is a plus." [ 87 ]
In 1999, Philip Morris USA purchased three brands of cigarettes from Liggett Group Inc. The brands were: Chesterfield , L&M , and Lark . [ 88 ] At the time Philip Morris purchased the brands from Liggett, the packaging for those cigarettes included the statement "Smoking is Addictive". After Philip Morris acquired the three Liggett brands, it removed the statement from the packages. [ 89 ]
Though the United States started the trend of labeling cigarette packages with warnings, today the country has one of the least restrictive labelling requirements on their packages. [ 90 ] Warnings are usually in small typeface placed along one of the sides of the cigarette packs with colors and fonts that closely resemble the rest of the package, so the warnings essentially are integrated and do not stand out with the rest of the cigarette package. [ 90 ]
However, this is subject to change as the Family Smoking Prevention and Tobacco Control Act of 2009 requires color graphics with supplemental text that depicts the negative consequences of smoking to cover 50% of the front and rear of each pack. The nine new graphic warning labels were announced by the FDA in June 2011 and were required to appear on packaging by September 2012, though this was delayed by legal challenges. [ 91 ]
In August 2011, five tobacco companies filed a lawsuit against the FDA in an effort to reverse the new warning mandate. Tobacco companies claimed that being required to promote government anti-smoking campaigns by placing the new warnings on packaging violates the companies' free speech rights. [ 92 ] Additionally, R.J. Reynolds , Lorillard , Commonwealth Brands Inc. , Liggett Group LLC and Santa Fe Natural Tobacco Company Inc. claimed that the graphic labels are an unconstitutional way of forcing tobacco companies to engage in anti-smoking advocacy on the government's behalf. [ 93 ] A First Amendment lawyer, Floyd Abrams , represented the tobacco companies in the case, contending that requiring graphic warning labels on a lawful product cannot withstand constitutional scrutiny. [ 94 ] The Association of National Advertisers and the American Advertising Federation also filed a brief in the suit, arguing that the labels infringe on commercial free speech and could lead to further government intrusion if left unchallenged. [ 95 ]
On 29 February 2012, US District Judge Richard Leon ruled that the labels violate the right to free speech in the First Amendment . [ 96 ] However, the following month the US Court of Appeals for the 6th Circuit upheld the majority of the Tobacco Control Act of 2009, including the part requiring graphic warning labels. In April 2013 the Supreme Court declined to hear the appeal to this ruling, allowing the new labels to stand. As the original ruling against the FDA images was not actually reversed, the FDA will again need to go through the process of developing the new warning labels, and the timetable and final product remain unknown. Additionally, rulings of the 6th Circuit are precedential only in the states comprising the 6th Circuit, i.e., Michigan, Ohio, Kentucky, and Tennessee. [ 97 ] [ 98 ] [ 99 ] [ 100 ]
In March 2020, the FDA approved a set of 11 new graphic warning labels with images for cigarette packaging, with a deadline of compliance being set to June 18, 2021. The mandate would have required packaging to cover the top 50% of the front and rear panels of packages, as well as at least 20% of the top. Tobacco manufacturers R.J. Reynolds Tobacco Co., Philip Morris USA, ITG Brands LLC and Liggett Group LLC filed a joint motion requesting a preliminary injunction on implementing the labels and a ruling to prohibit enforcement in April 2020. They argued that the new packaging would have been a violation of the First Amendment . In December 2022, U.S. district judge J. Campbell Barker of the Eastern District of Texas ordered the new guidelines to be vacated, arguing the multiple interpretation of images cannot prove neutrality. The deadline was pushed to November 6, 2023. [ 101 ] The decision was later appealed and overturned by a U.S. Appeals court who ruled unanimously that the warnings where "factual and uncontroversial" and thus was not in violation of the first amendment. [ 102 ] The decision was later appealed again to the U.S. Supreme Court however they declined to hear the case, thus making the new packaging legal. [ 103 ] In September 2024 the FDA announced that Enforcement of the new packaging would begin on December 12, 2025. [ 104 ]
Stronger warning labels started to appear in May 2010, but are yet to be officially implemented.
Effective June 2010, the following labels began to appear on smokeless tobacco products (most of which are chewing tobacco ) and their advertisements.
These warnings are required to comprise 30% of two principal display panels on the packaging; on advertisements, the health warnings must constitute 20% of the total area. [ 105 ]
In Uruguay , a variety of warnings with graphic, disturbing images of tobacco-related harms (including lung cancer and mouth cancer) are placed prominently on cigarette packages.
Since 1978 in Venezuela , the only warning in cigarette packs was printed in a very small typeface along one of the sides:
" Se ha determinado que el fumar cigarrillos es nocivo para la salud – Ley de impuesto sobre cigarrillos " (It has been determined that cigarette smoking is harmful to your health – Cigarette Tax Law)
On 24 March 2005, another warning was introduced in every cigarette pack, similar to what was implemented in Brazil: "Este producto contiene alquitrán, nicotina y monóxido de carbono, los cuales son cancerígenos y tóxicos. No existen niveles seguros para el consumo de estas sustancias" ("This product contains tar, nicotine and carbon monoxide, which are carcinogenic and toxic. There are no safe levels for consumption of these substances").
The 1978 warning was not removed, so now every cigarette pack contains both warnings (one on each side).
In addition, since 24 March 2005, as part of the "Venezuela 100% libre de humo" (100% smoke-free Venezuela) campaign, one of the following warnings is randomly printed very prominently, along with a graphical image, occupying 100% of the back of the pack (40% for the text warning and 60% for the image):
Curiously, these warnings only appear on cigarette packs and not on other tobacco products (which only use the 1978 warning).
The following warnings appear on cigarette packages in Vietnam since 2013, along with graphic, disturbing images of tobacco-related harms: | https://en.wikipedia.org/wiki/Tobacco_packaging_warning_messages |
Tobacco smoke is a sooty aerosol produced by the incomplete combustion of tobacco during the smoking of cigarettes and other tobacco products. Temperatures in burning cigarettes range from about 400 °C between puffs to about 900 °C during a puff. During the burning of the cigarette tobacco (itself a complex mixture), thousands of chemical substances are generated by combustion, distillation , pyrolysis and pyrosynthesis . [ 1 ] [ 2 ] Tobacco smoke is used as a fumigant and inhalant .
The particles in tobacco smoke are liquid aerosol droplets (about 20% water), with a mass median aerodynamic diameter (MMAD) that is submicrometer (and thus, fairly "lung-respirable" by humans). The droplets are present in high concentrations (some estimates are as high as 10 10 droplets per cm 3 ).
Tobacco smoke may be grouped into a particulate phase (trapped on a glass-fiber pad, and termed "TPM" (total particulate matter)) and a gas/vapor phase (which passes through such a glass-fiber pad). "Tar" is mathematically determined by subtracting the weight of the nicotine and water from the TPM. However, several components of tobacco smoke (e.g., hydrogen cyanide , formaldehyde , phenanthrene , and pyrene ) do not fit neatly into this rather arbitrary classification, because they are distributed among the solid, liquid and gaseous phases. [ 1 ]
Tobacco smoke contains a number of toxicologically significant chemicals and groups of chemicals, including polycyclic aromatic hydrocarbons ( benzopyrene ), tobacco-specific nitrosamines ( NNK , NNN ), aldehydes ( acrolein , formaldehyde ), carbon monoxide , hydrogen cyanide , nitrogen oxides ( nitrogen dioxide ), benzene , toluene , phenols ( phenol , cresol ), aromatic amines ( nicotine , ABP ( 4-aminobiphenyl )), and harmala alkaloids . The radioactive element polonium-210 is also known to occur in tobacco smoke. [ 1 ] The chemical composition of smoke depends on puff frequency, intensity, volume, and duration at different stages of cigarette consumption. [ 3 ]
Between 1933 and the late 1940s, the yields from an average cigarette varied from 33 to 49 mg "tar" and from less than 1 to 3 mg nicotine. In the 1960s and 1970s, the average yield from cigarettes in Western Europe and the USA was around 16 mg tar and 1.5 mg nicotine per cigarette. Current average levels are lower. [ 4 ] This has been achieved in a variety of ways including use of selected strains of tobacco plant, changes in agricultural and curing procedures, use of reconstituted sheets (reprocessed tobacco leaf wastes), incorporation of tobacco stalks, reduction of the amount of tobacco needed to fill a cigarette by expanding it (like puffed wheat ) to increase its "filling power", and by the use of filters and high-porosity wrapping papers . [ 5 ] The development of lower "tar" and nicotine cigarettes has tended to yield products that lacked the taste components to which the smoker had become accustomed. In order to keep such products acceptable to the consumer, the manufacturers reconstitute aroma or flavor. [ 3 ]
Tobacco polyphenols (e. g., caffeic acid , chlorogenic acid , scopoletin , rutin ) determine the taste and quality of the smoke. Freshly cured tobacco leaf is unfit for use because of its pungent and irritating smoke. After fermentation and aging, the leaf delivers mild and aromatic smoke. [ 6 ]
Tobacco smoke, besides being an irritant and significant indoor air pollutant , is known to cause lung cancer , heart disease , chronic obstructive pulmonary disease (COPD), emphysema , and other serious diseases in smokers (and in non-smokers as well). The actual mechanisms by which smoking can cause so many diseases remain largely unknown. Many attempts have been made to produce lung cancer in animals exposed to tobacco smoke by the inhalation route, without success. It is only by collecting the "tar" and repeatedly painting this on to mice that tumors are produced, and these tumors are very different from those tumors exhibited by smokers. [ 1 ] Tobacco smoke is associated with an increased risk of developing respiratory conditions such as bronchitis , pneumonia , and asthma . Tobacco smoke aerosols generated at temperatures below 400 °C did not test positive in the Ames assay . [ 7 ]
In spite of all changes in cigarette design and manufacturing since the 1960s, the use of filters and "light" cigarettes has neither decreased the nicotine intake per cigarette, nor has it lowered the incidence of lung cancers ( NCI , 2001; IARC 83, 2004; U.S. Surgeon General, 2004). [ 8 ] The shift over the years from higher- to lower-yield cigarettes may explain the change in the pathology of lung cancer. That is, the percentage of lung cancers that are adenocarcinomas has increased, while the percentage of squamous cell cancers has decreased. The change in tumor type is believed to reflect the higher nitrosamine delivery of lower-yield cigarettes and the increased depth or volume of inhalation of lower-yield cigarettes to compensate for lower level concentrations of nicotine in the smoke. [ 9 ]
In the United States, lung cancer incidence and mortality rates are particularly high among African American men. Lung cancer tends to be most common in developed countries, particularly in North America and Europe, and less common in developing countries, particularly in Africa and South America. [ 8 ] [ clarification needed ] | https://en.wikipedia.org/wiki/Tobacco_smoke |
Tobermorite is a calcium silicate hydrate mineral with chemical formula:
Ca 5 Si 6 O 16 (OH) 2 ·4H 2 O or
Ca 5 Si 6 (O,OH) 18 ·5H 2 O.
Two structural varieties are distinguished: tobermorite-11 Å and tobermorite-14 Å.
Tobermorite occurs in hydrated cement paste and can be found in nature as an alteration mineral in metamorphosed limestone and in skarn . It has been reported to occur in the Maqarin Area of north Jordan and in the Crestmore Quarry near Crestmore Heights , Riverside County , California .
Tobermorite was first described in 1880 for an occurrence in Scotland , on the Isle of Mull , around the locality of Tobermory . [ 3 ] [ 5 ]
Aluminum-substituted tobermorite is understood to be a key ingredient responsible for the longevity of ancient undersea Roman concrete . The volcanic ash that Romans used for construction of sea walls contained phillipsite , and an interaction with sea water caused the crystalline structures in the concrete to expand and strengthen, making that material substantially more durable than modern concrete when exposed to sea water. [ 6 ] [ 7 ] [ 8 ]
Tobermorite is often used in thermodynamical calculations to represent the pole of the most evolved calcium silicate hydrate (C-S-H). According to its chemical formula , its atomic Ca/Si or molar CaO/SiO 2 (C/S) ratio is 5/6 (0.83). Jennite represents the less evolved pole with a C/S ratio of 1.50 (9/6). | https://en.wikipedia.org/wiki/Tobermorite |
In physics , the Toda oscillator is a special kind of nonlinear oscillator . It represents a chain of particles with exponential potential interaction between neighbors. [ 1 ] These concepts are named after Morikazu Toda . The Toda oscillator is used as a simple model to understand the phenomenon of self-pulsation , which is a quasi-periodic pulsation of the output intensity of a solid-state laser in the transient regime .
The Toda oscillator is a dynamical system of any origin, which can be described with dependent coordinate x {\displaystyle ~x~} and independent coordinate z {\displaystyle ~z~} , characterized in that the evolution along independent coordinate z {\displaystyle ~z~} can be approximated with equation
where D ( x ) = u e x + v {\displaystyle ~D(x)=ue^{x}+v~} , Φ ( x ) = e x − x − 1 {\displaystyle ~\Phi (x)=e^{x}-x-1~} and prime denotes the derivative.
The independent coordinate z {\displaystyle ~z~} has sense of time . Indeed, it may be proportional to time t {\displaystyle ~t~} with some relation like z = t / t 0 {\displaystyle ~z=t/t_{0}~} , where t 0 {\displaystyle ~t_{0}~} is constant.
The derivative x ˙ = d x d z {\displaystyle ~{\dot {x}}={\frac {{\rm {d}}x}{{\rm {d}}z}}} may have sense of velocity of particle with coordinate x {\displaystyle ~x~} ; then x ¨ = d 2 x d z 2 {\displaystyle ~{\ddot {x}}={\frac {{\rm {d}}^{2}x}{{\rm {d}}z^{2}}}~} can be interpreted as acceleration ; and the mass of such a particle is equal to unity.
The dissipative function D {\displaystyle ~D~} may have sense of coefficient of the speed-proportional friction .
Usually, both parameters u {\displaystyle ~u~} and v {\displaystyle ~v~} are supposed to be positive; then this speed-proportional friction coefficient grows exponentially at large positive values of coordinate x {\displaystyle ~x~} .
The potential Φ ( x ) = e x − x − 1 {\displaystyle ~\Phi (x)=e^{x}-x-1~} is a fixed function, which also shows exponential growth at large positive values of coordinate x {\displaystyle ~x~} .
In the application in laser physics , x {\displaystyle ~x~} may have a sense of logarithm of number of photons in the laser cavity , related to its steady-state value. Then, the output power of such a laser is proportional to exp ( x ) {\displaystyle ~\exp(x)~} and may show pulsation at oscillation of x {\displaystyle ~x~} .
Both analogies, with a unity mass particle and logarithm of number of photons, are useful in the analysis of behavior of the Toda oscillator.
Rigorously, the oscillation is periodic only at u = v = 0 {\displaystyle ~u=v=0~} . Indeed, in the realization of the Toda oscillator as a self-pulsing laser, these parameters may have values of order of 10 − 4 {\displaystyle ~10^{-4}~} ; during several pulses, the amplitude of pulsation does not change much. In this case, we can speak about the period of pulsation, since the function x = x ( t ) {\displaystyle ~x=x(t)~} is almost periodic.
In the case u = v = 0 {\displaystyle ~u=v=0~} , the energy of the oscillator E = 1 2 ( d x d z ) 2 + Φ ( x ) {\displaystyle ~E={\frac {1}{2}}\left({\frac {{\rm {d}}x}{{\rm {d}}z}}\right)^{2}+\Phi (x)~} does not depend on z {\displaystyle ~z~} , and can be treated as a constant of motion. Then, during one period of pulsation, the relation between x {\displaystyle ~x~} and z {\displaystyle ~z~} can be expressed analytically: [ 2 ] [ 3 ]
where x min {\displaystyle ~x_{\min }~} and x max {\displaystyle ~x_{\max }~} are minimal and maximal values of x {\displaystyle ~x~} ; this solution is written for the case when x ˙ ( 0 ) = 0 {\displaystyle {\dot {x}}(0)=0} .
however, other solutions may be obtained using the principle of translational invariance .
The ratio x max / x min = 2 γ {\displaystyle ~x_{\max }/x_{\min }=2\gamma ~} is a convenient parameter to characterize the amplitude of pulsation. Using this, we can express the median value δ = x max − x min 1 {\displaystyle \delta ={\frac {x_{\max }-x_{\min }}{1}}} as δ = ln sin ( γ ) γ {\displaystyle \delta =\ln {\frac {\sin(\gamma )}{\gamma }}} ;
and the energy E = E ( γ ) = γ tanh ( γ ) + ln sinh γ γ − 1 {\displaystyle E=E(\gamma )={\frac {\gamma }{\tanh(\gamma )}}+\ln {\frac {\sinh \gamma }{\gamma }}-1} is also an elementary function of γ {\displaystyle ~\gamma ~} .
In application, the quantity E {\displaystyle E} need not be the physical energy of the system; in these cases, this dimensionless quantity may be called quasienergy .
The period of pulsation is an increasing function of the amplitude γ {\displaystyle ~\gamma ~} .
When γ ≪ 1 {\displaystyle ~\gamma \ll 1~} ,
the period T ( γ ) = 2 π ( 1 + γ 2 24 + O ( γ 4 ) ) {\displaystyle ~T(\gamma )=2\pi \left(1+{\frac {\gamma ^{2}}{24}}+O(\gamma ^{4})\right)~}
When γ ≫ 1 {\displaystyle ~\gamma \gg 1~} , the period T ( γ ) = 4 γ 1 / 2 ( 1 + O ( 1 / γ ) ) {\displaystyle ~T(\gamma )=4\gamma ^{1/2}\left(1+O(1/\gamma )\right)~}
In the whole range γ > 0 {\displaystyle ~\gamma >0~} , the period T ( γ ) {\displaystyle ~{T(\gamma )}~} and frequency k ( γ ) = 2 π T ( γ ) {\displaystyle ~k(\gamma )={\frac {2\pi }{T(\gamma )}}~} can be approximated by
to at least 8 significant figures . The relative error of this approximation does not exceed 22 × 10 − 9 {\displaystyle 22\times 10^{-9}} .
At small (but still positive) values of u {\displaystyle ~u~} and v {\displaystyle ~v~} , the pulsation decays slowly, and this decay can be described analytically. In the first approximation, the parameters u {\displaystyle ~u~} and v {\displaystyle ~v~} give additive contributions to the decay; the decay rate, as well as the amplitude and phase of the nonlinear oscillation, can be approximated with elementary functions in a manner similar to the period above. In describing the behavior of the idealized Toda oscillator, the error of such approximations is smaller than the differences between the ideal and its experimental realization as a self-pulsing laser at the optical bench . However, a self-pulsing laser shows qualitatively very similar behavior. [ 3 ]
The Toda chain equations of motion, in the continuous limit in which the distance between neighbors goes to zero, become the Korteweg–de Vries equation (KdV) equation. [ 1 ] Here the index labeling the particle in the chain becomes the new spatial coordinate.
In contrast, the Toda field theory is achieved by introducing a new spatial coordinate which is independent of the chain index label. This is done in a relativistically invariant way, so that time and space are treated on equal grounds. [ 4 ] This means that the Toda field theory is not a continuous limit of the Toda chain. | https://en.wikipedia.org/wiki/Toda_oscillator |
Toehold mediated strand displacement (TMSD) is an enzyme -free molecular tool to exchange one strand of DNA or RNA (output) with another strand (input). It is based on the hybridization of two complementary strands of DNA or RNA via Watson-Crick base pairing (A-T/U and C-G) and makes use of a process called branch migration . [ 1 ] Although branch migration has been known to the scientific community since the 1970s, TMSD has not been introduced to the field of DNA nanotechnology until 2000 when Yurke et al. was the first who took advantage of TMSD. [ 1 ] [ 2 ] He used the technique to open and close a set of DNA tweezers made of two DNA helices using an auxiliary strand of DNA as fuel. [ 1 ] [ 3 ] Since its first use, the technique has been modified for the construction of autonomous molecular motors, catalytic amplifiers, reprogrammable DNA nanostructures and molecular logic gates . [ 3 ] [ 4 ] It has also been used in conjunction with RNA for the production of kinetically-controlled ribosensors. [ 5 ] TMSD starts with a double-stranded DNA complex composed of the original strand and the protector strand. [ 2 ] The original strand has an overhanging region the so-called “toehold” which is complementary to a third strand of DNA referred to as the “invading strand”. The invading strand is a sequence of single-stranded DNA (ssDNA) which is complementary to the original strand. [ 3 ] [ 2 ] The toehold regions initiate the process of TMSD by allowing the complementary invading strand to hybridize with the original strand, creating a DNA complex composed of three strands of DNA. [ 3 ] [ 6 ] This initial endothermic step is rate limiting [ 1 ] and can be tuned by varying the strength (length and sequence composition e.g. G-C or A-T rich strands) of the toehold region. [ 3 ] The ability to tune the rate of strand displacement over a range of 6 orders of magnitude generates the backbone of this technique and allows the kinetic control of DNA or RNA devices. [ 4 ] After the binding of the invading strand and the original strand occurred, branch migration of the invading domain then allows the displacement of the initial hybridized strand (protector strand). [ 1 ] The protector strand can possess its own unique toehold and can, therefore, turn into an invading strand itself, starting a strand-displacement cascade . [ 2 ] [ 4 ] [ 7 ] The whole process is energetically favored and although a reverse reaction can occur its rate is up to 6 orders of magnitude slower. [ 4 ] Additional control over the system of toehold mediated strand displacement can be introduced by toehold sequestering. [ 4 ] [ 8 ] [ 9 ]
A slightly different variant of strand displacement has also been introduced using a strand displacing polymerase enzyme. [ 10 ] [ 11 ] Unlike TMSD, it used the polymerase enzyme as a source of energy and it referred to as polymerase-based strand displacement. [ 11 ]
Toehold sequestering is a technique to “mask” the toehold region, rendering its accessibility. [ 4 ] [ 3 ] There are several ways to do so but the most common approaches are hybridizing the toehold with a complementary strand [ 7 ] or by designing the toehold region to form a hairpin loop . [ 12 ] Masking and unmasking of the toehold domains together with the ability to precisely control the kinetics of the reaction makes toehold mediated strand displacement a valuable tool in the field of DNA nanotechnology [ 4 ] Moreover, biosensors based on toehold mediated strand displacement reaction are useful in single molecule detection of DNA targets and SNP discrimination. [ 13 ] | https://en.wikipedia.org/wiki/Toehold_mediated_strand_displacement |
The toeprinting assay , also known as the primer extension inhibition assay , [ 1 ] is a method used in molecular biology that allows one to examine the interactions between messenger RNA and ribosomes or RNA-binding proteins . [ 2 ] It is different from the more commonly used DNA footprinting assay. The toeprinting assay has been utilized to examine the formation of the translation initiation complex. [ 3 ]
To do a toeprint assay, one needs the mRNA of interest, ribosomes, a DNA primer , free nucleotides , and reverse transcriptase (RT), among other reagents . [ 4 ] The assay involves letting the RT generate cDNA until it gets blocked by any bound ribosomes, resulting in shorter fragments called toeprints when the results are observed on a sequencing gel . | https://en.wikipedia.org/wiki/Toeprinting_assay |
Tofersen , sold under the brand name Qalsody , is a medication used for the treatment of amyotrophic lateral sclerosis (ALS). [ 3 ] Tofersen is an antisense oligonucleotide that targets the production of superoxide dismutase 1 , an enzyme whose mutant form is commonly associated with amyotrophic lateral sclerosis. It is administered as an intrathecal injection. [ 3 ]
The most common side effects include fatigue, arthralgia (joint pain), increased cerebrospinal (brain and spinal cord) fluid white blood cells, and myalgia (muscle pain). [ 3 ]
Tofersen was approved for medical use in the United States in April 2023, [ 3 ] [ 6 ] and in the European Union in May 2024. [ 4 ] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication . [ 7 ]
Tofersen is indicated to treat people with amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene (SOD1-ALS). [ 3 ]
Tofersen was developed by Ionis Pharmaceuticals and was licensed to, and co-developed by, Biogen . [ 8 ] [ 9 ]
The effectiveness of tofersen was evaluated in a 28-week, randomized, double-blind, placebo-controlled clinical study in 147 participants with weakness attributable to amyotrophic lateral sclerosis and a superoxide dismutase 1 (SOD-1) mutation confirmed by a central laboratory. [ 3 ] The study randomly assigned 108 participants in a 2:1 ratio to receive treatment with either tofersen 100 mg (n = 72) or placebo (n = 36) for 24 weeks (three loading doses followed by five maintenance doses). [ 3 ] The participants were approximately 43% female; 57% male; 64% White; and 8% Asian. [ 3 ] The average age was 49.8 years (range from 23 to 78 years). [ 3 ]
The stage III clinical trial was conducted by the Neuroscience Institute and Sheffield Institute for Translational Neuroscience (SITraN), both at the University of Sheffield. [ 10 ]
The US Food and Drug Administration (FDA) granted the application for tofersen priority review , orphan drug , and fast track designations. [ 3 ] [ 7 ]
Only around 1-2% of ALS cases diagnosed in the United States each year carry the specific SOD1 mutation targeted by the drug. [ 11 ] Fewer than 500 patients a year are expected to be eligible for the drug, which is expected to cost over $100,000 for a year's treatment. [ 3 ] [ 12 ] [ 13 ] [ 14 ]
In February 2024, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization under exceptional circumstances for the medicinal product Qalsody, intended for the treatment of a type of amyotrophic lateral sclerosis caused by a defective superoxide dismutase 1 (SOD1) protein. [ 4 ] [ 15 ] The applicant for this medicinal product is Biogen Netherlands B.V. [ 4 ] Tofersen was approved for medical use in the European Union in May 2024. [ 5 ] | https://en.wikipedia.org/wiki/Tofersen |
" Tofu-dreg project " ( Chinese : 豆腐渣工程 ) is a phrase used in the Chinese-speaking world to describe a very poorly constructed building, sometimes called just " Tofu buildings ". The phrase was coined by Zhu Rongji , the former premier of the People's Republic of China , on a 1998 visit to Jiujiang City , Jiangxi Province to describe poorly built levees in the Yangtze River . [ 1 ] The phrase is notably used referring to buildings that collapsed in the 2008 Sichuan earthquake disaster, [ 2 ] [ 3 ] [ 4 ] [ 5 ] [ 6 ] [ 7 ] and the Bangkok Audit Office skyscraper collapse initiated by aftershocks from the March 2025 Myanmar earthquake over 1000km away, which was constructed with poor construction techniques and materials. [ 8 ] [ 9 ]
In China, the term tofu dregs (the pieces left over after making tofu) is widely used as a metaphor for shoddy work, hence the implication that a "tofu-dreg project" is a poorly executed project. [ 8 ] [ 9 ]
According to Chinese architect Li Hu , tofu-dreg projects in China are vastly outnumbered by buildings without construction flaws. Li said that in most cases, ill-constructed buildings do not collapse but merely have a reduced lifespan or leakages. [ 10 ]
During the 2008 Sichuan earthquake , many schoolhouses collapsed; resulting in the death of students. These buildings have been used to exemplify tofu-dreg projects. The collapses were linked to allegations of corruption in the construction of Chinese schools .
…School construction is the worst. First, there's not enough capital. Schools in poor areas have small budgets and, unlike schools in the cities, they can't collect huge fees, so they're pressed for money. With construction, add in exploitation by government officials, education officials, school managers, etc. and you can imagine what's left over for the actual building of schools. When earthquake prevention standards are raised, government departments, major businesses, etc. will all appraise and reinforce their buildings. But these schools with their 70s-era buildings, no one pays attention to them. Because of this, the older school buildings are suffer[ing] from inadequate protection while the new buildings have been shoddily constructed.
On May 15, 2008, Geoffrey York of The Globe and Mail reported that the shoddily constructed buildings are commonly called "tofu buildings" because builders cut corners by replacing steel rods with thin iron wires for concrete reinforcement; using inferior grade cement, if any at all; and using fewer bricks than they should. One local was quoted in the article as saying that "the supervising agencies did not check to see if it met the national standards." [ 12 ]
The state-controlled media has largely ignored the tofu-dregs schoolhouses, under directives from the propaganda bureau's instructions. Parents, volunteers, and journalists who have questioned authorities have been intimidated or arrested. [ 13 ] [ 14 ] [ 15 ] [ 16 ] To quash the issue, riot police officers have broken up protests by parents, cordons have been set up around the schools in question, and reportage simply stopped. [ 17 ] | https://en.wikipedia.org/wiki/Tofu-dreg_project |
The tog is a measure of thermal insulance of a unit area, also known as thermal resistance . It is commonly used in the textile industry and often seen quoted on household items such as duvets , sleeping bags and carpet underlay .
F. T. Peirce and W. H. Rees, of the Shirley Institute in Manchester , England, developed the tog in 1946 as more convenient alternative to the SI unit of m 2 ⋅K/W, writing in their paper The Transmission of Heat Through Textile Fabrics – part II : [ 1 ]
The results given in this paper are expressed in terms of watts, °C and metres. So that practical clothing may be described conveniently by a range of small integers, the unit of thermal resistance, to be called the “tog”, is the resistance that will maintain a temperature difference of 0.1°C. with a flux of 1 watt per square metre, or in more practical terms, 10°C. with a flux of 1 watt per square decimetre.
Peirce and Rees do not give any explanation in their paper for their choice of the term "tog", nor its derivation. They do, however, refer to an earlier proposed unit, the "clo", coined by Gagge et al in their 1941 paper A Practical System of Units for the Description of the Heat Exchange of Man with his Environment [ 2 ] , writing "The conditions used to define the clo are unsatisfactory even for comparative physiological experiments." [ 1 ] It is possible that Peirce and Rees chose "tog" as a three-letter term, mirroring "clo", based on the informal word "togs" meaning "clothing", which according to the Oxford English Dictionary is a contraction of the 19th century thieves' cant word togeman , cognate with toga , meaning "cloak or loose coat". [ 3 ]
The Oxford English Dictionary gives no etymology for "tog" other than its definition by Peirce and Rees. [ 4 ] According to Collins Dictionary , the unit "tog" is derived from "tog" meaning clothes. [ 5 ] Chambers Dictionary states "Etymology : 1940s: perhaps from tog [as clothing]". [ 6 ]
The backronym thermal overall grade is in common commercial use.
The basic unit of insulation coefficient is the R SI , (1 m 2 ⋅K/W). 1 tog = 0.1 R SI . There is also a US clothing unit, the clo , equivalent to 0.155 R SI or 1.55 tog, described in ASTM D-1518. [ 7 ]
A tog is 0.1⋅m 2 ⋅K/W. In other words, the thermal resistance in togs is equal to ten times the temperature difference (in °C ) between the two surfaces of a material, when the flow of heat is equal to one watt per square metre. [ 1 ]
British duvets are sold in steps of 1.5 tog from 3.0 tog (summer) to 16.5 tog (extra-warm). The stated values are a minimum; actual values may be up to 3 tog higher. Also, these values assume there is no added duvet cover that can trap air.
Some manufacturers have marketed combined duvet sets consisting of two duvets: one of approximately 4.5 tog and one of approximately 9.0 tog. These can be used individually as summer (4.5 tog) and spring/autumn (9.0 tog). When joined together using press studs around the edges, or Velcro strips across each of the corners, they become a 13.5 tog winter duvet and as such can be made to suit all seasons.
Launched in the 1940s by the Shirley Institute, the Shirley Togmeter is the standard apparatus for rating thermal resistance of textiles, commonly known as the Tog Test. This apparatus, described in BS 4745:2005 [ 8 ] measures a sample of textile, either between two metal plates (for underclothing) or between a metal plate and free air (for outer layers). Each industry has its own specifications and methods for measuring thermal properties. | https://en.wikipedia.org/wiki/Tog_(unit) |
Together for Sustainability AISBL (TfS) [ 1 ] is a joint initiative of chemical companies, founded in 2011. It focuses on the promotion of sustainability practices in the chemical industry's supply chain , currently gathering chemical companies around a single standard of auditing and assessment.
Over the past few years sustainability aspects in the chemical industry have become more important and holistic. Nowadays, chemical companies' measures focusing sustainability include apart from ecological aspects also social concerns and collaborative issues.
Today, it has been well accepted that the creation of sustainable chemical supply chains requires a joint effort beyond individual businesses. These efforts should integrate chemical companies, suppliers, customers as well as consumers. [ 2 ]
Prof. Dr Wolfgang Stolze and Marc Müller of the University of St. Gallen summarize the development in the chemical industry in recent years as follows: "The scope of sustainability in the chemical industry has evolved from a firm-level construct with a strong focus on green aspects to a chain-level approach attempting to address the triple bottom line of economic, social and environmental elements." [ 3 ]
The Together for Sustainability initiative was founded in 2011 by BASF , Bayer , Evonik , Henkel , Lanxess , and Solvay . The objective was to develop a global supplier engagement program and improve their own sustainability sourcing practices in line with the United Nations Global Compact . Since January 2015, the TfS initiative is incorporated as an international non-profit association according to the Belgian law.
Since June 2012, TfS conducts assessments and audits by independent experts, as well as the early partnership with the French company EcoVadis, which provided with sustainability scorecards and benchmarks. [ 4 ]
In June 2023, Jennifer Jewson, CPO of LyondellBasell , was elected as president of the TfS. [ 5 ]
The TfS is governed by two main organs, the General Assembly and the Steering Committee.
The General Assembly is formed by all the Chief Procurement Officers of the member companies, and holds power over the direction and structure of the organization, as well as approving the decisions of the Steering Committee.
The Steering Committee, formed by six elected members of the General Assembly as well as the TfS president, is the executive council of the organization and decides upon its activities and projects.
Additionally, TfS has several Regional Operating Committees (Asia, North America and South America) as well as, currently, five mission-specific work streams led and staffed by participants from the TfS member companies:
TfS' headquarter is in Brussels . It manages the day-to-day affairs of the organization and stays in close contact with the representatives and coordinators of the member companies.
TfS has a partnership with several other chemical industry associations: American Chemistry Council (ACC) , European Chemical Industry Council (CEFIC) , German Chemistry Council (VCI) , China Petroleum and Chemical Industry Federation (CPCIF) , Indian Chemical Council (ICC) , [ 6 ] and the Associação Brasileira da Indústria Química (ABIQUIM) .
TfS Membership is open to all companies in the chemical industry who subscribe to the United Nations Global Compact , Responsible Care , and show a commitment to sustainability. TfS membership has been growing steadily since its founding, and in April 2022 its members have a joint global turnover of over €500 billion. [ 7 ]
As of February 2025, TfS has 55 member companies. | https://en.wikipedia.org/wiki/Together_for_Sustainability |
Concrete is a composite material composed of aggregate bound together with a fluid cement that cures to a solid over time. It is the second-most-used substance (after water ), [ 1 ] the most–widely used building material, [ 2 ] and the most-manufactured material in the world. [ 3 ]
When aggregate is mixed with dry Portland cement and water , the mixture forms a fluid slurry that can be poured and molded into shape. The cement reacts with the water through a process called hydration, [ 4 ] which hardens it after several hours to form a solid matrix that binds the materials together into a durable stone-like material with various uses. [ 5 ] This time allows concrete to not only be cast in forms, but also to have a variety of tooled processes performed. The hydration process is exothermic , which means that ambient temperature plays a significant role in how long it takes concrete to set. Often, additives (such as pozzolans or superplasticizers ) are included in the mixture to improve the physical properties of the wet mix, delay or accelerate the curing time, or otherwise modify the finished material. Most structural concrete is poured with reinforcing materials (such as steel rebar ) embedded to provide tensile strength , yielding reinforced concrete .
Before the invention of Portland cement in the early 1800s, lime -based cement binders, such as lime putty, were often used. The overwhelming majority of concretes are produced using Portland cement, but sometimes with other hydraulic cements , such as calcium aluminate cement . [ 6 ] [ 7 ] Many other non-cementitious types of concrete exist with other methods of binding aggregate together, including asphalt concrete with a bitumen binder, which is frequently used for road surfaces , and polymer concretes that use polymers as a binder.
Concrete is distinct from mortar . [ 8 ] Whereas concrete is itself a building material, and contains both coarse (large) and fine (small) aggregate particles, mortar contains only fine aggregates and is mainly used as a bonding agent to hold bricks , tiles and other masonry units together. [ 9 ] Grout is another material associated with concrete and cement. It also does not contain coarse aggregates and is usually either pourable or thixotropic , and is used to fill gaps between masonry components or coarse aggregate which has already been put in place. Some methods of concrete manufacture and repair involve pumping grout into the gaps to make up a solid mass in situ .
The word concrete comes from the Latin word " concretus " (meaning compact or condensed), [ 10 ] the perfect passive participle of " concrescere ", from " con -" (together) and " crescere " (to grow).
Concrete floors were found in the royal palace of Tiryns , Greece, which dates roughly to 1400 to 1200 BC. [ 11 ] [ 12 ] Lime mortars were used in Greece, such as in Crete and Cyprus, in 800 BC. The Assyrian Jerwan Aqueduct (688 BC) made use of waterproof concrete . [ 13 ] Concrete was used for construction in many ancient structures. [ 14 ]
Mayan concrete at the ruins of Uxmal (AD 850–925) is referenced in Incidents of Travel in the Yucatán by John L. Stephens . "The roof is flat and had been covered with cement". "The floors were cement, in some places hard, but, by long exposure, broken, and now crumbling under the feet." "But throughout the wall was solid, and consisting of large stones imbedded in mortar, almost as hard as rock."
Small-scale production of concrete-like materials was pioneered by the Nabatean traders who occupied and controlled a series of oases and developed a small empire in the regions of southern Syria and northern Jordan from the 4th century BC. They discovered the advantages of hydraulic lime , with some self-cementing properties, by 700 BC. They built kilns to supply mortar for the construction of rubble masonry houses, concrete floors, and underground waterproof cisterns . They kept the cisterns secret as these enabled the Nabataeans to thrive in the desert. [ 15 ] Some of these structures survive to this day. [ 15 ]
In the Ancient Egyptian and later Roman eras, builders discovered that adding volcanic ash to lime allowed the mix to set underwater. They discovered the pozzolanic reaction . [ 16 ]
The Romans used concrete extensively from 300 BC to AD 476. [ 18 ] During the Roman Empire, Roman concrete (or opus caementicium ) was made from quicklime , pozzolana and an aggregate of pumice . [ 19 ] Its widespread use in many Roman structures , a key event in the history of architecture termed the Roman architectural revolution , freed Roman construction from the restrictions of stone and brick materials. It enabled revolutionary new designs in terms of both structural complexity and dimension. [ 20 ] The Colosseum in Rome was built largely of concrete, and the Pantheon has the world's largest unreinforced concrete dome. [ 21 ]
Concrete, as the Romans knew it, was a new and revolutionary material. Laid in the shape of arches , vaults and domes , it quickly hardened into a rigid mass, free from many of the internal thrusts and strains that troubled the builders of similar structures in stone or brick. [ 22 ]
Modern tests show that opus caementicium had a similar compressive strength to modern Portland-cement concrete (c. 200 kg/cm 2 [20 MPa; 2,800 psi]). [ 23 ] However, due to the absence of reinforcement, its tensile strength was far lower than modern reinforced concrete , and its mode of application also differed: [ 24 ]
Modern structural concrete differs from Roman concrete in two important details. First, its mix consistency is fluid and homogeneous, allowing it to be poured into forms rather than requiring hand-layering together with the placement of aggregate, which, in Roman practice, often consisted of rubble . Second, integral reinforcing steel gives modern concrete assemblies great strength in tension, whereas Roman concrete could depend only upon the strength of the concrete bonding to resist tension. [ 25 ]
The long-term durability of Roman concrete structures was found to be due to the presence of pyroclastic (volcanic) rock and ash in the concrete mix. The crystallization of strätlingite (a complex calcium aluminosilicate hydrate) [ 26 ] during the formation of the concrete and its merging with similar calcium–aluminium-silicate–hydrate structures helped give the Roman concrete a greater degree of fracture resistance compared to modern concrete. [ 27 ] In addition, Roman concrete is significantly more resistant to erosion by seawater than modern concrete; the aforementioned pyroclastic materials react with seawater to form Al- tobermorite crystals over time. [ 28 ] [ 29 ] The use of hot mixing in preparation of concrete, leading to the formation of lime clasts in the final product, has been proposed to give the Roman concrete a self-healing ability . [ 30 ] [ 31 ]
The widespread use of concrete in many Roman structures ensured that many survive to the present day. The Baths of Caracalla in Rome are just one example. Many Roman aqueducts and bridges, such as the magnificent Pont du Gard in southern France, have masonry cladding on a concrete core, as does the dome of the Pantheon .
After the Roman Empire, the use of burned lime and pozzolana was greatly reduced. Low kiln temperatures in the burning of lime, lack of pozzolana, and poor mixing all contributed to a decline in the quality of concrete and mortar. From the 11th century, the increased use of stone in church and castle construction led to an increased demand for mortar. Quality began to improve in the 12th century through better grinding and sieving. Medieval lime mortars and concretes were non-hydraulic and were used for binding masonry, "hearting" (binding rubble masonry cores) and foundations. Bartholomaeus Anglicus in his De proprietatibus rerum (1240) describes the making of mortar. In an English translation from 1397, it reads "lyme ... is a stone brent; by medlynge thereof with sonde and water sement is made". From the 14th century, the quality of mortar was again excellent, but only from the 17th century was pozzolana commonly added. [ 32 ]
The Canal du Midi was built using concrete in 1670. [ 33 ]
Perhaps the greatest step forward in the modern use of concrete was Smeaton's Tower , built by British engineer John Smeaton in Devon , England, between 1756 and 1759. This third Eddystone Lighthouse pioneered the use of hydraulic lime in concrete, using pebbles and powdered brick as aggregate. [ 34 ]
A method for producing Portland cement was developed in England and patented by Joseph Aspdin in 1824. [ 35 ] Aspdin chose the name for its similarity to Portland stone , which was quarried on the Isle of Portland in Dorset , England. His son William continued developments into the 1840s, earning him recognition for the development of "modern" Portland cement. [ 36 ]
Reinforced concrete was invented in 1849 by Joseph Monier . [ 37 ] and the first reinforced concrete house was built by François Coignet [ 38 ] in 1853.
The first concrete reinforced bridge was designed and built by Joseph Monier in 1875. [ 39 ]
Prestressed concrete and post-tensioned concrete were pioneered by Eugène Freyssinet , a French structural and civil engineer . Concrete components or structures are compressed by tendon cables during, or after, their fabrication in order to strengthen them against tensile forces developing when put in service. Freyssinet patented the technique on 2 October 1928. [ 40 ]
Concrete is an artificial composite material , comprising a matrix of cementitious binder (typically Portland cement paste or asphalt ) and a dispersed phase or "filler" of aggregate (typically a rocky material, loose stones, and sand). The binder "glues" the filler together to form a synthetic conglomerate . [ 41 ] Many types of concrete are available, determined by the formulations of binders and the types of aggregate used to suit the application of the engineered material. These variables determine strength and density, as well as chemical and thermal resistance of the finished product.
Construction aggregates consist of large chunks of material in a concrete mix, generally a coarse gravel or crushed rocks such as limestone , or granite , along with finer materials such as sand .
Cement paste, most commonly made of Portland cement , is the most prevalent kind of concrete binder. For cementitious binders, water is mixed with the dry cement powder and aggregate, which produces a semi-liquid slurry (paste) that can be shaped, typically by pouring it into a form. The concrete solidifies and hardens through a chemical process called hydration . The water reacts with the cement, which bonds the other components together, creating a robust, stone-like material. Other cementitious materials, such as fly ash and slag cement , are sometimes added—either pre-blended with the cement or directly as a concrete component—and become a part of the binder for the aggregate. [ 42 ] Fly ash and slag can enhance some properties of concrete such as fresh properties and durability. [ 42 ] Alternatively, other materials can also be used as a concrete binder: the most prevalent substitute is asphalt , which is used as the binder in asphalt concrete .
Admixtures are added to modify the cure rate or properties of the material. Mineral admixtures use recycled materials as concrete ingredients. Conspicuous materials include fly ash , a by-product of coal-fired power plants ; ground granulated blast furnace slag , a by-product of steelmaking ; and silica fume , a by-product of industrial electric arc furnaces .
Structures employing Portland cement concrete usually include steel reinforcement because this type of concrete can be formulated with high compressive strength , but always has lower tensile strength . Therefore, it is usually reinforced with materials that are strong in tension, typically steel rebar .
The mix design depends on the type of structure being built, how the concrete is mixed and delivered, and how it is placed to form the structure.
Portland cement is the most common type of cement in general usage. It is a basic ingredient of concrete, mortar , and many plasters . [ 43 ] It consists of a mixture of calcium silicates ( alite , belite ), aluminates and ferrites —compounds, which will react with water. Portland cement and similar materials are made by heating limestone (a source of calcium) with clay or shale (a source of silicon, aluminium and iron) and grinding this product (called clinker ) with a source of sulfate (most commonly gypsum ).
Cement kilns are extremely large, complex, and inherently dusty industrial installations. Of the various ingredients used to produce a given quantity of concrete, the cement is the most energetically expensive. Even complex and efficient kilns require 3.3 to 3.6 gigajoules of energy to produce a ton of clinker and then grind it into cement . Many kilns can be fueled with difficult-to-dispose-of wastes, the most common being used tires. The extremely high temperatures and long periods of time at those temperatures allows cement kilns to efficiently and completely burn even difficult-to-use fuels. [ 44 ] The five major compounds of calcium silicates and aluminates comprising Portland cement range from 5 to 50% in weight.
Combining water with a cementitious material forms a cement paste by the process of hydration. The cement paste glues the aggregate together, fills voids within it, and makes it flow more freely. [ 45 ]
As stated by Abrams' law , a lower water-to-cement ratio yields a stronger, more durable concrete, whereas more water gives a freer-flowing concrete with a higher slump . [ 46 ] The hydration of cement involves many concurrent reactions. The process involves polymerization , the interlinking of the silicates and aluminate components as well as their bonding to sand and gravel particles to form a solid mass. [ 47 ] One illustrative conversion is the hydration of tricalcium silicate:
The hydration (curing) of cement is irreversible. [ 48 ]
Fine and coarse aggregates make up the bulk of a concrete mixture. Sand , natural gravel, and crushed stone are used mainly for this purpose. Recycled aggregates (from construction, demolition, and excavation waste) are increasingly used as partial replacements for natural aggregates, while a number of manufactured aggregates, including air-cooled blast furnace slag and bottom ash are also permitted.
The size distribution of the aggregate determines how much binder is required. Aggregate with a very even size distribution has the biggest gaps whereas adding aggregate with smaller particles tends to fill these gaps. The binder must fill the gaps between the aggregate as well as paste the surfaces of the aggregate together, and is typically the most expensive component. Thus, variation in sizes of the aggregate reduces the cost of concrete. [ 49 ] The aggregate is nearly always stronger than the binder, so its use does not negatively affect the strength of the concrete.
Redistribution of aggregates after compaction often creates non-homogeneity due to the influence of vibration. This can lead to strength gradients. [ 50 ]
Decorative stones such as quartzite , small river stones or crushed glass are sometimes added to the surface of concrete for a decorative "exposed aggregate" finish, popular among landscape designers.
Admixtures are materials in the form of powder or fluids that are added to the concrete to give it certain characteristics not obtainable with plain concrete mixes. Admixtures are defined as additions "made as the concrete mix is being prepared". [ 51 ] The most common admixtures are retarders and accelerators. In normal use, admixture dosages are less than 5% by mass of cement and are added to the concrete at the time of batching/mixing. [ 52 ] (See § Production below.) The common types of admixtures [ 53 ] are as follows:
Inorganic materials that have pozzolanic or latent hydraulic properties, these very fine-grained materials are added to the concrete mix to improve the properties of concrete (mineral admixtures), [ 52 ] or as a replacement for Portland cement (blended cements). [ 59 ] Products which incorporate limestone , fly ash , blast furnace slag , and other useful materials with pozzolanic properties into the mix, are being tested and used. These developments are ever growing in relevance to minimize the impacts caused by cement use, notorious for being one of the largest producers (at about 5 to 10%) of global greenhouse gas emissions . [ 60 ] The use of alternative materials also is capable of lowering costs, improving concrete properties, and recycling wastes, the latest being relevant for circular economy aspects of the construction industry , whose demand is ever growing with greater impacts on raw material extraction, waste generation and landfill practices.
Concrete production is the process of mixing together the various ingredients—water, aggregate, cement, and any additives—to produce concrete. Concrete production is time-sensitive. Once the ingredients are mixed, workers must put the concrete in place before it hardens. In modern usage, most concrete production takes place in a large type of industrial facility called a concrete plant , or often a batch plant. The usual method of placement is casting in formwork , which holds the mix in shape until it has set enough to hold its shape unaided.
Concrete plants come in two main types, ready-mix plants and central mix plants. A ready-mix plant blends all of the solid ingredients, while a central mix does the same but adds water. A central-mix plant offers more precise control of the concrete quality. Central mix plants must be close to the work site where the concrete will be used, since hydration begins at the plant.
A concrete plant consists of large hoppers for storage of various ingredients like cement, storage for bulk ingredients like aggregate and water, mechanisms for the addition of various additives and amendments, machinery to accurately weigh, move, and mix some or all of those ingredients, and facilities to dispense the mixed concrete, often to a concrete mixer truck.
Modern concrete is usually prepared as a viscous fluid, so that it may be poured into forms. The forms are containers that define the desired shape. Concrete formwork can be prepared in several ways, such as slip forming and steel plate construction . Alternatively, concrete can be mixed into dryer, non-fluid forms and used in factory settings to manufacture precast concrete products.
Interruption in pouring the concrete can cause the initially placed material to begin to set before the next batch is added on top. This creates a horizontal plane of weakness called a cold joint between the two batches. [ 67 ] Once the mix is where it should be, the curing process must be controlled to ensure that the concrete attains the desired attributes. During concrete preparation, various technical details may affect the quality and nature of the product.
Design mix ratios are decided by an engineer after analyzing the properties of the specific ingredients being used. Instead of using a 'nominal mix' of 1 part cement, 2 parts sand, and 4 parts aggregate, a civil engineer will custom-design a concrete mix to exactly meet the requirements of the site and conditions, setting material ratios and often designing an admixture package to fine-tune the properties or increase the performance envelope of the mix. Design-mix concrete can have very broad specifications that cannot be met with more basic nominal mixes, but the involvement of the engineer often increases the cost of the concrete mix.
Concrete mixes are primarily divided into nominal mix, standard mix and design mix.
Nominal mix ratios are given in volume of Cement : Sand : Aggregate {\displaystyle {\text{Cement : Sand : Aggregate}}} . Nominal mixes are a simple, fast way of getting a basic idea of the properties of the finished concrete without having to perform testing in advance.
Various governing bodies (such as British Standards ) define nominal mix ratios into a number of grades, usually ranging from lower compressive strength to higher compressive strength. The grades usually indicate the 28-day cure strength. [ 68 ]
Thorough mixing is essential to produce uniform, high-quality concrete.
Separate paste mixing has shown that the mixing of cement and water into a paste before combining these materials with aggregates can increase the compressive strength of the resulting concrete. [ 69 ] The paste is generally mixed in a high-speed , shear-type mixer at a w/c (water to cement ratio) of 0.30 to 0.45 by mass. The cement paste premix may include admixtures such as accelerators or retarders, superplasticizers , pigments , or silica fume . The premixed paste is then blended with aggregates and any remaining batch water and final mixing is completed in conventional concrete mixing equipment. [ 70 ]
Resonant acoustic mixing has also been found effective in producing ultra-high performance cementitious materials, as it produces a dense matrix with low porosity. [ 71 ]
Workability is the ability of a fresh (plastic) concrete mix to fill the form/mold properly with the desired work (pouring, pumping, spreading, tamping, vibration) and without reducing the concrete's quality. Workability depends on water content, aggregate (shape and size distribution), cementitious content and age (level of hydration ) and can be modified by adding chemical admixtures, like superplasticizer. Raising the water content or adding chemical admixtures increases concrete workability. Excessive water leads to increased bleeding or segregation of aggregates (when the cement and aggregates start to separate), with the resulting concrete having reduced quality. Changes in gradation can also affect workability of the concrete, although a wide range of gradation can be used for various applications. [ 72 ] [ 73 ] An undesirable gradation can mean using a large aggregate that is too large for the size of the formwork, or which has too few smaller aggregate grades to serve to fill the gaps between the larger grades, or using too little or too much sand for the same reason, or using too little water, or too much cement, or even using jagged crushed stone instead of smoother round aggregate such as pebbles. Any combination of these factors and others may result in a mix which is too harsh, i.e., which does not flow or spread out smoothly, is difficult to get into the formwork, and which is difficult to surface finish. [ 74 ]
Workability can be measured by the concrete slump test , a simple measure of the plasticity of a fresh batch of concrete following the ASTM C 143 or EN 12350-2 test standards. Slump is normally measured by filling an " Abrams cone " with a sample from a fresh batch of concrete. The cone is placed with the wide end down onto a level, non-absorptive surface. It is then filled in three layers of equal volume, with each layer being tamped with a steel rod to consolidate the layer. When the cone is carefully lifted off, the enclosed material slumps a certain amount, owing to gravity. A relatively dry sample slumps very little, having a slump value of one or two inches (25 or 50 mm) out of one foot (300 mm). A relatively wet concrete sample may slump as much as eight inches. Workability can also be measured by the flow table test .
Slump can be increased by addition of chemical admixtures such as plasticizer or superplasticizer without changing the water-cement ratio . [ 75 ] Some other admixtures, especially air-entraining admixture, can increase the slump of a mix.
High-flow concrete, like self-consolidating concrete , is tested by other flow-measuring methods. One of these methods includes placing the cone on the narrow end and observing how the mix flows through the cone while it is gradually lifted.
After mixing, concrete is a fluid and can be pumped to the location where needed.
Concrete must be kept moist during curing in order to achieve optimal strength and durability . [ 76 ] During curing hydration occurs, allowing calcium-silicate hydrate (C-S-H) to form. Over 90% of a mix's final strength is typically reached within four weeks, with the remaining 10% achieved over years or even decades. [ 77 ] The conversion of calcium hydroxide in the concrete into calcium carbonate from absorption of CO 2 over several decades further strengthens the concrete and makes it more resistant to damage. This carbonation reaction, however, lowers the pH of the cement pore solution and can corrode the reinforcement bars.
Hydration and hardening of concrete during the first three days is critical. Abnormally fast drying and shrinkage due to factors such as evaporation from wind during placement may lead to increased tensile stresses at a time when it has not yet gained sufficient strength, resulting in greater shrinkage cracking. The early strength of the concrete can be increased if it is kept damp during the curing process. Minimizing stress prior to curing minimizes cracking. High-early-strength concrete is designed to hydrate faster, often by increased use of cement that increases shrinkage and cracking. The strength of concrete changes (increases) for up to three years. It depends on cross-section dimension of elements and conditions of structure exploitation. [ 50 ] Addition of short-cut polymer fibers can improve (reduce) shrinkage-induced stresses during curing and increase early and ultimate compression strength. [ 78 ]
Properly curing concrete leads to increased strength and lower permeability and avoids cracking where the surface dries out prematurely. Care must also be taken to avoid freezing or overheating due to the exothermic setting of cement. Improper curing can cause spalling , reduced strength, poor abrasion resistance and cracking .
During the curing period, concrete is ideally maintained at controlled temperature and humidity. To ensure full hydration during curing, concrete slabs are often sprayed with "curing compounds" that create a water-retaining film over the concrete. Typical films are made of wax or related hydrophobic compounds. After the concrete is sufficiently cured, the film is allowed to abrade from the concrete through normal use. [ 79 ]
Traditional conditions for curing involve spraying or ponding the concrete surface with water. The adjacent picture shows one of many ways to achieve this, ponding—submerging setting concrete in water and wrapping in plastic to prevent dehydration. Additional common curing methods include wet burlap and plastic sheeting covering the fresh concrete.
For higher-strength applications, accelerated curing techniques may be applied to the concrete. A common technique involves heating the poured concrete with steam, which serves to both keep it damp and raise the temperature so that the hydration process proceeds more quickly and more thoroughly.
Asphalt concrete (commonly called asphalt , [ 80 ] blacktop , or pavement in North America, and tarmac , bitumen macadam , or rolled asphalt in the United Kingdom and Ireland ) is a composite material commonly used to surface roads , parking lots , airports , as well as the core of embankment dams . [ 81 ] Asphalt mixtures have been used in pavement construction since the beginning of the twentieth century. [ 82 ] It consists of mineral aggregate bound together with asphalt , laid in layers, and compacted. The process was refined and enhanced by Belgian inventor and U.S. immigrant Edward De Smedt . [ 83 ]
The terms asphalt (or asphaltic ) concrete , bituminous asphalt concrete , and bituminous mixture are typically used only in engineering and construction documents, which define concrete as any composite material composed of mineral aggregate adhered with a binder. The abbreviation, AC , is sometimes used for asphalt concrete but can also denote asphalt content or asphalt cement , referring to the liquid asphalt portion of the composite material.
Graphene enhanced concretes are standard designs of concrete mixes, except that during the cement-mixing or production process, a small amount of chemically engineered graphene (typically < 0.5% by weight) is added. [ 84 ] [ 85 ] These enhanced graphene concretes are designed around the concrete application.
Bacteria such as Bacillus pasteurii , Bacillus pseudofirmus , Bacillus cohnii , Sporosarcina pasteuri , and Arthrobacter crystallopoietes increase the compression strength of concrete through their biomass. However some forms of bacteria can also be concrete-destroying. [ 86 ] Bacillus sp. CT-5. can reduce corrosion of reinforcement in reinforced concrete by up to four times. Sporosarcina pasteurii reduces water and chloride permeability. B. pasteurii increases resistance to acid. [ 87 ] Bacillus pasteurii and B. sphaericuscan induce calcium carbonate precipitation in the surface of cracks, adding compression strength. [ 88 ]
Nanoconcrete (also spelled "nano concrete"' or "nano-concrete") is a class of materials that contains Portland cement particles that are no greater than 100 μm [ 89 ] and particles of silica no greater than 500 μm, which fill voids that would otherwise occur in normal concrete, thereby substantially increasing the material's strength. [ 90 ] It is widely used in foot and highway bridges where high flexural and compressive strength are indicated. [ 88 ]
Pervious concrete is a mix of specially graded coarse aggregate, cement, water, and little-to-no fine aggregates. This concrete is also known as "no-fines" or porous concrete. Mixing the ingredients in a carefully controlled process creates a paste that coats and bonds the aggregate particles. The hardened concrete contains interconnected air voids totaling approximately 15 to 25 percent. Water runs through the voids in the pavement to the soil underneath. Air entrainment admixtures are often used in freeze-thaw climates to minimize the possibility of frost damage. Pervious concrete also permits rainwater to filter through roads and parking lots, to recharge aquifers, instead of contributing to runoff and flooding. [ 91 ]
Polymer concretes are mixtures of aggregate and any of various polymers and may be reinforced. The cement is costlier than lime-based cements, but polymer concretes nevertheless have advantages; they have significant tensile strength even without reinforcement, and they are largely impervious to water. Polymer concretes are frequently used for the repair and construction of other applications, such as drains.
Plant fibers and particles can be used in a concrete mix or as a reinforcement. [ 92 ] [ 93 ] [ 94 ] These materials can increase ductility but the lignocellulosic particles hydrolyze during concrete curing as a result of alkaline environment and elevated temperatures [ 95 ] [ 96 ] [ 97 ] Such process, that is difficult to measure, [ 98 ] can affect the properties of the resulting concrete.
Sulfur concrete is a special concrete that uses sulfur as a binder and does not require cement or water.
Volcanic concrete substitutes volcanic rock for the limestone that is burned to form clinker. It consumes a similar amount of energy, but does not directly emit carbon as a byproduct. [ 99 ] Volcanic rock/ash are used as supplementary cementitious materials in concrete to improve the resistance to sulfate, chloride and alkali silica reaction due to pore refinement. [ 100 ] Also, they are generally cost effective in comparison to other aggregates, [ 101 ] good for semi and light weight concretes, [ 101 ] and good for thermal and acoustic insulation. [ 101 ]
Pyroclastic materials, such as pumice, scoria, and ashes are formed from cooling magma during explosive volcanic eruptions. They are used as supplementary cementitious materials (SCM) or as aggregates for cements and concretes. [ 102 ] They have been extensively used since ancient times to produce materials for building applications. For example, pumice and other volcanic glasses were added as a natural pozzolanic material for mortars and plasters during the construction of the Villa San Marco in the Roman period (89 BC – 79 AD), which remain one of the best-preserved otium villae of the Bay of Naples in Italy. [ 103 ]
Waste light is a form of polymer modified concrete. The specific polymer admixture allows the replacement of all the traditional aggregates (gravel, sand, stone) by any mixture of solid waste materials in the grain size of 3–10 mm to form a low-compressive-strength (3–20 N/mm 2 ) product [ 104 ] for road and building construction. One cubic meter of waste light concrete contains 1.1–1.3 m 3 of shredded waste and no other aggregates.
Recycled aggregate concretes are standard concrete mixes with the addition or substitution of natural aggregates with recycled aggregates sourced from construction and demolition wastes, disused pre-cast concretes or masonry. In most cases, recycled aggregate concrete results in higher water absorption levels by capillary action and permeation, which are the prominent determiners of the strength and durability of the resulting concrete. The increase in water absorption levels is mainly caused by the porous adhered mortar that exists in the recycled aggregates. Accordingly, recycled concrete aggregates that have been washed to reduce the quantity of mortar adhered to aggregates show lower water absorption levels compared to untreated recycled aggregates.
The quality of the recycled aggregate concrete is determined by several factors, including the size, the number of replacement cycles, and the moisture levels of the recycled aggregates. When the recycled concrete aggregates are crushed into coarser fractures, the mixed concrete shows better permeability levels, resulting in an overall increase in strength. In contrast, recycled masonry aggregates provide better qualities when crushed in finer fractures. With each generation of recycled concrete, the resulting compressive strength decreases.
Concrete has relatively high compressive strength , but much lower tensile strength . [ 105 ] Therefore, it is usually reinforced with materials that are strong in tension (often steel). The elasticity of concrete is relatively constant at low stress levels but starts decreasing at higher stress levels as matrix cracking develops. Concrete has a very low coefficient of thermal expansion and shrinks as it matures. All concrete structures crack to some extent, due to shrinkage and tension. Concrete that is subjected to long-duration forces is prone to creep .
Tests can be performed to ensure that the properties of concrete correspond to specifications for the application.
The ingredients affect the strengths of the material. Concrete strength values are usually specified as the lower-bound compressive strength of either a cylindrical or cubic specimen as determined by standard test procedures.
The strengths of concrete is dictated by its function. Very low-strength—14 MPa (2,000 psi) or less—concrete may be used when the concrete must be lightweight. [ 106 ] Lightweight concrete is often achieved by adding air, foams, or lightweight aggregates, with the side effect that the strength is reduced. For most routine uses, 20 to 32 MPa (2,900 to 4,600 psi) concrete is often used. 40 MPa (5,800 psi) concrete is readily commercially available as a more durable, although more expensive, option. Higher-strength concrete is often used for larger civil projects. [ 107 ] Strengths above 40 MPa (5,800 psi) are often used for specific building elements. For example, the lower floor columns of high-rise concrete buildings may use concrete of 80 MPa (11,600 psi) or more, to keep the size of the columns small. Bridges may use long beams of high-strength concrete to lower the number of spans required. [ 108 ] [ 109 ] Occasionally, other structural needs may require high-strength concrete. If a structure must be very rigid, concrete of very high strength may be specified, even much stronger than is required to bear the service loads. Strengths as high as 130 MPa (18,900 psi) have been used commercially for these reasons. [ 108 ]
The cement produced for making concrete accounts for about 8% of worldwide CO 2 emissions per year (compared to, e.g. , global aviation at 1.9%). [ 110 ] The two largest sources of CO 2 are produced by the cement manufacturing process, arising from (1) the decarbonation reaction of limestone in the cement kiln (T ≈ 950 °C), and (2) from the combustion of fossil fuel to reach the sintering temperature (T ≈ 1450 °C) of cement clinker in the kiln. The energy required for extracting, crushing, and mixing the raw materials ( construction aggregates used in the concrete production, and also limestone and clay feeding the cement kiln ) is lower. Energy requirement for transportation of ready-mix concrete is also lower because it is produced nearby the construction site from local resources, typically manufactured within 100 kilometers of the job site. [ 111 ] The overall embodied energy of concrete at roughly 1 to 1.5 megajoules per kilogram is therefore lower than for many structural and construction materials. [ 112 ]
Once in place, concrete offers a great energy efficiency over the lifetime of a building. [ 113 ] Concrete walls leak air far less than those made of wood frames. [ 114 ] Air leakage accounts for a large percentage of energy loss from a home. The thermal mass properties of concrete increase the efficiency of both residential and commercial buildings. By storing and releasing the energy needed for heating or cooling, concrete's thermal mass delivers year-round benefits by reducing temperature swings inside and minimizing heating and cooling costs. [ 115 ] While insulation reduces energy loss through the building envelope, thermal mass uses walls to store and release energy. Modern concrete wall systems use both external insulation and thermal mass to create an energy-efficient building. Insulating concrete forms (ICFs) are hollow blocks or panels made of either insulating foam or rastra that are stacked to form the shape of the walls of a building and then filled with reinforced concrete to create the structure.
Concrete buildings are more resistant to fire than those constructed using steel frames, since concrete has lower heat conductivity than steel and can thus last longer under the same fire conditions. Concrete is sometimes used as a fire protection for steel frames, for the same effect as above. Concrete as a fire shield, for example Fondu fyre , can also be used in extreme environments like a missile launch pad.
Options for non-combustible construction include floors, ceilings and roofs made of cast-in-place and hollow-core precast concrete. For walls, concrete masonry technology and Insulating Concrete Forms (ICFs) are additional options. ICFs are hollow blocks or panels made of fireproof insulating foam that are stacked to form the shape of the walls of a building and then filled with reinforced concrete to create the structure.
Concrete also provides good resistance against externally applied forces such as high winds, hurricanes, and tornadoes owing to its lateral stiffness, which results in minimal horizontal movement. However, this stiffness can work against certain types of concrete structures, particularly where a relatively higher flexing structure is required to resist more extreme forces.
As discussed above, concrete is very strong in compression, but weak in tension. Larger earthquakes can generate very large shear loads on structures. These shear loads subject the structure to both tensile and compressional loads. Concrete structures without reinforcement, like other unreinforced masonry structures, can fail during severe earthquake shaking. Unreinforced masonry structures constitute one of the largest earthquake risks globally. [ 116 ] These risks can be reduced through seismic retrofitting of at-risk buildings, (e.g. school buildings in Istanbul, Turkey). [ 117 ]
Concrete is one of the most durable building materials. It provides superior fire resistance compared with wooden construction and gains strength over time. Structures made of concrete can have a long service life. [ 118 ] Concrete is used more than any other artificial material in the world. [ 119 ] As of 2006, about 7.5 billion cubic meters of concrete are made each year, more than one cubic meter for every person on Earth. [ 120 ]
The use of reinforcement, in the form of iron was introduced in the 1850s by French industrialist François Coignet, and it was not until the 1880s that German civil engineer G. A. Wayss used steel as reinforcement. Concrete is a relatively brittle material that is strong under compression but less in tension. Plain, unreinforced concrete is unsuitable for many structures as it is relatively poor at withstanding stresses induced by vibrations, wind loading, and so on. Hence, to increase its overall strength, steel rods, wires, mesh or cables can be embedded in concrete before it is set. This reinforcement, often known as rebar, resists tensile forces. [ 122 ]
Reinforced concrete (RC) is a versatile composite and one of the most widely used materials in modern construction. It is made up of different constituent materials with very different properties that complement each other. In the case of reinforced concrete, the component materials are almost always concrete and steel. These two materials form a strong bond together and are able to resist a variety of applied forces, effectively acting as a single structural element. [ 123 ]
Reinforced concrete can be precast or cast-in-place (in situ) concrete, and is used in a wide range of applications such as; slab, wall, beam, column, foundation, and frame construction. Reinforcement is generally placed in areas of the concrete that are likely to be subject to tension, such as the lower portion of beams. Usually, there is a minimum of 50 mm cover, both above and below the steel reinforcement, to resist spalling and corrosion which can lead to structural instability. [ 122 ] Other types of non-steel reinforcement, such as Fibre-reinforced concretes are used for specialized applications, predominately as a means of controlling cracking. [ 123 ]
Precast concrete is concrete which is cast in one place for use elsewhere and is a mobile material. The largest part of precast production is carried out in the works of specialist suppliers, although in some instances, due to economic and geographical factors, scale of product or difficulty of access, the elements are cast on or adjacent to the construction site. [ 124 ] Precasting offers considerable advantages because it is carried out in a controlled environment, protected from the elements, but the downside of this is the contribution to greenhouse gas emission from transportation to the construction site. [ 123 ]
Advantages to be achieved by employing precast concrete: [ 124 ]
Due to cement's exothermic chemical reaction while setting up, large concrete structures such as dams , navigation locks , large mat foundations, and large breakwaters generate excessive heat during hydration and associated expansion. To mitigate these effects, post-cooling [ 125 ] is commonly applied during construction. An early example at Hoover Dam used a network of pipes between vertical concrete placements to circulate cooling water during the curing process to avoid damaging overheating. Similar systems are still used; depending on volume of the pour, the concrete mix used, and ambient air temperature, the cooling process may last for many months after the concrete is placed. Various methods also are used to pre-cool the concrete mix in mass concrete structures. [ 125 ]
Another approach to mass concrete structures that minimizes cement's thermal by-product is the use of roller-compacted concrete , which uses a dry mix which has a much lower cooling requirement than conventional wet placement. It is deposited in thick layers as a semi-dry material then roller compacted into a dense, strong mass.
Raw concrete surfaces tend to be porous and have a relatively uninteresting appearance. Many finishes can be applied to improve the appearance and preserve the surface against staining, water penetration, and freezing.
Examples of improved appearance include stamped concrete where the wet concrete has a pattern impressed on the surface, to give a paved, cobbled or brick-like effect, and may be accompanied with coloration. Another popular effect for flooring and table tops is polished concrete where the concrete is polished optically flat with diamond abrasives and sealed with polymers or other sealants.
Other finishes can be achieved with chiseling, or more conventional techniques such as painting or covering it with other materials.
The proper treatment of the surface of concrete, and therefore its characteristics, is an important stage in the construction and renovation of architectural structures. [ 126 ]
Prestressed concrete is a form of reinforced concrete that builds in compressive stresses during construction to oppose tensile stresses experienced in use. This can greatly reduce the weight of beams or slabs, by
better distributing the stresses in the structure to make optimal use of the reinforcement. For example, a horizontal beam tends to sag. Prestressed reinforcement along the bottom of the beam counteracts this.
In pre-tensioned concrete, the prestressing is achieved by using steel or polymer tendons or bars that are subjected to a tensile force prior to casting, or for post-tensioned concrete, after casting.
There are two different systems being used: [ 123 ]
More than 55,000 miles (89,000 km) of highways in the United States are paved with this material. Reinforced concrete , prestressed concrete and precast concrete are the most widely used types of concrete functional extensions in modern days. For more information see Brutalist architecture .
Once mixed, concrete is typically transported to the place where it is intended to become a structural item. Various methods of transportation and placement are used depending on the distances involve, quantity needed, and other details of application. Large amounts are often transported by truck, poured free under gravity or through a tremie , or pumped through a pipe. Smaller amounts may be carried in a skip (a metal container which can be tilted or opened to release the contents, usually transported by crane or hoist), or wheelbarrow, or carried in toggle bags for manual placement underwater.
Extreme weather conditions (extreme heat or cold; windy conditions, and humidity variations) can significantly alter the quality of concrete. Many precautions are observed in cold weather placement. [ 127 ] Low temperatures significantly slow the chemical reactions involved in hydration of cement, thus affecting the strength development. Preventing freezing is the most important precaution, as formation of ice crystals can cause damage to the crystalline structure of the hydrated cement paste. If the surface of the concrete pour is insulated from the outside temperatures, the heat of hydration will prevent freezing.
The American Concrete Institute (ACI) definition of cold weather placement, ACI 306, [ 128 ] is:
In Canada , where temperatures tend to be much lower during the cold season, the following criteria are used by CSA A23.1:
The minimum strength before exposing concrete to extreme cold is 500 psi (3.4 MPa). CSA A 23.1 specified a compressive strength of 7.0 MPa to be considered safe for exposure to freezing.
Concrete may be placed and cured underwater. Care must be taken in the placement method to prevent washing out the cement. Underwater placement methods include the tremie , pumping, skip placement, manual placement using toggle bags, and bagwork. [ 129 ]
A tremie is a vertical, or near-vertical, pipe with a hopper at the top used to pour concrete underwater in a way that avoids washout of cement from the mix due to turbulent water contact with the concrete while it is flowing. This produces a more reliable strength of the product. The toggle bag method is generally used for placing small quantities and for repairs. Wet concrete is loaded into a reusable canvas bag and squeezed out at the required place by the diver. Care must be taken to avoid washout of the cement and fines.
Underwater bagwork is the manual placement by divers of woven cloth bags containing dry mix, followed by piercing the bags with steel rebar pins to tie the bags together after every two or three layers, and create a path for hydration to induce curing, which can typically take about 6 to 12 hours for initial hardening and full hardening by the next day. Bagwork concrete will generally reach full strength within 28 days. Each bag must be pierced by at least one, and preferably up to four pins. Bagwork is a simple and convenient method of underwater concrete placement which does not require pumps, plant, or formwork, and which can minimise environmental effects from dispersing cement in the water. Prefilled bags are available, which are sealed to prevent premature hydration if stored in suitable dry conditions. The bags may be biodegradable. [ 130 ]
Grouted aggregate is an alternative method of forming a concrete mass underwater, where the forms are filled with coarse aggregate and the voids then completely filled from the bottom by displacing the water with pumped grout . [ 129 ]
Concrete roads are more fuel efficient to drive on, [ 131 ] more reflective and last significantly longer than other paving surfaces, yet have a much smaller market share than other paving solutions. Modern-paving methods and design practices have changed the economics of concrete paving, so that a well-designed and placed concrete pavement will be less expensive on initial costs and significantly less expensive over the life cycle. Another major benefit is that pervious concrete can be used, which eliminates the need to place storm drains near the road, and reducing the need for slightly sloped roadway to help rainwater to run off. No longer requiring discarding rainwater through use of drains also means that less electricity is needed (more pumping is otherwise needed in the water-distribution system), and no rainwater gets polluted as it no longer mixes with polluted water. Rather, it is immediately absorbed by the ground. [ citation needed ]
Cement molded into a forest of tubular structures can be 5.6 times more resistant to cracking/failure than standard concrete. The approach mimics mammalian cortical bone that features elliptical, hollow osteons suspended in an organic matrix, connected by relatively weak "cement lines". Cement lines provide a preferable in-plane crack path. This design fails via a "stepwise toughening mechanism". Cracks are contained within the tube, reducing spreading, by dissipating energy at each tube/step. [ 132 ]
The manufacture and use of concrete produce a wide range of environmental, economic and social impacts.
Grinding of concrete can produce hazardous dust . Exposure to cement dust can lead to issues such as silicosis , kidney disease, skin irritation and similar effects. The U.S. National Institute for Occupational Safety and Health in the United States recommends attaching local exhaust ventilation shrouds to electric concrete grinders to control the spread of this dust. In addition, the Occupational Safety and Health Administration (OSHA) has placed more stringent regulations on companies whose workers regularly come into contact with silica dust. An updated silica rule, which OSHA put into effect 23 September 2017 for construction companies, restricted the amount of breathable crystalline silica workers could legally come into contact with to 50 micro grams per cubic meter of air per 8-hour workday. That same rule went into effect 23 June 2018 for general industry, hydraulic fracturing and maritime. That deadline was extended to 23 June 2021 for engineering controls in the hydraulic fracturing industry. Companies which fail to meet the tightened safety regulations can face financial charges and extensive penalties. The presence of some substances in concrete, including useful and unwanted additives, can cause health concerns due to toxicity and radioactivity. Fresh concrete (before curing is complete) is highly alkaline and must be handled with proper protective equipment.
A major component of concrete is cement , a fine powder used mainly to bind sand and coarser aggregates together in concrete. Although a variety of cement types exist, the most common is " Portland cement ", which is produced by mixing clinker with smaller quantities of other additives such as gypsum and ground limestone. The production of clinker, the main constituent of cement, is responsible for the bulk of the sector's greenhouse gas emissions, including both energy intensity and process emissions. [ 133 ]
The cement industry is one of the three primary producers of carbon dioxide, a major greenhouse gas – the other two being energy production and transportation industries. On average, every tonne of cement produced releases one tonne of CO 2 into the atmosphere. Pioneer cement manufacturers have claimed to reach lower carbon intensities, with 590 kg of CO 2 eq per tonne of cement produced. [ 134 ] The emissions are due to combustion and calcination processes, [ 135 ] which roughly account for 40% and 60% of the greenhouse gases, respectively. Considering that cement is only a fraction of the constituents of concrete, it is estimated that a tonne of concrete is responsible for emitting about 100–200 kg of CO 2 . [ 136 ] [ 137 ] Every year more than 10 billion tonnes of concrete are used worldwide. [ 137 ] In the coming years, large quantities of concrete will continue to be used, and the mitigation of CO 2 emissions from the sector will be even more critical.
Concrete is used to create hard surfaces that contribute to surface runoff , which can cause heavy soil erosion, water pollution, and flooding, but conversely can be used to divert, dam, and control flooding. Concrete dust released by building demolition and natural disasters can be a major source of dangerous air pollution . Concrete is a contributor to the urban heat island effect, though less so than asphalt .
Reducing the cement clinker content might have positive effects on the environmental life-cycle assessment of concrete. Some research work on reducing the cement clinker content in concrete has already been carried out. However, there exist different research strategies. Often replacement of some clinker for large amounts of slag or fly ash was investigated based on conventional concrete technology. This could lead to a waste of scarce raw materials such as slag and fly ash. The aim of other research activities is the efficient use of cement and reactive materials like slag and fly ash in concrete based on a modified mix design approach. [ 138 ]
The embodied carbon of a precast concrete facade can be reduced by 50% when using the presented fiber reinforced high performance concrete in place of typical reinforced concrete cladding. [ 139 ] Studies have been conducted about commercialization of low-carbon concretes. Life cycle assessment (LCA) of low-carbon concrete was investigated according to the ground granulated blast-furnace slag (GGBS) and fly ash (FA) replacement ratios. Global warming potential (GWP) of GGBS decreased by 1.1 kg CO 2 eq/m 3 , while FA decreased by 17.3 kg CO 2 eq/m 3 when the mineral admixture replacement ratio was increased by 10%. This study also compared the compressive strength properties of binary blended low-carbon concrete according to the replacement ratios, and the applicable range of mixing proportions was derived. [ 140 ]
High-performance building materials will be particularly important for enhancing resilience, including for flood defenses and critical-infrastructure protection. [ 141 ] Risks to infrastructure and cities posed by extreme weather events are especially serious for those places exposed to flood and hurricane damage, but also where residents need protection from extreme summer temperatures. Traditional concrete can come under strain when exposed to humidity and higher concentrations of atmospheric CO 2 . While concrete is likely to remain important in applications where the environment is challenging, novel, smarter and more adaptable materials are also needed. [ 137 ] [ 142 ]
There have been concerns about the recycling of painted concrete due to possible lead content. Studies have indicated that recycled concrete exhibits lower strength and durability compared to concrete produced using natural aggregates. [ 147 ] [ 148 ] [ 149 ] [ 150 ] This deficiency can be addressed by incorporating supplementary materials such as fly ash into the mixture. [ 151 ]
The world record for the largest concrete pour in a single project is the Three Gorges Dam in Hubei Province, China by the Three Gorges Corporation. The amount of concrete used in the construction of the dam is estimated at 16 million cubic meters over 17 years. The previous record was 12.3 million cubic meters held by Itaipu hydropower station in Brazil. [ 152 ] [ 153 ] [ 154 ]
The world record for concrete pumping was set on 7 August 2009 during the construction of the Parbati Hydroelectric Project, near the village of Suind, Himachal Pradesh , India, when the concrete mix was pumped through a vertical height of 715 m (2,346 ft). [ 155 ] [ 156 ]
The Polavaram dam works in Andhra Pradesh on 6 January 2019 entered the Guinness World Records by pouring 32,100 cubic metres of concrete in 24 hours. [ 157 ] The world record for the largest continuously poured concrete raft was achieved in August 2007 in Abu Dhabi by contracting firm Al Habtoor-CCC Joint Venture and the concrete supplier is Unibeton Ready Mix. [ 158 ] [ 159 ] The pour (a part of the foundation for the Abu Dhabi's Landmark Tower ) was 16,000 cubic meters of concrete poured within a two-day period. [ 160 ] The previous record, 13,200 cubic meters poured in 54 hours despite a severe tropical storm requiring the site to be covered with tarpaulins to allow work to continue, was achieved in 1992 by joint Japanese and South Korean consortiums Hazama Corporation and the Samsung C&T Corporation for the construction of the Petronas Towers in Kuala Lumpur , Malaysia. [ 161 ]
The world record for largest continuously poured concrete floor was completed 8 November 1997, in Louisville , Kentucky by design-build firm EXXCEL Project Management. The monolithic placement consisted of 225,000 square feet (20,900 m 2 ) of concrete placed in 30 hours, finished to a flatness tolerance of F F 54.60 and a levelness tolerance of F L 43.83. This surpassed the previous record by 50% in total volume and 7.5% in total area. [ 162 ] [ 163 ]
The record for the largest continuously placed underwater concrete pour was completed 18 October 2010, in New Orleans, Louisiana by contractor C. J. Mahan Construction Company, LLC of Grove City, Ohio. The placement consisted of 10,251 cubic yards of concrete placed in 58.5 hours using two concrete pumps and two dedicated concrete batch plants. Upon curing, this placement allows the 50,180-square-foot (4,662 m 2 ) cofferdam to be dewatered approximately 26 feet (7.9 m) below sea level to allow the construction of the Inner Harbor Navigation Canal Sill & Monolith Project to be completed in the dry. [ 164 ]
Concrete is used as an artistic medium. [ 165 ] Its appearance is also imitated in other media: for example Congolese artist Sardoine Mia creates canvases that look like concrete surfaces. [ 166 ] | https://en.wikipedia.org/wiki/Toggle_bag_(concrete_placement) |
Togni reagent II ( 1-trifluoromethyl-1,2-benziodoxol-3(1 H )-one ) is a chemical compound used in organic synthesis for direct electrophilic trifluoromethylation . [ 1 ] [ 2 ]
Synthesis, properties, and reactivity of the compound were first described in 2006 by Antonio Togni and his coworkers at ETH Zurich . [ 3 ] The article also contains information on Togni reagent I (1,3-dihydro-3,3-dimethyl-1-(trifluoromethyl)-1,2-benziodoxole).
The synthesis consists of three steps. In the first step, 2-iodobenzoic acid is oxidized by sodium periodate and cyclized to 1-hydroxy-1,2-benziodoxol-3(1 H )-one. The target compound can then be obtained by acylation with acetic anhydride and subsequent substitution reaction with trifluoromethyltrimethylsilane . [ 4 ]
Alternatively, trichloroisocyanuric acid can be used as oxidant in the place of sodium periodate for a newer one-pot synthesis method. [ 5 ]
The compound crystallized in a monoclinic crystal structure. The space group is P2 1 /n with four molecules in the unit cell . [ 3 ] From the crystallographic data, a density of 2.365 g·cm −3 was deduced. [ 3 ]
Pure Togni reagent II is metastable at room temperature. Heating it above the melting point will lead to strong exothermic decomposition, in which trifluoroiodomethane (CF 3 I) is released. [ 4 ] The heat of composition at a temperature of 149 °C and higher has been determined to be 502 J·g −1 . [ 6 ] From recrystallization in acetonitrile , small amounts of trifluoromethyl-2-iodobenzoate and 2-iodobenzyl fluoride were observed as decomposition products. [ 4 ] Togni reagent II reacts violently with strong bases and acids, as well as reductants. [ 4 ] In tetrahydrofuran , the compound polymerizes. [ 4 ]
Togni reagent II is used for trifluoromethylation of organic compounds. For phenolates , the substitution takes place preferably in the ortho position. It is possible to obtain a second substitution by using an excess of Togni reagent II. [ 7 ]
Reactions with alcohols yield the corresponding trifluoromethyl ethers. [ 8 ]
Trifluoromethylation of alkenes is possible under copper catalysis . [ 9 ] | https://en.wikipedia.org/wiki/Togni_reagent_II |
In combinatorial mathematics, Toida's conjecture , due to Shunichi Toida in 1977, [ 1 ] is a refinement of the disproven Ádám's conjecture from 1967.
Both conjectures concern circulant graphs . These are graphs defined from a positive integer n {\displaystyle n} and a set S {\displaystyle S} of positive integers.
Their vertices can be identified with the numbers from 0 to n − 1 {\displaystyle n-1} , and two vertices i {\displaystyle i} and j {\displaystyle j} are connected by an edge
whenever their difference modulo n {\displaystyle n} belongs to set S {\displaystyle S} . Every symmetry of the cyclic group of addition modulo n {\displaystyle n} gives rise to a symmetry of the n {\displaystyle n} -vertex circulant graphs, and Ádám conjectured (incorrectly) that these are the only symmetries of the circulant graphs.
However, the known counterexamples to Ádám's conjecture involve sets S {\displaystyle S} in which some elements share non-trivial divisors with n {\displaystyle n} .
Toida's conjecture states that, when every member of S {\displaystyle S} is relatively prime to n {\displaystyle n} , then the only symmetries of the circulant graph for n {\displaystyle n} and S {\displaystyle S} are symmetries coming from the underlying cyclic group.
The conjecture was proven in the special case where n is a prime power by Klin and Poschel in 1978, [ 2 ] and by Golfand, Najmark, and Poschel in 1984. [ 3 ]
The conjecture was then fully proven by Muzychuk, Klin, and Poschel in 2001 by using Schur algebra , [ 4 ] and simultaneously by Dobson and Morris in 2002 by using the classification of finite simple groups . [ 5 ]
This number theory -related article is a stub . You can help Wikipedia by expanding it .
This graph theory -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Toida's_conjecture |
There have been many toilet-related injuries and deaths throughout history and in urban legends .
Infants and toddlers have fallen headfirst into toilet bowls and drowned. Safety devices exist to help prevent such accidents. [ 1 ] [ 2 ] Injuries to adults include bruised buttocks and tail bones, as well as dislocated hips have resulted from unexpectedly sitting on the toilet bowl rim because the seat is up or loose. Injuries can also be caused by pinching due to splits in plastic seats and/or by splinters from wooden seats, or if the toilet itself collapses or shatters under the weight of the user. Older high-tank cast-iron cisterns have been known to detach from the wall when the chain is pulled to flush, causing injuries to the user. [ 3 ] The 2000 Ig Nobel Prize in Public Health was awarded to three physicians from the Glasgow Western Infirmary for a 1993 case report on wounds sustained to the buttocks due to collapsing toilets. [ 4 ] Furthermore, injuries are frequently sustained by people who stand on toilets to reach a height, then slip and fall. There are also instances of people slipping on a wet bathroom floor or from a bath and concussing themselves on the fixture.
Toilet-related injuries are surprisingly common, with some estimates ranging as high as 40,000 in the US every year. [ 5 ] In the past, this number would have been much higher, due to the material from which toilet paper was made. This was shown in a 1935 Northern Tissue advertisement which depicted splinter-free toilet paper. [ 6 ] In 2012, 2.3 million toilets in the United States, and about 9,400 in Canada, were recalled due to faulty pressure-assist flush mechanisms which put users at risk of the fixture exploding. [ 7 ]
There are also injuries caused by animals. Some black widow spiders like to spin their web below the toilet seat because of insects that can exist in and around it. Therefore, several people have been bitten while using a toilet, particularly outhouse toilets . Although there is immediate pain at the bite site, these bites are rarely fatal. [ 8 ] The danger of spiders living beneath toilet seats is the subject of Slim Newton 's comic 1972 country song " The Redback on the Toilet Seat ".
It has been reported that in some cases rats crawl up through toilet sewer pipes and emerge in the toilet bowl, so that toilet users may be at risk of having a rat bite their buttocks. [ 9 ] Many rat exterminators do not believe this, as pipes, at generally six inches (15 centimeters) wide, are too large for rats to climb and are also very slippery. Reports by janitors are always on the top floor, and could involve the rats on the roof, entering the soil pipe through the roof vent, lowering themselves into the pipe, and then into the toilet. [ 10 ]
In May 2016, an 11-foot snake, a reticulated python , emerged from a squat toilet and bit the man using it on his penis at his home in Chachoengsao Province , Thailand . Both the victim and the python survived. [ 11 ] [ 12 ]
Some instances of toilet-related deaths are attributed to the drop in blood pressure due to the parasympathetic nervous system during bowel movements. This effect may be magnified by existing circulatory issues. It is further possible that people succumb on the toilet to chronic constipation, because the Valsalva maneuver is often dangerously used to aid in the expulsion of feces from the rectum during a bowel movement. According to Sharon Mantik Lewis, Margaret McLean Heitkemper and Shannon Ruff Dirksen, the "Valsalva maneuver occurs during straining to pass a hardened stool. If defecation is suppressed over long periods, problems can occur, such as constipation or stool impaction. Defecation can be facilitated by the Valsalva maneuver. This maneuver involves contraction of the chest muscles on a closed glottis with simultaneous contraction of the abdominal muscles." [ 13 ] This means that people can die while "straining at stool." In chapter 8 of their Abdominal Emergencies , David Cline and Latha Stead wrote that "autopsy studies continue to reveal missed bowel obstruction as an unexpected cause of death". [ 14 ]
A 2001 Sopranos episode " He is Risen " shows a fictional depiction of the risk, when the character Gigi Cestone has a heart attack on the toilet of his social club while straining to defecate. [ 15 ]
In the Victorian era , there was a perceived risk of toilets exploding. These scenarios typically include a flammable substance (either accidentally or deliberately) being introduced into the toilet water, and a lit match or cigarette igniting and exploding the toilet. [ 16 ] In 2014, Sloan's Flushmate pressure-assisted flushing system, which uses compressed air to force waste down the drain, was recalled after the company received reports of the air tank failing under pressure and shattering the porcelain. [ 17 ]
Urban legends have been reported regarding the dangers of using a toilet in a variety of situations. Several of them have been shown to be questionable. These include some cases of the presence of venomous spiders [ 38 ] but do not include the Australian redback spider who has a reputation for hiding under toilet seats. [ 39 ] These recent fears have emerged from a series of hoax emails originating in the Blush Spider hoax, which began circulating the internet in 1999. [ 40 ] Spiders have also been reported to live under seats of airplanes, however, the cleaning chemicals used in the toilets would result in an incompatibility with spider's survival. [ 41 ]
In large cities like New York City, sewer rats often have mythical status regarding size and ferocity, resulting in tales involving the rodents crawling up sewer pipes to attack an unwitting occupant. Of late, stories about terrorists booby trapping the seat to castrate their targets have begun appearing. [ 42 ] Another myth is the risk of being sucked into an aircraft lavatory as a result of vacuum pressure during a flight. [ 43 ]
37. PBS.org Elvis’ addiction was the perfect prescription for an early death | https://en.wikipedia.org/wiki/Toilet-related_injuries_and_deaths |
In health care , toileting is the act of assisting a dependent patient with their elimination needs.
Depending on a patient's condition, their toileting needs may need to be met differently. This could be by assisting the patient to walk to a toilet , to a bedside commode chair , onto a bedpan , or to provide a male patient with a urinal . A more dependent or incontinent patient may have their toileting needs met solely through the use of adult diapers . Other options are incontinence pads and urinary catheters .
Some patients can walk with assistance from another person, usually a health care worker . Aside from the need for this help, they are capable of meeting their own elimination needs.
Patients who cannot get out of bed easily but who can control their bladder and bowels are able to request a bedpan . The bedpan is placed underneath the patient, who can urinate or defecate as needed.
Some patients are able to place their own bedpans under themselves, and assistance is required only to empty them after the fact.
A urinal is much like a bedpan but only for a male, the urinal is shaped in a way that the male may use it while still in bed and remain comfortable. The urinal is also often used when input and output (I & O) must be recorded.
Incontinent patients often wear briefs to prevent their trousers from being stained by their elimination. Briefs must be checked and changed frequently.
Catheters, in this sense, are tubes that drain urine from the body. A Foley catheter , used with men and women, is inserted into the bladder . An external catheter is attached to the penis of a male patient. In the US, while Foley catheters can only be applied by a nurse or physician, external catheters can be attached by a certified nurse assistant .
Input and output (I & O) is the measure of food and fluids that enter and exit the body. Certain patients with the need are placed on I & O, and if so, their urinary output is measured.
With self-toileting patients on I & O, or those who are assisted to a regular toilet or portable commode, a receptacle is placed in the toilet bowl that catches all urine that is put out by the patient. This, in turn, is measured by the nursing staff and recorded prior to its disposal.
If the patient is using a bedpan, the nursing staff member who empties the bedpan measures the urine prior to its disposal.
Urinals usually contain measuring lines providing easy measurement. Urinals are also useful for measuring urine from other sources.
Catheters, which are frequently used when it is necessary to measure a patient's output, often have measuring lines on their bags, but these are not considered to be accurate because the bag is floppy. Urine that is emptied from a catheter must be placed in a level container (such as a urinal) in order to be measured.
In many patients, bowel movement is also measured. In some facilities, it is the standard procedure to record bowel movement of all patients.
Bowel movement is generally measured by its size (small, medium, or large), given the amount. Additionally, if a patient has diarrhea , this is recorded.
A patient who has not had a bowel movement in several days is often given laxatives . Patients who independently toilet themselves often do not report bowel movements, thereby leading them to get laxatives when they do not need them. [ citation needed ] | https://en.wikipedia.org/wiki/Toileting |
TokBox was a PaaS (Platform as a Service) company that provided hosted infrastructure, APIs and tools required to deliver enterprise-grade WebRTC capabilities. It did so primarily through its proprietary OpenTok video platform for commercial application. [ 1 ]
TokBox was founded by Serge Faguet and Ron Hose. Headquartered in the SOMA (South of Market) district in San Francisco , CA. TokBox was acquired by Telefónica Digital, a subsidiary of Telefónica , in October 2012. [ 2 ]
Server SDKs : OpenTok's server SDKs wrap the OpenTok REST API , and let developers securely generate tokens for their OpenTok applications. Officially supported libraries include: Java and PHP . Community supported and created libraries include: Python , Ruby On Rails , .NET , Node.js , Perl , Golang . [ 3 ]
Client Libraries: OpenTok's WebRTC client libraries enable video communications on a client platform. Officially supported libraries include: JavaScript , iOS and Android . Community supported and created libraries include: PhoneGap and Titanium . [ 4 ]
TokBox has a long history of active engagement with the developer community. It has sponsored numerous hackathons since 2010 such as TechCrunch Disrupt Hackathon, [ 5 ] API Hack Day [ 6 ] and Music Hack Day. [ 7 ]
PennApps , one of the largest of such events, takes place on University of Pennsylvania campus every semester. Over a thousand students from around the world competed in the September 2013 edition of PennApps . Four sophomore students from Carnegie Mellon University with no prior hackathon experience built Classity to showcase real-time lectures on the web and won the “Best Use of TokBox API” award. [ 8 ]
Added document collaboration tool— Etherpad (now owned by Google) [ citation needed ]
TokBox was the subject of controversy when 50% of their engineering staff was fired in July 2009. This happened around the time TokBox changed CEOs. The VP of Marketing is stated as saying the firings were part of the CEO's new restructuring plan. None of the original founders are currently with TokBox. [ 14 ] | https://en.wikipedia.org/wiki/TokBox |
The token bucket is an algorithm used in packet-switched and telecommunications networks . It can be used to check that data transmissions , in the form of packets , conform to defined limits on bandwidth and burstiness (a measure of the unevenness or variations in the traffic flow). It can also be used as a scheduling algorithm to determine the timing of transmissions that will comply with the limits set for the bandwidth and burstiness: see network scheduler .
The token bucket algorithm is based on an analogy of a fixed capacity bucket into which tokens , normally representing a unit of bytes or a single packet of predetermined size, are added at a fixed rate. When a packet is to be checked for conformance to the defined limits, the bucket is inspected to see if it contains sufficient tokens at that time. If so, the appropriate number of tokens, e.g. equivalent to the length of the packet in bytes, are removed ("cashed in"), and the packet is passed, e.g., for transmission. The packet does not conform if there are insufficient tokens in the bucket, and the contents of the bucket are not changed. Non-conformant packets can be treated in various ways:
A conforming flow can thus contain traffic with an average rate up to the rate at which tokens are added to the bucket, and have a burstiness determined by the depth of the bucket. This burstiness may be expressed in terms of either a jitter tolerance, i.e. how much sooner a packet might conform (e.g. arrive or be transmitted) than would be expected from the limit on the average rate, or a burst tolerance or maximum burst size, i.e. how much more than the average level of traffic might conform in some finite period.
The token bucket algorithm can be conceptually understood as follows:
Implementers of this algorithm on platforms lacking the clock resolution necessary to add a single token to the bucket every 1 / r {\displaystyle 1/r} seconds may want to consider an alternative formulation. Given the ability to update the token bucket every S milliseconds, the number of tokens to add every S milliseconds = ( r ∗ S ) / 1000 {\displaystyle (r*S)/1000} .
Over the long run the output of conformant packets is limited by the token rate, r {\displaystyle r} .
Let M {\displaystyle M} be the maximum possible transmission rate in bytes/second.
Then T max = { b / ( M − r ) if r < M ∞ otherwise {\displaystyle T_{\text{max}}={\begin{cases}b/(M-r)&{\text{ if }}r<M\\\infty &{\text{ otherwise }}\end{cases}}} is the maximum burst time, that is the time for which the rate M {\displaystyle M} is fully utilized.
The maximum burst size is thus B max = T max ∗ M {\displaystyle B_{\text{max}}=T_{\text{max}}*M}
The token bucket can be used in either traffic shaping or traffic policing . In traffic policing, nonconforming packets may be discarded (dropped) or may be reduced in priority (for downstream traffic management functions to drop if there is congestion). In traffic shaping, packets are delayed until they conform. Traffic policing and traffic shaping are commonly used to protect the network against excess or excessively bursty traffic, see bandwidth management and congestion avoidance . Traffic shaping is commonly used in the network interfaces in hosts to prevent transmissions being discarded by traffic management functions in the network.
The token bucket algorithm is also used in controlling database IO flow. [ 1 ] In it, limitation applies to neither IOPS nor the bandwidth but rather to a linear combination of both. By defining tokens to be the normalized sum of IO request weight and its length, the algorithm makes sure that the time derivative of the aforementioned function stays below the needed threshold.
The token bucket algorithm is directly comparable to one of the two versions of the leaky bucket algorithm described in the literature. [ 2 ] [ 3 ] [ 4 ] [ 5 ] This comparable version of the leaky bucket is described on the relevant Wikipedia page as the leaky bucket algorithm as a meter . This is a mirror image of the token bucket, in that conforming packets add fluid, equivalent to the tokens removed by a conforming packet in the token bucket algorithm, to a finite capacity bucket, from which this fluid then drains away at a constant rate, equivalent to the process in which tokens are added at a fixed rate.
There is, however, another version of the leaky bucket algorithm, [ 3 ] described on the relevant Wikipedia page as the leaky bucket algorithm as a queue . This is a special case of the leaky bucket as a meter, which can be described by the conforming packets passing through the bucket. The leaky bucket as a queue is therefore applicable only to traffic shaping, and does not, in general, allow the output packet stream to be bursty, i.e. it is jitter free. It is therefore significantly different from the token bucket algorithm.
These two versions of the leaky bucket algorithm have both been described in the literature under the same name. This has led to considerable confusion over the properties of that algorithm and its comparison with the token bucket algorithm. However, fundamentally, the two algorithms are the same, and will, if implemented correctly and given the same parameters, see exactly the same packets as conforming and nonconforming.
The hierarchical token bucket (HTB) is a faster replacement for the class-based queueing (CBQ) queuing discipline in Linux . [ 6 ] It is useful for limiting each client's download / upload rate so that the limited client cannot saturate the total bandwidth.
Conceptually, HTB is an arbitrary number of token buckets arranged in a hierarchy. The primary egress queuing discipline ( qdisc ) on any device is known as the root qdisc. The root qdisc will contain one class. This single HTB class will be set with two parameters, a rate and a ceil . These values should be the same for the top-level class, and will represent the total available bandwidth on the link.
In HTB, rate means the guaranteed bandwidth available for a given class and ceil (short for ceiling) indicates the maximum bandwidth that class is allowed to consume. When a class requests a bandwidth more than guaranteed, it may borrow bandwidth from its parent as long as both ceils are not reached. Hierarchical Token Bucket implements a classful queuing mechanism for the Linux traffic control system, and provides rate and ceil to allow the user to control the absolute bandwidth to particular classes of traffic as well as indicate the ratio of distribution of bandwidth when extra bandwidth become available (up to ceil).
When choosing the bandwidth for a top-level class, traffic shaping only helps at the bottleneck between the LAN and the Internet. Typically, this is the case in home and office network environments, where an entire LAN is serviced by a DSL or T1 connection. | https://en.wikipedia.org/wiki/Token_bucket |
Tokyo tanks were internally mounted self-sealing fuel tanks used in the Boeing B-17 Flying Fortress and Consolidated B-24 Liberator bombers [ 1 ] during World War II . The tanks increased the B-17's total range at combat weight with 4,000–5,000 pounds (1,800–2,300 kg) of bombs by about 1,000 miles (1,600 km) and the combat radius was doubled to about 650 miles (1,050 km). Although nicknamed " Tokyo " tanks, the name was also hyperbole in the fact that no B-17 ever had the range to bomb Japan from any base in World War II.
These fuel tanks consisted of eighteen removable containers, called cells, made of a rubberized compound, installed inside the wings of the airplane, nine to each side. The wings of the B-17 consisted of an "inboard wing" structure mounted to the fuselage which held the engines and flaps , and an "outboard wing" structure joined to the inboard wing and carrying the ailerons . The Tokyo tanks were installed on either side of the joint (a load-bearing point) where the two wing portions were connected.
Five cells, totaling 270 US gallons (1,000 L) capacity, sat side by side in the outboard wing and were joined by a fuel line to the main wing tank, which delivered fuel to the outboard engine. The sixth cell was located in the space where the wing sections joined, and the remaining three cells were located side-by-side in the inboard wing; these four cells delivered 270 US gallons (1,000 L) of fuel to the feeder tank for the inboard engine. The same arrangement was repeated on the opposite wing. The Tokyo tanks added 1,080 US gallons (4,100 L) of fuel to the 1,700 US gallons (6,400 L) already carried in the six regular wing tanks. 820 US gallons (3,100 L) could be carried in an auxiliary tank that could be mounted in the bomb bay, for a combined total of 3,600 US gallons (14,000 L).
All B-17F aircraft built by Boeing from Block 80, by Douglas from Block 25, and by Vega from Block 30 were equipped with Tokyo tanks, and the entire run of B-17Gs by all three manufacturers had Tokyo tanks. B-17s with factory-mounted Tokyo tanks were first introduced to the Eighth Air Force in England in April 1943 with the arrival of the 94th and 95th Bomb Groups, equipped with new aircraft. By June 1943, aircraft that were so equipped began to appear in greater numbers as replacement aircraft and with new groups moving to England. Beginning in July 1943, all replacement aircraft that did not have the tanks already installed were equipped before issue.
Although the tanks were removable, this could only be done by first removing the wing panels, and so was not a routine maintenance task. A drawback to the tanks was that there was no means of measuring remaining fuel quantity within the cells. Fuel was moved from the cells to the engine feeder tanks by opening control valves within the bomb bay so that the fuel drained by gravity. Although the tanks were specified as self-sealing, vapor buildup within partially-drained tanks made them explosive hazards in combat, such as when struck by flak or cannon shells. | https://en.wikipedia.org/wiki/Tokyo_tanks |
Tolaasin , a toxic secretion by Pseudomonas tolaasii , is the cause of bacterial brown blotch disease of edible mushrooms. [ 1 ] Tolaasin is composed of 18 amino acids, including a beta-hydroxy-octanoic acid chain located at the N terminus. [ 2 ] [ 3 ] Tolaasin is a 1985 Da lipodepsipeptide non-host specific toxin. In addition to forming an amphipathic left handed alpha-helix in a hydrophobic environment, [ 4 ] the toxin has been shown to form Zn 2+ -sensitive voltage-gated ion channels in planar lipid bilayers and to catalyze erythrocyte lysis by a colloid osmotic mechanism. [ 5 ] At high concentrations, tolaasin acts as a detergent that is able to directly dissolve eukaryotic membranes . [ 1 ] The fungal cell membranes are disrupted by the lipopeptides through the formation of trans-membrane pores. [ 3 ] Tolaasin pores disrupt the cellular osmotic pressure, leading to membrane collapse. Compounds that inhibit the toxicity of tolaasin have been identified from varying food additives. Tolaasin cytotoxicity can be effectively inhibited by food detergents, as well as sucrose and polyglycerol esters of fatty acids. [ 6 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Tolaasin |
Tolerable daily intake ( TDI ) refers to the daily amount of a chemical contaminant that has been assessed safe for human exposure on long-term basis (usually whole lifetime). [ 1 ] TDI specifically occurs to chemicals that humans are exposed to unintentionally or as a contaminant, [ 1 ] where acceptable daily intake refers to chemicals that are intentional added. [ 2 ] TDI is generally written as a value of exposure (e.g. in milligrams) per kilogram (kg) body weight. [ 3 ] Both ADI and TDI are usually assessed based on animal experiments , and it is most often hundreds of times lower than the dose causing no observable adverse effect (NOAEL) in the most sensitive tested animal species. [ 2 ] [ 4 ] Because the confounding factors (safety factors) may vary depending on the quality of data and the type of adverse effect , TDI values are not good estimates of the harmfulness of chemicals, and must be considered administrative tools to set allowable limits for chemicals, rather than scientific measures . The threshold limit value (TLV) of a chemical substance is a level to which it is believed a worker can be exposed day after day for a working lifetime without adverse effects.
The World Health Organization (WHO) has introduced a TDI for melamine as 0.2 milligrams (mg)/kg body weight (b.w.) as of 2008. [ 5 ] Similarly the established TDI range for dioxins according to WHO is 1-4 picograms toxic equivalency/kg body weight as of 1998. [ 6 ] WHO's provisional maximum tolerable daily intake for all sources of iodine combined is 0.017 mg/kg b.w. [ 7 ]
The Canadian Government Health Protection Branch also uses tolerable daily intake. [ 8 ] They have established TDI's for a wide variety of chemicals, listed below.
840 micrograms/litre (drinking water) [ 8 ]
The United States Food and Drug Administration has used TDI for substances such as melamine , which is currently set at 0.063 mg/kg b.w./day. [ 9 ]
The European Food Safety Authority has set a TDI for Bisphenol A at 0.2 nanograms per kilogram of b.w./day as of 2023.
As of 2011, the Taiwan Food and Drug Administration follows the TDI values set by the European Food Safety Administrations. [ 10 ] This change was prompted by a 2011 food scandal where citizens where exposed to DEHP ( di-2-ethylhexyl phthalate ) after its intentional addition to food products. [ 10 ]
The Official Journal of Korean Society of Toxicology as requested by the Korean National Institute for Food and Drug Safety Evaluation has recommend a TDI for BPA to be set at 0.05 mg/kg b.w./day. [ 11 ]
Recommended daily allowance
Tolerable weekly intake
Acceptable daily intake | https://en.wikipedia.org/wiki/Tolerable_daily_intake |
Tolerable weekly intake ( TWI ) estimates the amount per unit body weight of a potentially harmful substance or contaminant in food or water that can be ingested over a lifetime without risk of adverse health effects. [ 1 ] [ 2 ] TWI is generally preceded by "provisional" to indicate insufficient data exists, increasing uncertainty. [ 3 ] The term TWI should be reserved for when there is a well-established and internationally accepted tolerance, backed by sound and uncontested data. Although similar in concept to tolerable daily intake (TDI), which is of the same derivation of acceptable daily intakes (ADIs), TWI accounts for contaminants that do not clear the body quickly and may accumulate within the body over a period of time. [ 3 ] An example is heavy metals such as arsenic, cadmium, lead, and mercury. [ 4 ] The concept of TWI takes into account daily variations in human consumption patterns.
Governments and international organizations such as the Joint FAO/WHO Expert Committee on Food Additives (JECFA), the Joint FAO/WHO Meeting on Pesticide Residues (JMPR), the World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO) generally use the safety factor approach, based on ADI, to determine intake tolerances for substances that exhibit thresholds for toxicity. [ 3 ] The Codex Alimentarius Commission, with the help of independent international risk assessment bodies or ad-hoc consultations organized by FAO and WHO, develops and publishes tolerances based on the best available science. [ 5 ] After identifying a substance of concern, researchers and experts then study information the substance's metabolism by humans and animals (as appropriate), the substance's toxicokinetics and toxicodynamics (including carry-over of the toxic substance from feed to edible animal tissue/products); and the substance's acute and long term toxicity in order to determine the acceptability and safety of intake levels of the substance. [ 6 ] In comparison to TWI, the Codex maximum level (ML) for a food is the maximum concentration of that substance recommended by the Codex Alimentarius Commission (CAC) to be legally permitted in that commodity. [ 6 ]
Tolerable intake is usually expressed in micrograms or milligrams per kilogram of body weight. Intake (exposure) is determined using the following formula:
Exposure = Σ i (consumption) i x (concentration) i / Body Weight | https://en.wikipedia.org/wiki/Tolerable_weekly_intake |
Tolerance analysis is the general term for activities related to the study of accumulated variation in mechanical parts and assemblies. Its methods may be used on other types of systems subject to accumulated variation, such as mechanical and electrical systems. Engineers analyze tolerances for the purpose of evaluating geometric dimensioning and tolerancing (GD&T). Methods include 2D tolerance stacks, 3D Monte Carlo simulations , and datum conversions.
Tolerance stackups or tolerance stacks are used to describe the problem-solving process in mechanical engineering of calculating the effects of the accumulated variation that is allowed by specified dimensions and tolerances . Typically these dimensions and tolerances are specified on an engineering drawing. Arithmetic tolerance stackups use the worst-case maximum or minimum values of dimensions and tolerances to calculate the maximum and minimum distance (clearance or interference) between two features or parts. Statistical tolerance stackups evaluate the maximum and minimum values based on the absolute arithmetic calculation combined with some method for establishing likelihood of obtaining the maximum and minimum values, such as Root Sum Square (RSS) or Monte-Carlo methods.
In performing a tolerance analysis, there are two fundamentally different analysis tools for predicting stackup variation: worst-case analysis and statistical analysis.
Worst-case tolerance analysis is the traditional type of tolerance stackup calculation. The individual variables are placed at their tolerance limits in order to make the measurement as large or as small as possible. The worst-case model does not consider the distribution of the individual variables, but rather that those variables do not exceed their respective specified limits. This model predicts the maximum expected variation of the measurement. Designing to worst-case tolerance requirements guarantees 100 percent of the parts will assemble and function properly, regardless of the actual component variation. The major drawback is that the worst-case model often requires very tight individual component tolerances. The obvious result is expensive manufacturing and inspection processes and/or high scrap rates. Worst-case tolerancing is often required by the customer for critical mechanical interfaces and spare part replacement interfaces. When worst-case tolerancing is not a contract requirement, properly applied statistical tolerancing can ensure acceptable assembly yields with increased component tolerances and lower fabrication costs.
The statistical variation analysis model takes advantage of the principles of statistics to relax the component tolerances without sacrificing quality. Each component's variation is modeled as a statistical distribution and these distributions are summed to predict the distribution of the assembly measurement. Thus, statistical variation analysis predicts a distribution that describes the assembly variation, not the extreme values of that variation. This analysis model provides increased design flexibility by allowing the designer to design to any quality level, not just 100 percent.
There are two chief methods for performing the statistical analysis. In one, the expected distributions are modified in accordance with the relevant geometric multipliers within tolerance limits and then combined using mathematical operations to provide a composite of the distributions. The geometric multipliers are generated by making small deltas to the nominal dimensions. The immediate value to this method is that the output is smooth, but it fails to account for geometric misalignment allowed for by the tolerances; if a size dimension is placed between two parallel surfaces, it is assumed the surfaces will remain parallel, even though the tolerance does not require this. Because the CAD engine performs the variation sensitivity analysis, there is no output available to drive secondary programs such as stress analysis.
In the other, the variations are simulated by allowing random changes to geometry, constrained by expected distributions within allowed tolerances with the resulting parts assembled, and then measurements of critical places are recorded as if in an actual manufacturing environment. The collected data is analyzed to find a fit with a known distribution and mean and standard deviations derived from them. The immediate value to this method is that the output represents what is acceptable, even when that is from imperfect geometry and, because it uses recorded data to perform its analysis, it is possible to include actual factory inspection data into the analysis to see the effect of proposed changes on real data. In addition, because the engine for the analysis is performing the variation internally, not based on CAD regeneration, it is possible to link the variation engine output to another program. For example, a rectangular bar may vary in width and thickness; the variation engine could output those numbers to a stress program which passes back peak stress as a result and the dimensional variation be used to determine likely stress variations. The disadvantage is that each run is unique, so there will be variation from analysis to analysis for the output distribution and mean, just like would come from a factory.
While no official engineering standard covers the process or format of tolerance analysis and stackups, these are essential components of good product design . Tolerance stackups should be used as part of the mechanical design process, both as a predictive and a problem-solving tool. The methods used to conduct a tolerance stackup depend somewhat upon the engineering dimensioning and tolerancing standards that are referenced in the engineering documentation, such as American Society of Mechanical Engineers (ASME) Y14.5, ASME Y14.41, or the relevant ISO dimensioning and tolerancing standards. Understanding the tolerances, concepts and boundaries created by these standards is vital to performing accurate calculations.
Tolerance stackups serve engineers by:
The starting point for the tolerance loop; typically this is one side of an intended gap, after pushing the various parts in the assembly to one side or another of their loose range of motion. Vector loops define the assembly constraints that locate the parts of the assembly relative to each other. The vectors represent the dimensions that contribute to tolerance stackup in the assembly. The vectors are joined tip-to-tail, forming a chain, passing through each part in the assembly in succession. A vector loop must obey certain modeling rules as it passes through a part. It must:
Additional modeling rules for vector loops include:
The above rules will vary depending on whether 1D, 2D or 3D tolerance stackup method is used.
A safety factor is often included in designs because of concerns about: | https://en.wikipedia.org/wiki/Tolerance_analysis |
Tolerance to infection , or disease tolerance, is a mechanism that host organisms can use to fight parasites or pathogens that attack the host. Tolerance is not equivalent to resistance. Disease resistance is the host trait that prevents infection or reduces the number of pathogens and parasites within or on a host.
Tolerance to infection can be illustrated via comparing host performance versus increasing load. This is a reaction norm in which host performance is regressed against increasing disease burden. [ 1 ] The slope of the reaction norm defines the degree of tolerance. High tolerance is indicated as a flat slope, i.e., host performance is not influenced by increasing burden. Steep downward slope indicates low tolerance in which host performance is strongly reduced with increasing burden. An upward slope indicates overcompensation in which a host increases its performance with increasing burden. Genetic variation in tolerance and its correlation with resistance, can be quantified using random regression model. [ 2 ]
In livestock science, tolerance to infections is sometimes termed disease resilience. [ 4 ] [ 5 ]
A variety of reactions to pathogens are thought to be involved in tolerance, including superior immune system regulation and supplying pathogens with sufficient nutrients to blunt attacks on cells. [ 6 ]
Humans experience tolerance. For example, 90% of people infected with tuberculosis experience no symptoms. [ 7 ] Similarly, many humans tolerate helminth infestations. [ 6 ]
Much research makes use of the lethal dose 50 protocol. Subjects are given enough pathogen to kill half of them. The remaining half presumably exhibit the desired tolerance. In many cases, the survivors not only survive but are unaffected by the pathogen.
Research is complicated by the fact that animal protocols typically involve expecting some of the subjects to die, which is not ethical in humans. [ 6 ] | https://en.wikipedia.org/wiki/Tolerance_to_infections |
In mathematical logic , a tolerant sequence is a sequence
of formal theories such that there are consistent extensions
of these theories with each S i + 1 {\displaystyle S_{i+1}} interpretable in S i {\displaystyle S_{i}} . Tolerance naturally generalizes from sequences of theories to trees of theories. Weak interpretability can be shown to be a special, binary case of tolerance.
This concept, together with its dual concept of cotolerance , was introduced by Japaridze in 1992, who also proved that, for Peano arithmetic and any stronger theories with effective axiomatizations, tolerance is equivalent to Π 1 {\displaystyle \Pi _{1}} -consistency. | https://en.wikipedia.org/wiki/Tolerant_sequence |
Tolerogenic dendritic cells (a. k. a. tol-DCs , tDCs , or DCregs ) are heterogenous pool of dendritic cells with immuno-suppressive properties, priming immune system into tolerogenic state against various antigens . These tolerogenic effects are mostly mediated through regulation of T cells such as inducing T cell anergy , T cell apoptosis and induction of Tregs . [ 1 ] Tol-DCs also affect local micro-environment toward tolerogenic state by producing anti-inflammatory cytokines .
Tol-DCs are not lineage specific and their immune-suppressive functions is due to their state of activation and/or differentiation. Generally, properties of all types of dendritic cells can be highly affected by local micro-environment such as presence of pro or anti-inflammatory cytokines, therefore tolerogenic properties of tol-DCs are often context dependant and can be even eventually overridden into pro-inflammatory phenotype . [ 2 ] [ 3 ] [ 4 ]
Tolerogenic DCs present a potential strategy for treatment of autoimmune diseases, allergic diseases and transplant rejections. Moreover, Ag-specific tolerance in humans can be induced in vivo via vaccination with Ag-pulsed ex vivo generated tolerogenic DCs. [ 5 ] For that reason, tolerogenic DCs are an important promising therapeutic tool. [ 6 ]
Dendritic cells (DCs) were first discovered and described in 1973 by Ralph M. Steinman . They represent a bridge between innate and adaptive immunity and play a key role in the regulation of initiation of immune responses. DCs populate almost all body surfaces and they do not kill the pathogens directly, they utilize and subsequently degrade antigens to peptides by their proteolytic activity. After that, they present these peptides in complexes together with their MHC molecules on their cell surface. DCs are also the only cell type which can activate naïve T cells and induce antigen-specific immune responses. [ 6 ] [ 7 ]
Therefore, their role is crucially important in balance between tolerance and immune response.
Tolerogenic DCs are essential in maintenance of central and peripheral tolerance through induction of T cell clonal deletion, T cell anergy and generation and activation of regulatory T (Treg) cells. For that reason, tolerogenic DCs are possible candidates for specific cellular therapy for treatment of allergic diseases, autoimmune diseases (e.g. type 1 diabetes, multiple sclerosis, rheumatoid arthritis) or transplant rejections. [ 8 ] [ 9 ] [ 6 ]
Tolerogenic DCs often display an immature or semi-mature phenotype with characteristically low expression of costimulatory (e.g. CD80, CD86) and MHC molecules on their surface. Tolerogenic DCs also produce different cytokines as mature DCs (e.g. anti-inflammatory cytokines interleukin (IL)-10, transforming growth factor-β (TGF-β)). Moreover, tolerogenic DCs may also express various inhibitory surface molecules (e.g. programmed cell death ligand (PDL)-1, PDL-2) or can modulate metabolic parameters and change T cell response. For example, tolerogenic DCs can release or induce enzymes such as indoleamine 2,3-dioxygenase (IDO) or heme oxygenase-1 (HO-1). IDO promotes the degradation of tryptophan to N-formylkynurenin leading to reduced T cell proliferation, whereas HO- 1 catalyzes degradation of hemoglobin resulting in production of monoxide and lower DC immunogenicity. Besides that, tolerogenic DCs also may produce retinoic acid (RA), which induces Treg differentiation. [ 10 ] [ 11 ]
Human tolerogenic DCs may be induced by various immunosuppressive drugs or biomediators. Immunosuppressive drugs, e.g. corticosteroid dexamethasone, rapamycin, cyclosporine or acetylsalicylic acid, cause low expression of costimulatory molecules, reduced expression of MHC, higher expression of inhibitory molecules (e.g. PDL-1) or higher secretion of IL-10 or IDO. In addition, incubation with inhibitory cytokines IL-10 or TGF-β leads to generation of tolerogenic phenotype. Other mediators also affect generation of tolerogenic DC, e.g. vitamin D3, vitamin D2, [ 12 ] hepatocyte growth factor or vasoactive intestinal peptide. The oldest and mostly used cytokine cocktail for in vitro DC generation is GM-CSF/IL-4. [ 10 ] [ 5 ]
Tolerogenic DCs may be a potential candidate for specific immunotherapy and are studied for using them for treatment of inflammatory, autoimmune and allergic diseases and also in transplant medicine. Important and interesting feature of tolerogenic DCs is also the migratory capacity toward secondary lymph organs, leading to T-cell mediated immunosuppression. The first trial to transfer tolerogenic DCs to humans was undertaken by Ralph Steinman's group in 2001. Relating to the DC administration, various application have been used in humans in last years. Tolerogenic DCs have been injected e.g. intraperitoneally in patients with Crohn's disease, intradermally in diabetes and rheumatoid arthritis patients, subcutaneously in rheumatoid arthritis patients and via arthroscopic injections in joints of patient with rheumatoid and inflammatory arthritis. [ 13 ]
Therefore, it is necessary to test tolerogenic DCs for a stable phenotype to exclude a loss of the regulatory function and a switch to an immunostimulatory activity.
Despite tol-DCs not being lineage specific, they generally express more cell-surface immuno-suppressive molecules and factors in comparison with immunogenic co-stimulatory molecules. Higher expression of inhibitory molecules is associated with their tolerogenic abilities.
These molecules are: PD-L1, immunoglobulin like transcripts ILT (ILT3/4/5), B7-H1 , SLAM, DEC-205 . [ 14 ] [ 15 ] [ 16 ] [ 17 ] Tolerogenic effect has been demonstrated also by over-expression of Jagged-1 on DCs which in turn induced antigen specific T regulatory cells producing TGF-b . [ 18 ]
Tol-DCs promotes central and peripheral tolerance. These tolerogenic properties are executed by deletion of T cells, induction of Tregs and anergized T cells, then by expression of immunomodulatory molecules such as PD-L1 and PD-L2 , heme oxygenase 1 , HLA-G , CD95L , TNF-related apoptosis inducing ligands , galectin-1 and DC-SIGN and production of immunosuppressive molecules such as IL-10 , TGF-b, indoleamine 2,3-dioxygenase (IDO), IL-27 and NO. [ 19 ] [ 20 ] [ 21 ] [ 22 ]
Tol-DCs can be induced by various stimuli. It has been shown that following molecules induce/promote/favour induction of tol-DCs: IL-10, IL-27, TGF-b1, hepatocyte growth factor , vasoactive intestinal peptide , retinoid acid , vitamin D3 , corticosteroids , rapamycin , cyclosporine , tacrolism , aspirin and ligands of AhR . [ 23 ] [ 24 ]
Currently are characterized two subpopulations of human tolerogenic DCs: CD83 high CCR7 + and CD83 low CCR7 − IL-10DCs. CD83 high IL-10DCs display a stable phenotype under inflammatory conditions and show higher migratory capacity, providing migration to secondary lymphoid organs. Therefore, CD83 high IL-10DCs could be promising and great candidates for tolerance-inducing vaccination studies in vivo . [ 5 ]
In 2011, Giannoukakis et al. published results of randomized, double-blind phase I study of autologous DCs vaccination in type I diabetic patients. Treatment with these cells was safe and well tolerated. [ 25 ]
The whole pool of tolerogenic dendritic cells can be divided in two large groups - Naturally occurring tolerogenic DCs and induced tolerogenic DCs.
Natural tol-DCs are mostly present in site of tolerogenic environment. They are maintained in their tolerogenic state by anti-inflammatory cytokines presented in those environments, but they can be easily overridden by inflammatory signals into being immunogenic. [ 23 ] They can be found in intestinal, pulmonary, cutaneous, blood and hepatic tissues. It is yet expected they will be found even elsewhere. [ 3 ]
Their tolerogenic effect is mostly due to their lack of immunogenic co-stimulatory molecules despite their ability to present antigens. This phenomenon results in T cells anergy. [ 3 ] Repetitive stimulation of T cells by iDCs can convert them into Tregs [ 26 ] [ 27 ] Immature and semimature dendritic cells are tolerogenic under steady-state conditions and once exposed to pro-inflammatory milieu they can also become immunogenic. [ 28 ] [ 29 ]
Tol-DCs can be induced by chemicals, pathological conditions or molecular modifications.
Certain pathogens are capable of hijacking host immune tolerance and induce Tregs in their surroundings. [ 30 ] [ 31 ] [ 32 ]
Tumours also developed ways of inducing tol-DCs resulting in differentiation and accumulation of Tregs in their stroma and draining lymph node. [ 33 ] [ 34 ]
As already mentioned above many pharmacological substances are capable of inducing tol-DCs including corticosteroids, rapamycin, cyclosporine, tacrolism, aspirin,.
Genetic manipulations can used to confer tolerogenic properties on DCs such as gene knock down, knock-out, transgenic over expression of proteins and others. [ 35 ] | https://en.wikipedia.org/wiki/Tolerogenic_dendritic_cell |
Tolivirales is an order of RNA viruses which infect insects and plants . [ 1 ] Member viruses have a positive-sense single-stranded RNA genome . The virions are non-enveloped , spherical, and have an icosahedral capsid . [ 2 ] [ 3 ] [ 4 ] The name of the group is a syllabic abbreviation of " to mbusvirus- li ke" with the suffix -virales indicating a virus order . [ 5 ]
The following families are recognized:
This virus -related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Tolivirales |
Toll-like receptors ( TLRs ) are a class of proteins that play a key role in the innate immune system . They are single-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells , that recognize structurally conserved molecules derived from microbes . Once these microbes have reached physical barriers such as the skin or intestinal tract mucosa , they are recognized by TLRs, which activate immune cell responses. The TLRs include TLR1 , TLR2 , TLR3 , TLR4 , TLR5 , TLR6 , TLR7 , TLR8 , TLR9 , TLR10 , TLR11 , TLR12 , and TLR13 . Humans lack genes for TLR11, TLR12 and TLR13 [ 1 ] and mice lack a functional gene for TLR10. [ 2 ] The receptors TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are located on the cell membrane , whereas TLR3, TLR7, TLR8, and TLR9 are located in intracellular vesicles (because they are sensors of nucleic acids ). [ 3 ]
TLRs received their name from their similarity to the protein coded by the toll gene . [ 4 ]
The ability of the immune system to recognize molecules that are broadly shared by pathogens is, in part, due to the presence of immune receptors called toll-like receptors (TLRs) that are expressed on the membranes of leukocytes including dendritic cells , macrophages , natural killer cells , cells of the adaptive immunity T cells , and B cells , and non-immune cells ( epithelial and endothelial cells , and fibroblasts ). [ 5 ]
The binding of ligands — either in the form of adjuvant used in vaccinations or in the form of invasive moieties during times of natural infection — to the TLR marks the key molecular events that ultimately lead to innate immune responses and the development of antigen-specific acquired immunity. [ 6 ] [ 7 ]
Upon activation, TLRs recruit adaptor proteins (proteins that mediate other protein-protein interactions) within the cytosol of the immune cell to propagate the antigen-induced signal transduction pathway . These recruited proteins are then responsible for the subsequent activation of other downstream proteins, including protein kinases (IKKi, IRAK1 , IRAK4 , and TBK1 ) that further amplify the signal and ultimately lead to the upregulation or suppression of genes that orchestrate inflammatory responses and other transcriptional events. Some of these events lead to cytokine production, proliferation , and survival, while others lead to greater adaptive immunity. [ 7 ] If the ligand is a bacterial factor, the pathogen might be phagocytosed and digested, and its antigens presented to CD4+ T cells .
In the case of a viral factor, the infected cell may shut off its protein synthesis and may undergo programmed cell death ( apoptosis ). Immune cells that have detected a virus may also release anti-viral factors such as interferons .
Toll-like receptors have also been shown to be an important link between innate and adaptive immunity through their presence in dendritic cells . [ 8 ] Flagellin , a TLR5 ligand, induces cytokine secretion on interacting with TLR5 on human T cells. [ 8 ]
TLRs are a type of pattern recognition receptor (PRR) and recognize molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs). In addition to the recognition of exogenous PAMPs, TLRs can also bind to endogenous damage-associated molecular patterns (DAMPs) such as heat shock proteins (HSPs) or plasma membrane constituents. [ 9 ] TLRs together with the Interleukin-1 receptors form a receptor superfamily , known as the "interleukin-1 receptor / toll-like receptor superfamily"; all members of this family have in common a so-called TIR (toll-IL-1 receptor) domain.
Three subgroups of TIR domains exist. Proteins with subgroup 1 TIR domains are receptors for interleukins that are produced by macrophages , monocytes , and dendritic cells and all have extracellular Immunoglobulin (Ig) domains. Proteins with subgroup 2 TIR domains are classical TLRs, and bind directly or indirectly to molecules of microbial origin. A third subgroup of proteins containing TIR domains consists of adaptor proteins that are exclusively cytosolic and mediate signaling from proteins of subgroups 1 and 2.
TLRs are present in vertebrates as well as invertebrates . Molecular building blocks of the TLRs are represented in bacteria and in plants, and plant pattern recognition receptors are well known to be required for host defence against infection. The TLRs thus appear to be one of the most ancient, conserved components of the immune system .
In recent years TLRs were identified also in the mammalian nervous system. Members of the TLR family were detected on glia, neurons and on neural progenitor cells in which they regulate cell-fate decision. [ 10 ]
It has been estimated that most mammalian species have between ten and fifteen types of toll-like receptors. Thirteen TLRs (named simply TLR1 to TLR13) have been identified in humans and mice together, and equivalent forms of many of these have been found in other mammalian species. [ 11 ] [ 12 ] [ 13 ] However, equivalents of certain TLR found in humans are not present in all mammals. For example, a gene coding for a protein analogous to TLR10 in humans is present in mice , but appears to have been damaged at some point in the past by a retrovirus . On the other hand, mice express TLRs 11, 12, and 13, none of which is represented in humans. Other mammals may express TLRs that are not found in humans. Other non-mammalian species may have TLRs distinct from mammals, as demonstrated by the anti-cell-wall TLR14 , which is found in the Takifugu pufferfish. [ 14 ] This may complicate the process of using experimental animals as models of human innate immunity.
Vertebrate TLRs are divided by similarity into the families of TLR 1/2/6/10/14/15, TLR 3, TLR 4, TLR 5, TLR 7/8/9, and TLR 11/12/13/16/21/22/23. [ 14 ]
The involvement of toll signalling in immunity was first demonstrated in the fruit fly, Drosophila melanogaster . [ 19 ] Fruit flies have only innate immune responses allowing studies to avoid interference of adaptive immune mechanisms on signal transduction. The fly response to fungal or bacterial infection occurs through two distinct signalling cascades, one of which is the toll pathway and the other is the immune deficiency pathway . The toll pathway is similar to mammalian TLR signalling, but unlike mammalian TLRs, toll is not activated directly by pathogen-associated molecular patterns ( PAMPs ). Its receptor ectodomain recognizes the cleaved form of the cytokine spätzle, which is secreted in the haemolymph as an inactive dimeric precursor. The toll receptor shares the cytoplasmatic TIR domain with mammalian TLRs, but the ectodomain and intracytoplasmatic tail are different. This difference might reflect a function of these receptors as cytokine receptors rather than PRRs .
The toll pathway is activated by different stimuli, such as gram-positive bacteria , fungi, and virulence factors . [ 17 ] [ 20 ] First, the Spätzle processing enzyme (SPE) is activated in response to infection and cleaves spätzle ( spz ). Cleaved spätzle then binds to the toll receptor and crosslinks its ectodomains. This triggers conformational changes in the receptor resulting in signalling through toll. From this point forward, the signalling cascade is very similar to mammalian signalling through TLRs. The toll-induced signalling complex (TICS) is composed of MyD88 , Tube, and Pelle (the orthologue of mammalian IRAK). Signal from TICS is then transduced to Cactus (homologue of mammalian IκB ), phosphorylated Cactus is polyubiquitylated and degraded, allowing nuclear translocation of DIF (dorsal-related immunity factor; a homologue of mammalian NF-κB ) and induction of transcription of genes for antimicrobial peptides (AMPs) such as drosomycin . [ 21 ]
Drosophila have a total of 9 toll family and 6 spz family genes that interact with each other to differing degrees. [ 22 ]
TLR2 has also been designated as CD282 (cluster of differentiation 282).
TLR3 does not use the MyD88 dependent pathway. Its ligand is retroviral double-stranded RNA ( dsRNA ), which activates the TRIF dependent signalling pathway. To explore the role of this pathway in retroviral reprograming, knock down techniques of TLR3 or TRIF were prepared, and results showed that only the TLR3 pathway is required for full induction of target gene expression by the retrovirus expression vector. This retroviral expression of four transcriptional factors ( Oct4 , Sox2 , Klf4 and c-Myc ; OSKM) induces pluripotency in somatic cells. This is supported by study, which shows, that efficiency and amount of human iPSC generation, using retroviral vectors, is reduced by knockdown of the pathway with peptide inhibitors or shRNA knockdown of TLR3 or its adaptor protein TRIF. Taken together, stimulation of TLR3 causes great changes in chromatin remodeling and nuclear reprogramming, and activation of inflammatory pathways is required for these changes, induction of pluripotency genes and generation of human induced pluripotent stem cells (iPSC) colonies. [ 23 ]
As noted above, human cells do not express TLR11 , but mice cells do. Mouse-specific TLR11 recognizes uropathogenic E.coli and the apicomplexan parasite Toxoplasma gondii . With Toxoplasma its ligand is the protein profilin and the ligand for E. coli is flagellin . The flagellin from the enteropathogen Salmonella is also recognized by TLR11. [ 24 ]
As mouse TLR11 is able to recognize Salmonella effectively, normal mice do not get infected by oral Salmonella Typhi , which causes food- and waterborne gastroenteritis and typhoid fever in humans. TLR11 deficient knockout mice , on the other hand, are efficiently infected. As a result, this knockout mouse can act as a disease model of human typhoid fever. [ 25 ]
Toll-like receptors bind and become activated by different ligands, which, in turn, are located on different types of organisms or structures. They also have different adapters to respond to activation and are located sometimes at the cell surface and sometimes to internal cell compartments . [ 26 ] Furthermore, they are expressed by different types of leucocytes or other cell types :
Because of the specificity of toll-like receptors (and other innate immune receptors) they cannot easily be changed in the course of evolution, these receptors recognize molecules that are constantly associated with threats (i.e., pathogen or cell stress) and are highly specific to these threats (i.e., cannot be mistaken for self molecules that are normally expressed under physiological conditions). Pathogen-associated molecules that meet this requirement are thought to be critical to the pathogen's function and difficult to change through mutation; they are said to be evolutionarily conserved. Somewhat conserved features in pathogens include bacterial cell-surface lipopolysaccharides (LPS), lipoproteins , lipopeptides, and lipoarabinomannan ; proteins such as flagellin from bacterial flagella ; double-stranded RNA of viruses; or the unmethylated CpG islands of bacterial and viral DNA ; and also of the CpG islands found in the promoters of eukaryotic DNA; as well as certain other RNA and DNA molecules. As TLR ligands are present in most pathogens, they may also be present in pathogen-derived vaccines (e.g. MMR, influenza, polio vaccines) most commercially available vaccines have been assessed for their inherent TLR ligands' capacity to activate distinct subsets of immune cells. [ 46 ] [ 47 ] For most of the TLRs, ligand recognition specificity has now been established by gene targeting (also known as "gene knockout"): a technique by which individual genes may be selectively deleted in mice. [ 48 ] [ 49 ] See the table above for a summary of known TLR ligands.
The stereotypic inflammatory response provoked by toll-like receptor activation has prompted speculation that endogenous activators of toll-like receptors might participate in autoimmune diseases. TLRs have been suspected of binding to host molecules including fibrinogen (involved in blood clotting ), heat shock proteins (HSPs), HMGB1 , extracellular matrix components and self DNA (it is normally degraded by nucleases, but under inflammatory and autoimmune conditions it can form a complex with endogenous proteins, become resistant to these nucleases and gain access to endosomal TLRs as TLR7 or TLR9). These endogenous ligands are usually produced as a result of non-physiological cell death. [ 50 ]
TLRs are believed to function as dimers . Though most TLRs appear to function as homodimers , TLR2 forms heterodimers with TLR1 or TLR6, each dimer having a different ligand specificity. TLRs may also depend on other co-receptors for full ligand sensitivity, such as in the case of TLR4's recognition of LPS , which requires MD-2. CD14 and LPS-Binding Protein ( LBP ) are known to facilitate the presentation of LPS to MD-2.
A set of endosomal TLRs comprising TLR3, TLR7, TLR8 and TLR9 recognize nucleic acid derived from viruses as well as endogenous nucleic acids in context of pathogenic events. Activation of these receptor leads to production of inflammatory cytokines as well as type I interferons ( interferon type I ) to help fight viral infection.
The adapter proteins and kinases that mediate TLR signaling have also been targeted. In addition, random germline mutagenesis with ENU has been used to decipher the TLR signaling pathways. When activated, TLRs recruit adapter molecules within the cytoplasm of cells to propagate a signal. Four adapter molecules are known to be involved in signaling. These proteins are known as MyD88 , TIRAP (also called Mal), TRIF , and TRAM (TRIF-related adaptor molecule). [ 51 ] [ 52 ] [ 53 ]
TLR signaling is divided into two distinct signaling pathways, the MyD88-dependent and TRIF-dependent pathway.
The MyD88-dependent response occurs on dimerization of TLRs, and is used by every TLR except TLR3. Its primary effect is activation of NFκB and mitogen-activated protein kinase . Ligand binding and conformational change that occurs in the receptor recruits the adaptor protein MyD88, a member of the TIR family. MyD88 then recruits IRAK4 , IRAK1 and IRAK2 . IRAK kinases then phosphorylate and activate the protein TRAF6 , which in turn polyubiquinates the protein TAK1, as well as itself to facilitate binding to IKK-β . On binding, TAK1 phosphorylates IKK-β, which then phosphorylates IκB causing its degradation and allowing NFκB to diffuse into the cell nucleus and activate transcription and consequent induction of inflammatory cytokines. [ 50 ]
Both TLR3 and TLR4 use the TRIF-dependent pathway, which is triggered by dsRNA and LPS, respectively. For TLR3, dsRNA leads to activation of the receptor, recruiting the adaptor TRIF . TRIF activates the kinases TBK1 and RIPK1 , which creates a branch in the signaling pathway. The TRIF/TBK1 signaling complex phosphorylates IRF3 allowing its translocation into the nucleus and production of interferon type I . Meanwhile, activation of RIPK1 causes the polyubiquitination and activation of TAK1 and NFκB transcription in the same manner as the MyD88-dependent pathway. [ 50 ]
TLR signaling ultimately leads to the induction or suppression of genes that orchestrate the inflammatory response. In all, thousands of genes are activated by TLR signaling, and collectively, the TLRs constitute one of the most pleiotropic yet tightly regulated gateways for gene modulation.
TLR4 is the only TLR that uses all four adaptors. Complex consisting of TLR4, MD2 and LPS recruits TIR domain-containing adaptors TIRAP and MyD88 and thus initiates activation of NFκB (early phase) and MAPK. TLR4-MD2-LPS complex then undergoes endocytosis and in endosome it forms a signaling complex with TRAM and TRIF adaptors. This TRIF-dependent pathway again leads to IRF3 activation and production of type I interferons, but it also activates late-phase NFκB activation. Both late and early phase activation of NFκB is required for production of inflammatory cytokines. [ 50 ]
Imiquimod (cardinally used in dermatology ) is a TLR7 agonist, and its successor resiquimod , is a TLR7 and TLR8 agonist. [ 54 ] Recently, resiquimod has been explored as an agent for cancer immunotherapy, [ 55 ] acting through stimulation of tumor-associated macrophages.
Several TLR ligands are in clinical development or being tested in animal models as vaccine adjuvants , [ 56 ] with the first clinical use in humans in a recombinant herpes zoster vaccine in 2017, which contains a monophosphoryl lipid A component.
TLR7 messenger RNA expression levels in dairy animals in a natural outbreak of foot-and-mouth disease have been reported. [ 57 ]
TLR4 has been shown to be important for the long-term side-effects of opioids . Its activation leads to downstream release of inflammatory modulators including TNF-α and IL-1β , and constant low-level release of these modulators is thought to reduce the efficacy of opioid drug treatment with time, and is involved in opioid tolerance, [ 58 ] [ 59 ] hyperalgesia and allodynia . [ 60 ] [ 61 ] Morphine induced TLR4 activation attenuates pain suppression by opioids and enhances the development of opioid tolerance and addiction , drug abuse , and other negative side effects such as respiratory depression and hyperalgesia. [ 62 ] Drugs that block the action of TNF-α or IL-1β have been shown to increase the analgesic effects of opioids and reduce the development of tolerance and other side-effects, [ 63 ] [ 64 ] and this has also been demonstrated with drugs that block TLR4 itself.
The "unnatural" enantiomers of opioid drugs such as (+)-morphine and (+)-naloxone lack affinity for opioid receptors, still produce the same activity at TLR4 as their "normal" enantiomers. [ 65 ] [ 66 ] So, "unnatural" entianomers of opioids such as (+)-naloxone, can be used to block the TLR4 activity of opioid analgesic drugs without having any affinity for μ-opioid receptor [ 67 ] [ 66 ] [ 68 ]
When microbes were first recognized as the cause of infectious diseases, it was immediately clear that multicellular organisms must be capable of recognizing them when infected and, hence, capable of recognizing molecules unique to microbes. A large body of literature, spanning most of the last century, attests to the search for the key molecules and their receptors. More than 100 years ago, Richard Pfeiffer , a student of Robert Koch , coined the term " endotoxin " to describe a substance produced by Gram-negative bacteria that could provoke fever and shock in experimental animals . In the decades that followed, endotoxin was chemically characterized and identified as a lipopolysaccharide (LPS) produced by most Gram-negative bacteria. This lipopolysaccharide is an integral part of the gram-negative membrane and is released upon destruction of the bacterium. Other molecules (bacterial lipopeptides , flagellin , and unmethylated DNA ) were shown in turn to provoke host responses that are normally protective. However, these responses can be detrimental if they are excessively prolonged or intense. It followed logically that there must be receptors for such molecules, capable of alerting the host to the presence of infection, but these remained elusive for many years. Toll-like receptors are now counted among the key molecules that alert the immune system to the presence of microbial infections.
The prototypic member of the family, the toll receptor ( P08953 ; Tl) in the fruit fly Drosophila melanogaster , was discovered in 1985 by 1995 Nobel Laureates Christiane Nüsslein-Volhard and Eric Wieschaus and colleagues. It was known for its developmental function in embryogenesis by establishing the dorsal - ventral axis. It was named after Christiane Nüsslein-Volhard's 1985 exclamation, " Das ist ja toll ! " ("That's amazing!"), in reference to the underdeveloped ventral portion of a fruit fly larva. [ 4 ] It was cloned by the laboratory of Kathryn Anderson in 1988. [ 69 ] In 1996, toll was found by Jules A. Hoffmann and his colleagues to have an essential role in the fly's immunity to fungal infection , which it achieved by activating the synthesis of antimicrobial peptides. [ 19 ]
The first reported human toll-like receptor was described by Nomura and colleagues in 1994, [ 70 ] mapped to a chromosome by Taguchi and colleagues in 1996. [ 71 ] Because the immune function of toll in Drosophila was not then known, it was assumed that TIL (now known as TLR1) might participate in mammalian development. However, in 1991 (prior to the discovery of TIL) it was observed that a molecule with a clear role in immune function in mammals, the interleukin-1 (IL-1) receptor, also had homology to drosophila toll; the cytoplasmic portions of both molecules were similar. [ 72 ]
In 1997, Charles Janeway and Ruslan Medzhitov showed that a toll-like receptor now known as TLR4 could, when artificially ligated using antibodies, induce the activation of certain genes necessary for initiating an adaptive immune response . [ 7 ] TLR 4 function as an LPS sensing receptor was discovered by Bruce A. Beutler and colleagues. [ 73 ] These workers used positional cloning to prove that mice that could not respond to LPS had mutations that abolished the function of TLR4. This identified TLR4 as one of the key components of the receptor for LPS.
In turn, the other TLR genes were ablated in mice by gene targeting, largely in the laboratory of Shizuo Akira and colleagues. Each TLR is now believed to detect a discrete collection of molecules — some of microbial origin, and some products of cell damage — and to signal the presence of infections. [ 74 ]
Plant homologs of toll were discovered by Pamela Ronald in 1995 (rice XA21) [ 75 ] and Thomas Boller in 2000 ( Arabidopsis FLS2). [ 76 ]
In 2011, Beutler and Hoffmann were awarded the Nobel Prize in Medicine or Physiology for their work. [ 77 ] Hoffmann and Akira received the Canada Gairdner International Award in 2011. [ 78 ] | https://en.wikipedia.org/wiki/Toll-like_receptor |
Toll Collect GmbH is a German company that has developed and is running the tolling system for trucks ( LKW-Maut ) on German motorways .
The company was a consortium led by Daimler AG , Deutsche Telekom , and Cofiroute until 2018 when it was taken over by German Government. The consortium won a bid for the development of a toll billing system from the German government. The development of the system started in September 2002. The technology is based on the Global Positioning System , and a web application for booking truck routes in advance. Trucks are equipped with embedded systems called "On Board Units" (OBUs). OBUs are used for positioning, monitoring and billing. Additionally, the OBUs have infrared and Dedicated short-range communications (DSRC) interfaces for exchanging data with stationary enforcement gantries and mobile enforcement on the tolled road network.
Since the end of 2002 several hundred engineers and programmers worked on the project. Articles report more than 1000 experts were involved in the project [ citation needed ] . The rollout was first scheduled for the end of August 2003, but was delayed repeatedly, causing the government to forfeit toll collection on trucks using the Autobahn . The deadline was first shifted by 2 months, then by at least one year. Not until the German government purchased Toll Collect were the long-lasting disputes between Toll Collect and the German government about the payment of damages due to the long delay in the launching system resolved. There were also accusations that during the tendering procedure for the system, the offers made by non-German companies were not given fair consideration.
The system was opened two years behind schedule on January 1, 2005. It was the first system in the world that deployed a national GNSS road pricing scheme. The charge per kilometre varies according to the number of axles and the vehicle's emission category, and is between 9 and 14 cents per kilometre. For a trip from Hamburg to Munich (776 km) for example, the costs lie between €69.84 and €108.64. Since the installation of an On Board Unit (OBU) by a professional service is costly and/or time-consuming, the option of paying for a specific trip tickets was also provided from the very beginning (as illustrated).
In publications from December 2019, however, journalists attributed Toll Collect's whereabouts to the federal government to the contracts signed by Transport Minister Andreas Scheuer with industry representatives on the failed car toll in December 2018 and also critically assessed the role of the State Secretary and later Toll Collect boss Gerhard Schulz . According to this, the provision of parts of the Toll Collect infrastructure was probably already assured to Scheuer's contractual partners at the time before the bidding process for the Toll Collect privatization was officially ended in January 2019. [ 1 ]
Generally, for any truck travelling on the German motorways, the distance-based fees can be paid by different means: through the advanced purchase of a specific route via the internet or at payment terminals (typically located in fuel stations), or fully automated through the use of OBUs that are professionally installed in the trucks. Through the use of satellite navigation , the position and the trip are data stored in the OBU which enable the device to determine the tolling fees that apply for the route driven. The data collected in the OBU are transferred to the data center by mobile data communication (GSM), and processed for billing. The fact that the system is "satellite based" relates to the positioning only, not to the communication of the OBU to the data center.
To prevent avoidance of toll payments (e.g. by switching off the OBUs), the trucks are photographed at approximately 300 toll enforcement gantries, and checked by approximately 450 mobile checking stations. The data generated from these compliance checks are compared in the central computing system, and enforcement measured being started. The non-compliance rate is published as being constantly less than 1%. [ 2 ]
Plans to export the specific German solution to other countries were not realized, but a number of GNSS-based tolling solutions were implemented in European countries for distance-based charging of trucks. Plans to expand the system to value-added services, such as fleet management, were not implemented. [ 3 ] | https://en.wikipedia.org/wiki/Toll_Collect |
Road tolling to finance bridges, tunnels and roads has a long history in Norway. The cities Oslo , Bergen and Trondheim introduced toll rings between 1986 and 1991 as a means to discourage urban traffic and to finance infrastructure projects around those cities. [ 1 ] Today toll rings circumscribe Oslo, Kristiansand , Stavanger , Haugesund , Bergen , Askøy , Bodø , Harstad , Grenland , Førde and Trondheim . Besides toll rings, road tolls are installed to finance certain road projects, and often also on the existing road to discourage people from using it. Some tolls use congestion pricing and/or environmentally differentiated toll rates.
There is an ongoing reform of the road toll sector, proposed by Prime minister Solberg's Cabinet . The toll reform has four parts: a reduction of the number of toll road operators, separation of the toll service provision for tolls and ferry tickets from the toll road operators, an interest compensation scheme for toll road loans, and a simplification of the price and discount schemes. [ 2 ]
The Norwegian electronic toll collection system is called AutoPASS , and is administrated by the Norwegian Public Roads Administration . There are no manual toll stations left. The system involves the installation of a DSRC based radio transponder operating at 5.8 GHz (MD5885), originally supplied by the Norwegian companies Q-Free and Fenrits , and since 2013 supplied by Kapsch and Norbit, [ 3 ] [ 4 ] on the windscreen of a vehicle, and to sign a contract with one of the toll service providers. With an AutoPASS contract it is also possible to use the tag in Denmark and Sweden on ferries and bridges through the EasyGo partnership. [ 5 ] [ 6 ]
In December 2021, the Norwegian Public Roads Administration withdrew from EasyGo starting a transition period until 31 March 2022. [ 7 ] Providers need to be EETS-registered and approved by the operators in order for the OBE to be valid in those toll facilities after the transition period ends.
If a vehicle passes through a toll station without a valid transponder, a photograph is taken of the registration number. Norwegian-registered vehicles are invoiced directly by the toll road operators, and foreign vehicles are invoiced by Epass24. [ 9 ] [ 10 ] If a foreign vehicle is driven through a toll that uses environmentally differentiated toll rates, the highest rate will be charged unless the vehicle's Euro class and fuel type are registered. Registration is optional, but registering to the scheme, which is called "Visitors' Payment" will, in addition to the avoidance of paying the highest fee in tolls with environmentally differentiated rates, normally reduce the time from the journey until an invoice is received. The account also gives access to the invoices, the possibility to register for e-mail delivery and to make the payment.
If driving a rental car, the renter should register the car to receive the invoice directly. If it is not registered, the invoice will be sent to the rental company (the car owner). The company may add administration fees when collecting the amount from the renter. [ 11 ]
All vehicles that exceed 3.5 tonnes (3.4 long tons; 3.9 short tons) and are primarily used for business, or are registered to a business, government, county municipality or municipality, must have a valid toll tag/agreement when driving on Norwegian public roads. [ 12 ]
Through the process of Prop. 1 S Appendix 2 / Innst. 13 S (2015-2016), the Storting has endorsed the government's proposal to introduce a new tariff and discount system for tolling projects. In the new system, there will be a standardization of discounts. Vehicles in pricing group 1 with electronic tag and valid agreement will automatically receive 20 per cent discount. Vehicles in rate group 2 will not get a discount. [ 14 ] Discount and other benefits is only given to vehicles with a valid tag/agreement, "Visitors' Payment" does not give the same benefits.
Toll fees for zero-emission vehicles in rate group 1 is introduced in a growing number of tolling projects. Zero-emission vehicle is a collective name for electric cars and hydrogen cars, and the toll fee is maximum 50% of ordinary toll fee after discount (i.e. if the toll fee is 10 NOK, it costs 8 NOK for those with a valid tag/agreement. The toll fee for zero-emission vehicles can hence be maximum 4 NOK). The introduction of payment for zero-emission vehicles is done according to the instructions from Prop. 87 S (2017-2018) and local government. Payment of tolls as a zero-emission vehicle requires tag and a valid agreement. Without a tag and a valid agreement, zero-emission vehicles will be charged ordinary fare like other vehicles. [ 15 ] [ 16 ] [ 17 ] The exception is in tolls that has environmentally differentiated rates (currently the toll rings in Oslo and Akershus and in Bergen). In these, an agreement is only needed to get the general tag discount on top of the (lower) zero-emission price rate. [ 18 ]
A toll road operator, who has signed a toll charge agreement with Statens vegvesen is responsible for the financing of all toll roads in Norway. [ 19 ] As a consequence of the toll reform, regional toll road operators, owned jointly by the counties , have been created:
The following ferry crossings collect road tolls as a surcharge to the ferry ticket: [ 49 ]
Many crossings without toll charges also uses AutoPass as payment through the "AutoPass for ferry" concept. [ 50 ] AutoPass customers with a valid agreement and tag, but without a separate ferry account gets a 10% discount in ferry crossings taking payment with the AutoPass tag. By making a prepayment into an Autopass ferry account, you get a 50% (40% corporate) discount for vehicle, and 17% for passengers at manual payment crossings. | https://en.wikipedia.org/wiki/Toll_roads_in_Norway |
Tollens' reagent (chemical formula Ag ( NH 3 ) 2 OH {\displaystyle {\ce {Ag(NH3)2OH}}} ) is a chemical reagent used to distinguish between aldehydes and ketones along with some alpha-hydroxy ketones which can tautomerize into aldehydes. The reagent consists of a solution of silver nitrate , ammonium hydroxide and some sodium hydroxide (to maintain a basic pH of the reagent solution). It was named after its discoverer, the German chemist Bernhard Tollens . [ 1 ] A positive test with Tollens' reagent is indicated by the precipitation of elemental silver, often producing a characteristic " silver mirror " on the inner surface of the reaction vessel.
This reagent is not commercially available due to its short shelf life , so it must be freshly prepared in the laboratory. One common preparation involves two steps. First a few drops of dilute sodium hydroxide are added to some aqueous 0.1 M silver nitrate . The OH − {\displaystyle {\ce {OH-}}} ions convert the silver aquo complex form into silver(I) oxide , Ag 2 O {\displaystyle {\ce {Ag2O}}} , which precipitates from the solution as a brown solid:
In the next step, sufficient aqueous ammonia is added to dissolve the brown silver(I) oxide. The resulting solution contains the [Ag(NH 3 ) 2 ] + complexes in the mixture, which is the main component of Tollens' reagent. Sodium hydroxide is reformed:
Alternatively, aqueous ammonia can be added directly to silver nitrate solution. [ 2 ] At first, ammonia will induce formation of solid silver oxide, but with additional ammonia, this solid precipitate dissolves to give a clear solution of diamminesilver(I) coordination complex , [ Ag ( NH 3 ) 2 ] + {\displaystyle {\ce {[Ag(NH3)2]+}}} . Filtering the reagent before use helps to prevent false-positive results.
Once the presence of a carbonyl group has been identified using 2,4-dinitrophenylhydrazine (also known as Brady's reagent or 2,4-DNPH or 2,4-DNP), Tollens' reagent can be used to distinguish ketone vs aldehyde . Tollens' reagent gives a negative test for most ketones, with alpha-hydroxy ketones being one exception.
The test rests on the premise that aldehydes are more readily oxidized compared with ketones; this is due to the carbonyl-containing carbon in aldehydes having attached hydrogen. The diamine silver(I) complex in the mixture is an oxidizing agent and is the essential reactant in Tollens' reagent. The test is generally carried out in a test tube in a warm water bath.
In a positive test, the diamine silver(I) complex oxidizes the aldehyde to a carboxylate ion and in the process is reduced to elemental silver and aqueous ammonia. The elemental silver precipitates out of solution, occasionally onto the inner surface of the reaction vessel, giving a characteristic "silver mirror". The carboxylate ion on acidification will give its corresponding carboxylic acid . The carboxylic acid is not directly formed in the first place as the reaction takes place under alkaline conditions. The ionic equations for the overall reaction are shown below; R refers to an alkyl group. [ 3 ]
Tollens' reagent can also be used to test for terminal alkynes ( R − C 2 H {\displaystyle {\ce {R-C2H}}} ). A white precipitate of the acetylide ( AgC 2 − R {\displaystyle {\ce {AgC_2-R}}} ) is formed in this case. Another test relies on reaction of the furfural with phloroglucinol to produce a colored compound with high molar absorptivity. [ 4 ] It also gives a positive test with hydrazines , hydrazones , α-hydroxy ketones and 1,2-dicarbonyls .
Both Tollens' reagent and Fehling's reagent give positive results with formic acid . [ citation needed ]
In anatomic pathology , ammonical silver nitrate is used in the Fontana–Masson stain , which is a silver stain technique used to detect melanin , argentaffin , and lipofuscin in tissue sections. Melanin and the other chromaffins reduce the silver nitrate to metallic silver. [ 2 ]
Tollens' reagent is also used to apply a silver mirror to glassware; for example the inside of an insulated vacuum flask. The underlying chemical process is called silver mirror reaction . The reducing agent is glucose (an aldehyde) for such applications. Clean glassware is required for a high quality mirror. To increase the speed of deposition, the glass surface may be pre-treated with tin(II) chloride stabilised in hydrochloric acid solution. [ 5 ]
For applications requiring the highest optical quality, such as in telescope mirrors , the use of tin(II) chloride is problematic, since it creates nanoscale roughness and reduces the reflectivity. [ 6 ] [ 7 ] Methods to produce telescope mirrors include additional additives to increase adhesion and film resilience, such as in Martin's method, which includes tartaric acid and ethanol . [ 7 ]
Aged reagent can be destroyed with dilute acid to prevent the formation of the highly explosive silver nitride . [ 8 ] | https://en.wikipedia.org/wiki/Tollens'_reagent |
In fluid dynamics , a Tollmien–Schlichting wave (often abbreviated T-S wave ) is a streamwise unstable wave which arises in a bounded shear flow (such as boundary layer and channel flow). It is one of the more common methods by which a laminar bounded shear flow transitions to turbulence . The waves are initiated when some disturbance (sound, for example) interacts with leading edge roughness in a process known as receptivity. These waves are slowly amplified as they move downstream until they may eventually grow large enough that nonlinearities take over and the flow transitions to turbulence.
These waves, originally discovered by Ludwig Prandtl , were further studied by two of his former students, Walter Tollmien and Hermann Schlichting after whom the phenomenon is named.
Also, the T-S wave is defined as the most unstable eigen-mode of Orr–Sommerfeld equations . [ 1 ]
In order for a boundary layer to be absolutely unstable (have an inviscid instability), it must satisfy Rayleigh's criterion; namely
where D {\displaystyle D} represents the y-derivative and U {\displaystyle U} is the free stream velocity profile. In other words, the velocity profile must have an inflection point to be unstable.
It is clear that in a typical boundary layer with a zero pressure gradient, the flow will be unconditionally stable; however, we know from experience this is not the case and the flow does transition. It is clear, then, that viscosity must be an important factor in the instability. It can be shown using energy methods that
The rightmost term is a viscous dissipation term and is stabilizing. The left term, however, is the Reynolds stress term and is the primary production method for instability growth. In an inviscid flow, the u ′ {\displaystyle u'} and v ′ {\displaystyle v'} terms are orthogonal, so the term is zero, as one would expect. However, with the addition of viscosity, the two components are no longer orthogonal and the term becomes nonzero. In this regard, viscosity is destabilizing and is the reason for the formation of T-S waves.
In a laminar boundary layer, if the initial disturbance spectrum is nearly infinitesimal and random (with no discrete frequency peaks), the initial instability will occur as two-dimensional Tollmien–Schlichting waves, travelling in the mean flow direction if compressibility is not important. However, three-dimensionality soon appears as the Tollmien–Schlichting waves rather quickly begin to show variations.
There are known to be many paths from Tollmien–Schlichting waves to turbulence, and many of them are explained by the non-linear theories of flow instability .
A shear layer develops viscous instability and forms Tollmien–Schlichting waves which grow, while still laminar, into finite amplitude (1 to 2 percent of the freestream velocity) three-dimensional fluctuations in velocity and pressure to develop three-dimensional unstable waves and hairpin eddies . From then on, the process is more a breakdown than a growth. The longitudinally stretched vortices begin a cascading breakdown into smaller units, until the relevant frequencies and wave numbers are approaching randomness. Then in this diffusively fluctuating state, intense local changes occur at random times and locations in the shear layer near the wall. At the locally intense fluctuations, turbulent 'spots' are formed that burst forth in the form of growing and spreading spots — the result of which is a fully turbulent state downstream.
Tollmien (1931) [ 2 ] and Schlichting (1929) [ 3 ] theorized that viscosity-induced grabbing and releasing of laminae created long-crested simple harmonic (SH) oscillations (vibrations) along a smooth flat boundary, at a flow rate approaching the onset of turbulence. These T-S waves would gradually increase in amplitude until they broke up into the vortices, noise and high resistance that characterize turbulent flow. Contemporary wind tunnels failed to show T-S waves.
In 1943, Schubauer and Skramstad (S and S) [ 4 ] created a wind tunnel that went to extremes to damp mechanical vibrations and sounds that might affect the airflow studies along a smooth flat plate. Using a vertical array of evenly spaced hot wire anemometers in the boundary layer (BL) airflow, they substantiated the existence of T-S oscillations by showing SH velocity fluctuations in the BL laminae. The T-S waves gradually increased in amplitude until a few random spikes of in-phase amplitude appeared, triggering focal vortices (turbulent spots), with noise. A further increase in flow rate resulted suddenly in many vortices, aerodynamic noise and a great increase in resistance to flow. An oscillation of a mass in a fluid creates a sound wave; SH oscillations of a mass of fluid, flowing in that same fluid along a boundary, must result in SH sound, reflected off the boundary, transversely into the fluid.
S and S found foci of in-phase spiking amplitude in the T-S waves; these must create bursts of high amplitude sound, with high energy oscillation of fluid molecules transversely through the BL laminae. This has the potential to freeze laminar slip (laminar interlocking) in these spots, transferring the resistance to the boundary: this breaking at the boundary could rip out pieces of T-S long-crested waves which would tumble head-over-heels downstream in the boundary layer as the vortices of turbulent spots. With further increase in flow rate, there is an explosion into turbulence, with many random vortices and the noise of aerodynamic sound.
Schubauer and Skramstad overlooked the significance of the co-generation of transverse SH sound by the T-S waves in transition and turbulence. However, John Tyndall (1867) in his transition-to-turbulence flow studies using flames, [ 5 ] deduced that SH waves were created during transition by viscosity acting around the walls of a tube and these could be amplified by blending with similar SH sound waves (from a whistle), triggering turbulence at lower flow rates. Schubauer and Skramstad introduced SH sound into the boundary layer by creating SH fluttering vibrations of a BL ferromagnetic ribbon in their 1941 experiments, similarly triggering turbulence at lower flow rates.
Tyndall’s contribution towards explaining the mystery of transition to turbulence 150 years ago is beginning to gain recognition. [ 6 ] | https://en.wikipedia.org/wiki/Tollmien–Schlichting_wave |
Tolman's rule states that, in certain chemical reactions, the steps involve exclusively intermediates of 18- and 16 electron configuration. The rule is an extension of the 18-electron rule . This rule was proposed by American chemist Chadwick A. Tolman . [ 1 ] However, there are exceptions to Tolman's rule, even for reactions that proceed via 2e − steps, because many reactions involve intermediates with fewer than 16 electrons.
Many examples of homogeneous catalysis involving organometallic complexes involve shuttling of complexes between 16- and 18-electron configurations. 16-electron complexes often form adducts with Lewis bases and, if low-valent, undergo oxidative addition .
Conversely, complexes of 18 electron configuration tend to dissociate ligands or undergo reductive elimination : | https://en.wikipedia.org/wiki/Tolman's_rule |
The Tolman electronic parameter ( TEP ) is a measure of the electron donating or withdrawing ability of a ligand . It is determined by measuring the frequency of the A 1 C-O vibrational mode (ν(CO)) of a (pseudo)-C 3v symmetric complex, [LNi(CO) 3 ] by infrared spectroscopy , where L is the ligand of interest. [LNi(CO) 3 ] was chosen as the model compound because such complexes are readily prepared from tetracarbonylnickel(0) . [ 1 ] [ 2 ] The shift in ν(CO) is used to infer the electronic properties of a ligand, which can aid in understanding its behavior in other complexes. The analysis was introduced by Chadwick A. Tolman .
The A 1 carbonyl band is rarely obscured by other bands in the analyte's infrared spectrum. Carbonyl is a small ligand so steric factors do not complicate the analysis. Upon coordination of CO to a metal, ν(CO) typically decreases from 2143 cm −1 of free CO. This shift can be explained by π backbonding : the metal forms a π bond with the carbonyl ligand by donating electrons through its d orbitals into the empty π* anti-bonding orbitals on CO. This interaction strengthens the metal-carbon bond but also weakens the carbon-oxygen bond, resulting in a lower vibrational frequency. If other ligands increase the density of π electrons on the metal, the C-O bond is weakened and ν(CO) decreases further; conversely, if other ligands compete with CO for π backbonding, ν(CO) increases.
Several other scales have been proposed for the ranking of the donor properties of ligands. The HEP scale ranks ligands on the basis of the 13 C NMR shift of a reference ligand. [ 3 ] Lever's electronic parameter ranking is related to the Ru(II/III) couple. [ 4 ] Another scale evaluated ligands on the basis of the redox couples of [Cr(CO) 5 L] 0/+ . [ 5 ]
In a treatment akin to the TEP analysis, the donor properties of N-heterocyclic carbene (NHC) ligands have been ranked according to IR data recorded on cis-[RhCl(NHC)(CO) 2 ] complexes. [ 6 ] [ 7 ] | https://en.wikipedia.org/wiki/Tolman_electronic_parameter |
The Tolman length δ {\displaystyle \delta } (also known as Tolman's delta ) measures the extent by which the surface tension of a small liquid drop deviates from its planar value. It is conveniently defined in terms of an expansion in 1 / R {\displaystyle 1/R} , with R = R e {\displaystyle R=R_{e}} the equimolar radius (defined below) of the liquid drop, of the pressure difference across the droplet's surface:
In this expression, Δ p = p l − p v {\displaystyle \Delta p=p_{l}-p_{v}} is the pressure difference between the (bulk) pressure of the liquid inside and the pressure of the vapour outside, and σ {\displaystyle \sigma } is the surface tension of the planar interface , i.e. the interface with zero curvature R = ∞ {\displaystyle R=\infty } . The Tolman length δ {\displaystyle \delta } is thus defined as the leading order correction in an expansion in 1 / R {\displaystyle 1/R} .
The equimolar radius is defined so that the superficial density is zero, i.e., it is defined by imagining a sharp mathematical dividing surface with a uniform internal and external density, but where the total mass of the pure fluid is exactly equal to the real situation. At the atomic scale in a real drop, the surface is not sharp, rather the density gradually drops to zero, and the Tolman length captures the fact that the idealized equimolar surface does not necessarily coincide with the idealized tension surface.
Another way to define the Tolman length is to consider the radius dependence of the surface tension, σ ( R ) {\displaystyle \sigma (R)} . To leading order in 1 / R {\displaystyle 1/R} one has:
Here σ ( R ) {\displaystyle \sigma (R)} denotes the surface tension (or (excess) surface free energy) of a liquid drop with radius R {\displaystyle R} , whereas σ {\displaystyle \sigma } denotes its value in the planar limit.
In both definitions (1) and (2) the Tolman length is defined as a coefficient in an expansion in 1 / R {\displaystyle 1/R} and therefore does not depend on R {\displaystyle R} .
Furthermore, the Tolman length can be related to the radius of spontaneous curvature when one compares the free energy method of Helfrich with the method of Tolman:
Any result for the Tolman length therefore gives information about the radius of spontaneous curvature, R 0 {\displaystyle R_{0}} . If the Tolman length is known to be positive (with k > 0 {\displaystyle k>0} ) the interface tends to curve towards the liquid phase, whereas a negative Tolman length implies a negative R 0 {\displaystyle R_{0}} and a preferred curvature towards the vapour phase.
Apart from being related to the radius of spontaneous curvature, the Tolman length can be linked to the surface of tension . The surface of tension, positioned at R = R s {\displaystyle R=R_{s}} , is defined as the surface for which the Young-Laplace equation holds exactly for all droplet radii:
where σ s = σ ( R = R s ) {\displaystyle \sigma _{s}=\sigma (R=R_{s})} is the surface tension at the surface of tension. Using the Gibbs adsorption equation , Tolman himself showed that the Tolman length can be expressed in terms of the adsorbed amount at the surface of tension at coexistence
where Δ ρ 0 = ρ l , 0 − ρ v , 0 {\displaystyle \Delta \rho _{0}=\rho _{l,0}-\rho _{v,0}} ; the subscript zero to the density denotes the value at two-phase coexistence. It can be shown that the difference between the location of the surface of tension and of the equimolar dividing surface proposed by Gibbs yields the value of the Tolman length:
where the z e , z s {\displaystyle z_{e},z_{s}} denote the locations of the corresponding surfaces making the magnitude of the Tolman length in the order of nanometers. | https://en.wikipedia.org/wiki/Tolman_length |
In astrophysics , the Tolman–Oppenheimer–Volkoff ( TOV ) equation constrains the structure of a spherically symmetric body of isotropic material which is in static gravitational equilibrium, as modeled by general relativity . The equation [ 1 ] is
Here, r {\textstyle r} is a radial coordinate, and ρ ( r ) {\textstyle \rho (r)} and P ( r ) {\textstyle P(r)} are the density and pressure, respectively, of the material at radius r {\textstyle r} . The quantity m ( r ) {\textstyle m(r)} , the total mass within r {\textstyle r} , is discussed below.
The equation is derived by solving the Einstein equations for a general time-invariant, spherically symmetric metric. For a solution to the Tolman–Oppenheimer–Volkoff equation, this metric will take the form [ 1 ]
where ν ( r ) {\textstyle \nu (r)} is determined by the constraint [ 1 ]
When supplemented with an equation of state , F ( ρ , P ) = 0 {\textstyle F(\rho ,P)=0} , which relates density to pressure, the Tolman–Oppenheimer–Volkoff equation completely determines the structure of a spherically symmetric body of isotropic material in equilibrium. If terms of order 1 / c 2 {\textstyle 1/c^{2}} are neglected, the Tolman–Oppenheimer–Volkoff equation becomes the Newtonian hydrostatic equation , used to find the equilibrium structure of a spherically symmetric body of isotropic material when general-relativistic corrections are not important.
If the equation is used to model a bounded sphere of material in a vacuum, the zero-pressure condition P ( r ) = 0 {\textstyle P(r)=0} and the condition e ν = 1 − 2 G m / c 2 r {\textstyle e^{\nu }=1-2Gm/c^{2}r} should be imposed at the boundary. The second boundary condition is imposed so that the metric at the boundary is continuous with the unique static spherically symmetric solution to the vacuum field equations , the Schwarzschild metric :
m ( r ) {\textstyle m(r)} is the total mass contained inside radius r {\textstyle r} , as measured by the gravitational field felt by a distant observer. It satisfies m ( 0 ) = 0 {\textstyle m(0)=0} . [ 1 ]
Here, M {\textstyle M} is the total mass of the object, again, as measured by the gravitational field felt by a distant observer. If the boundary is at r = R {\textstyle r=R} , continuity of the metric and the definition of m ( r ) {\textstyle m(r)} require that
Computing the mass by integrating the density of the object over its volume, on the other hand, will yield the larger value
The difference between these two quantities,
will be the gravitational binding energy of the object divided by c 2 {\textstyle c^{2}} and it is negative.
Let us assume a static, spherically symmetric perfect fluid. The metric components are similar to those for the Schwarzschild metric : [ 2 ]
By the perfect fluid assumption, the stress-energy tensor is diagonal (in the central spherical coordinate system), with eigenvalues of energy density and pressure:
and
Where ρ ( r ) {\textstyle \rho (r)} is the fluid density and P ( r ) {\textstyle P(r)} is the fluid pressure.
To proceed further, we solve Einstein's field equations:
Let us first consider the G 00 {\textstyle G_{00}} component:
Integrating this expression from 0 to r {\textstyle r} , we obtain
where m ( r ) {\textstyle m(r)} is as defined in the previous section.
Next, consider the G 11 {\textstyle G_{11}} component. Explicitly, we have
which we can simplify (using our expression for e λ {\textstyle e^{\lambda }} ) to
We obtain a second equation by demanding continuity of the stress-energy tensor: ∇ μ T ν μ = 0 {\textstyle \nabla _{\mu }T_{\,\nu }^{\mu }=0} . Observing that ∂ t ρ = ∂ t P = 0 {\textstyle \partial _{t}\rho =\partial _{t}P=0} (since the configuration is assumed to be static) and that ∂ ϕ P = ∂ θ P = 0 {\textstyle \partial _{\phi }P=\partial _{\theta }P=0} (since the configuration is also isotropic), we obtain in particular
Rearranging terms yields: [ 3 ]
This gives us two expressions, both containing d ν / d r {\textstyle d\nu /dr} . Eliminating d ν / d r {\textstyle d\nu /dr} , we obtain:
Pulling out a factor of G / r {\textstyle G/r} and rearranging factors of 2 and c 2 {\textstyle c^{2}} results in the Tolman–Oppenheimer–Volkoff equation:
Richard C. Tolman analyzed spherically symmetric metrics in 1934 and 1939. [ 4 ] [ 5 ] The form of the equation given here was derived by J. Robert Oppenheimer and George Volkoff in their 1939 paper, "On Massive Neutron Cores". [ 1 ] In this paper, the equation of state for a degenerate Fermi gas of neutrons was used to calculate an upper limit of ~0.7 solar masses for the gravitational mass of a neutron star . Since this equation of state is not realistic for a neutron star, this limiting mass is likewise incorrect. Using gravitational wave observations from binary neutron star mergers (like GW170817 ) and the subsequent information from electromagnetic radiation ( kilonova ), the data suggest that the maximum mass limit is close to 2.17 solar masses . [ 6 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ] Earlier estimates for this limit range from 1.5 to 3.0 solar masses. [ 11 ]
In the post-Newtonian approximation , i.e., gravitational fields that slightly deviates from Newtonian field , the equation can be expanded in powers of 1 / c 2 {\textstyle 1/c^{2}} . In other words, we have | https://en.wikipedia.org/wiki/Tolman–Oppenheimer–Volkoff_equation |
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