Overview.

Particles tend to move from higher chemical potential to lower chemical potential. In this way, chemical potential is a generalization of "potentials" in physics such as gravitational potential. When a ball rolls down a hill, it is moving from a higher gravitational potential (higher internal energy thus higher potential for work) to a lower gravitational potential (lower internal energy). In the same way, as molecules move, react, dissolve, melt, etc., they will always tend naturally to go from a higher chemical potential to a lower one, changing the particle number, which is conjugate variable to chemical potential.  A simple example is a system of dilute molecules diffusing in a homogeneous environment. In this system, the molecules tend to move from areas with high concentration to low concentration, until eventually, the concentration is the same everywhere.  The microscopic explanation for this is based in kinetic theory and the random motion of molecules. However, it is simpler to describe the process in terms of chemical potentials: For a given temperature, a molecule has a higher chemical potential in a higher-concentration area and a lower chemical potential in a low concentration area. Movement of molecules from higher chemical potential to lower chemical potential is accompanied by a release of free energy. Therefore, it is a spontaneous process.  Another example, not based on concentration but on phase, is a glass of liquid water with ice cubes in it. Above 0 °C, an HO molecule that is in the liquid phase (liquid water) has a lower chemical potential than a water molecule that is in the solid phase (ice). When some of the ice melts, HO molecules convert from solid to liquid where their chemical potential is lower, so the ice cubes shrink. Below 0 °C, the molecules in the ice phase have the lower chemical potential, so the ice cubes grow. At the temperature of the melting point, 0 °C, the chemical potentials in water and ice are the same; the ice cubes neither grow nor shrink, and the system is in equilibrium.  A third example is illustrated by the chemical reaction of dissociation of a weak acid HA (such as acetic acid, A = CHCOO): Vinegar contains acetic acid. When acid molecules dissociate, the concentration of the undissociated acid molecules (HA) decreases and the concentrations of the product ions (H and A) increase. Thus the chemical potential of HA decreases and the sum of the chemical potentials of H and A increases. When the sums of chemical potential of reactants and products are equal the system is at equilibrium and there is no tendency for the reaction to proceed in either the forward or backward direction. This explains why vinegar is acidic, because acetic acid dissociates to some extent, releasing hydrogen ions into the solution.  Chemical potentials are important in many aspects of equilibrium chemistry, including melting, boiling, evaporation, solubility, osmosis, partition coefficient, liquid-liquid extraction and chromatography. In each case there is a characteristic constant which is a function of the chemical potentials of the species at equilibrium.  In electrochemistry, ions do "not" always tend to go from higher to lower chemical potential, but they "do" always go from higher to lower "electrochemical potential". The electrochemical potential completely characterizes all of the influences on an ion's motion, while the chemical potential includes everything "except" the electric force. (See below for more on this terminology.)

Thermodynamic definition.

The chemical potential "μ" of species "i" (atomic, molecular or nuclear) is defined, as all intensive quantities are, by the phenomenological fundamental equation of thermodynamics expressed in the form, which holds for both reversible and irreversible processes:  where d"U" is the infinitesimal change of internal energy "U", d"S" the infinitesimal change of entropy "S", and d"V" is the infinitesimal change of volume "V" for a thermodynamic system in thermal equilibrium, and d"N" is the infinitesimal change of particle number "N" of species "i" as particles are added or subtracted. "T" is absolute temperature, "S" is entropy, "P" is pressure, and "V" is volume. Other work terms, such as those involving electric, magnetic or gravitational fields may be added.  From the above equation, the chemical potential is given by  This is an inconvenient expression for condensed-matter systems, such as chemical solutions, as it is hard to control the volume and entropy to be constant while particles are added. A more convenient expression may be obtained by making a Legendre transformation to another thermodynamic potential: the Gibbs free energy formula_4. From the differential formula_5 and using the above expression for formula_6, a differential relation for formula_7 is obtained:  As a consequence, another expression for formula_9 results:  and the change in Gibbs free energy of a system that is held at constant temperature and pressure is simply  In thermodynamic equilibrium, when the system concerned is at constant temperature and pressure but can exchange particles with its external environment, the Gibbs free energy is at its minimum for the system, that is formula_12. It follows that  Use of this equality provides the means to establish the equilibrium constant for a chemical reaction.  By making further Legendre transformations from "U" to other thermodynamic potentials like the enthalpy formula_14 and Helmholtz free energy formula_15, expressions for the chemical potential may be obtained in terms of these:  These different forms for the chemical potential are all equivalent, meaning that they have the same physical content and may be useful in different physical situations.

Applications.

The Gibbs–Duhem equation is useful because it relates individual chemical potentials. For example, in a binary mixture, at constant temperature and pressure, the chemical potentials of the two participants are related by  Every instance of phase or chemical equilibrium is characterized by a constant. For instance, the melting of ice is characterized by a temperature, known as the melting point at which solid and liquid phases are in equilibrium with each other. Chemical potentials can be used to explain the slopes of lines on a phase diagram by using the Clapeyron equation, which in turn can be derived from the Gibbs–Duhem equation. They are used to explain colligative properties such as melting-point depression by the application of pressure. Both Raoult's law and Henry's law can be derived in a simple manner using chemical potentials.

History.

Chemical potential was first described by the American engineer, chemist and mathematical physicist Josiah Willard Gibbs. He defined it as follows:  Gibbs later noted also that for the purposes of this definition, any chemical element or combination of elements in given proportions may be considered a substance, whether capable or not of existing by itself as a homogeneous body. This freedom to choose the boundary of the system allows the chemical potential to be applied to a huge range of systems. The term can be used in thermodynamics and physics for any system undergoing change. Chemical potential is also referred to as partial molar Gibbs energy (see also partial molar property). Chemical potential is measured in units of energy/particle or, equivalently, energy/mole.  In his 1873 paper "A Method of Geometrical Representation of the Thermodynamic Properties of Substances by Means of Surfaces", Gibbs introduced the preliminary outline of the principles of his new equation able to predict or estimate the tendencies of various natural processes to ensue when bodies or systems are brought into contact. By studying the interactions of homogeneous substances in contact, i.e. bodies, being in composition part solid, part liquid, and part vapor, and by using a three-dimensional volume–entropy–internal energy graph, Gibbs was able to determine three states of equilibrium, i.e. "necessarily stable", "neutral", and "unstable", and whether or not changes will ensue. In 1876, Gibbs built on this framework by introducing the concept of chemical potential so to take into account chemical reactions and states of bodies that are chemically different from each other. In his own words, to summarize his results in 1873, Gibbs states: In this description, as used by Gibbs, "ε" refers to the internal energy of the body, "η" refers to the entropy of the body, and "ν" is the volume of the body.

Electrochemical, internal, external, and total chemical potential.

The abstract definition of chemical potential given above—total change in free energy per extra mole of substance—is more specifically called total chemical potential. If two locations have different total chemical potentials for a species, some of it may be due to potentials associated with "external" force fields (Electric potential energy differences, gravitational potential energy differences, etc.), while the rest would be due to "internal" factors (density, temperature, etc.) Therefore, the total chemical potential can be split into internal chemical potential and external chemical potential: where i.e., the external potential is the sum of electric potential, gravitational potential, etc. ("q" and "m" are the charge and mass of the species, "V" and "h" are the voltage and height of the container, and "g" is the acceleration due to gravity). The internal chemical potential includes everything else besides the external potentials, such as density, temperature, and enthalpy. This formalism can be understood by assuming that the total energy of a system, formula_21, is the sum of two parts: an internal energy, formula_22, and an external energy due to the interaction of each particle with an external field, formula_23. The definition of chemical potential applied to formula_24 yields the above expression for formula_25.  The phrase "chemical potential" sometimes means "total chemical potential", but that is not universal. In some fields, in particular electrochemistry, semiconductor physics, and solid-state physics, the term "chemical potential" means "internal" chemical potential, while the term electrochemical potential is used to mean "total" chemical potential.

Systems of particles.

Electrons in solids.

Electrons in solids have a chemical potential, defined the same way as the chemical potential of a chemical species: The change in free energy when electrons are added or removed from the system. In the case of electrons, the chemical potential is usually expressed in energy per particle rather than energy per mole, and the energy per particle is conventionally given in units of electronvolt (eV).  Chemical potential plays an especially important role in solid-state physics and is closely related to the concepts of work function, Fermi energy, and Fermi level. For example, n-type silicon has a higher internal chemical potential of electrons than p-type silicon. In a p–n junction diode at equilibrium the chemical potential ("internal" chemical potential) varies from the p-type to the n-type side, while the total chemical potential (electrochemical potential, or, Fermi level) is constant throughout the diode.  As described above, when describing chemical potential, one has to say "relative to what". In the case of electrons in semiconductors, internal chemical potential is often specified relative to some convenient point in the band structure, e.g., to the bottom of the conduction band. It may also be specified "relative to vacuum", to yield a quantity known as work function, however, work function varies from surface to surface even on a completely homogeneous material. Total chemical potential, on the other hand, is usually specified relative to electrical ground.  In atomic physics, the chemical potential of the electrons in an atom is sometimes said to be the negative of the atom's electronegativity. Likewise, the process of chemical potential equalization is sometimes referred to as the process of electronegativity equalization. This connection comes from the Mulliken electronegativity scale. By inserting the energetic definitions of the ionization potential and electron affinity into the Mulliken electronegativity, it is seen that the Mulliken chemical potential is a finite difference approximation of the electronic energy with respect to the number of electrons., i.e.,

Sub-nuclear particles.

In recent years, thermal physics has applied the definition of chemical potential to systems in particle physics and its associated processes. For example, in a quark–gluon plasma or other QCD matter, at every point in space there is a chemical potential for photons, a chemical potential for electrons, a chemical potential for baryon number, electric charge, and so forth.  In the case of photons, photons are bosons and can very easily and rapidly appear or disappear. Therefore, the chemical potential of photons is always and everywhere zero. The reason is, if the chemical potential somewhere was higher than zero, photons would spontaneously disappear from that area until the chemical potential went back to zero; likewise, if the chemical potential somewhere was less than zero, photons would spontaneously appear until the chemical potential went back to zero. Since this process occurs extremely rapidly (at least, it occurs rapidly in the presence of dense charged matter), it is safe to assume that the photon chemical potential is never different from zero.  Electric charge is different because it is conserved, i.e. it can be neither created nor destroyed. It can, however, diffuse. The "chemical potential of electric charge" controls this diffusion: Electric charge, like anything else, will tend to diffuse from areas of higher chemical potential to areas of lower chemical potential. Other conserved quantities like baryon number are the same. In fact, each conserved quantity is associated with a chemical potential and a corresponding tendency to diffuse to equalize it out.  In the case of electrons, the behaviour depends on temperature and context. At low temperatures, with no positrons present, electrons cannot be created or destroyed. Therefore, there is an electron chemical potential that might vary in space, causing diffusion. At very high temperatures, however, electrons and positrons can spontaneously appear out of the vacuum (pair production), so the chemical potential of electrons by themselves becomes a less useful quantity than the chemical potential of the conserved quantities like (electrons minus positrons).  The chemical potentials of bosons and fermions is related to the number of particles and the temperature by Bose–Einstein statistics and Fermi–Dirac statistics respectively.

Ideal vs. non-ideal solutions.

Generally the chemical potential is given as a sum of an ideal contribution and an excess contribution:  In an ideal solution, the chemical potential of species "i" (μ) is dependent on temperature and pressure. μ("T", "P") is defined as the chemical potential of pure species "i". Given this definition, the chemical potential of species "i" in an ideal solution is  where "R" is the gas constant, and formula_29 is the mole fraction of species "i" contained in the solution. Note that the approximation is only valid for formula_29 not approaching zero.  This equation assumes that formula_9 only depends on the mole fraction (formula_29) contained in the solution. This neglects intermolecular interaction between species "i" with itself and other species ["i"–("j"≠"i")]. This can be corrected for by factoring in the coefficient of activity of species "i", defined as γ. This correction yields  The plots above give a rough picture of the ideal and non-ideal situation.

In thermodynamics, chemical potential of a species is energy that can be absorbed or released due to a change of the particle number of the given species, e.g. in a chemical reaction or phase transition. The chemical potential of a species in a mixture is defined as the rate of change of free energy of a thermodynamic system with respect to the change in the number of atoms or molecules of the species that are added to the system. Thus, it is the partial derivative of the free energy with respect to the amount of the species, all other species' concentrations in the mixture remaining constant. The molar chemical potential is also known as partial molar free energy. When both temperature and pressure are held constant, chemical potential is the partial molar Gibbs free energy. At chemical equilibrium or in phase equilibrium the total sum of the product of chemical potentials and stoichiometric coefficients is zero, as the free energy is at a minimum.

在热力学中,某种物质的化学势指的是,在化学反应或者相变中,此物质的粒子数发生改变时所吸收或放出的能量。在混合物中的某种物质的化学势定义为此热力学系统的吉布斯自由能对此物质粒子数的变化率,即偏导数(其他物质的粒子数及其他系统参数保持不变)。当温度和压强固定时,化学势也被称作偏摩尔吉布斯自由能,或者摩尔化学势。在化学平衡或相平衡状态下,自由能处于极小值,各种物质的化学势与化学计量系数乘积之加和为零。


Etymology.

The etymology of "Chittagong" is uncertain. One explanation credits the first Arab traders for "shatt ghangh" () where "shatt" means "delta" and "ghangh" stood for the Ganges. The Arakanese chronicle that a king named Tsu-la-taing Tsandaya, after conquering Bengal, set up a stone pillar as a trophy/memorial at the place since called "Tst-ta-gaung" as the limit of conquest. This Arakanese king ascended the throne in Arakan year 311 corresponding to 952 A.D. He conquered this place two years later. This stone pillar with the inscription "Tset-ta-gaung" meaning 'to make war is improper' cannot be a myth. Another legend

Name.

In 2018, Bangladesh Prime Minister Sheikh Hasina decided to change the city's name to a version

History.

Stone Age fossils and tools unearthed in the region indicate that Chittagong has been inhabited since Neolithic times. It is an ancient port city, with a recorded history dating back to the 4th century BC. Its harbour was mentioned in Ptolemy's world map in the 2nd century as one of the most impressive ports in the East. The region was part of the ancient Bengali Samatata and Harikela kingdoms. The Candra dynasty once dominated the area, and was followed by the Varman dynasty and Deva dynasty.  Chinese traveler Xuanzang described the area as "a sleeping beauty rising from mist and water" in the 7th century.  Arab Muslim traders frequented Chittagong from the 9th century. In 1154, Al-Idrisi wrote of a busy shipping route between Basra and Chittagong, connecting it with the Abbasid capital of Baghdad.  Many Sufi missionaries settled in Chittagong and played an instrumental role in the spread of Islam.  Sultan Fakhruddin Mubarak Shah of Sonargaon conquered Chittagong in 1340, making it a part of Sultanate of Bengal. It was the principal maritime gateway to the kingdom, which was reputed as one of the wealthiest states in the Indian subcontinent. Medieval Chittagong was a hub for maritime trade with China, Sumatra, the Maldives, Sri Lanka, the Middle East and East Africa. It was notable for its medieval trades in pearls, silk, muslin, rice, bullion, horses and gunpowder. The port was also a major shipbuilding hub.  Ibn Battuta visited the port city in 1345. Niccolò de' Conti, from Venice, also visited around the same time as Battuta. Chinese admiral Zheng He's treasure fleet anchored in Chittagong during imperial missions to the Sultanate of Bengal.  Chittagong featured prominently in the military history of the Bengal Sultanate, including during the Reconquest of Arakan and the Bengal Sultanate–Kingdom of Mrauk U War of 1512–1516.  During the 13th and 16th centuries, Arabs and Persians heavily colonized the port city of Chittagong, initially arriving for trade and to preach the word of Islam. Most Arab settlers arrived from the trade route between Iraq and Chittagong, and were perhaps the prime reason for the spread of Islam to Bangladesh. The first Persian settlers have also hinted to arrive for trade and religious purposes, with clues of Persianization tasks as well. Persians and other Iranic peoples have deeply affected the history of the Bengal Sultanate, with Persian being one of the main languages of the Muslim state, as well as also influencing the Chittagonian language and writing scripts. It has been affirmed that much of the Muslim population in Chittagong are descendants of the Arab and Persian settlers.  Two decades after Vasco Da Gama's landing in Calicut, the Bengal Sultanate gave permission for the Portuguese settlement in Chittagong to be established in 1528. It became the first European colonial enclave in Bengal. The Bengal Sultanate lost control of Chittagong in 1531 after Arakan declared independence and the established Kingdom of Mrauk U. This altered geopolitical landscape allowed the Portuguese unhindered control of Chittagong for over a century.  Portuguese ships from Goa and Malacca began frequenting the port city in the 16th century. The "cartaz" system was introduced and required all ships in the area to purchase naval trading licenses from the Portuguese settlement. Slave trade and piracy flourished. The nearby island of Sandwip was conquered in 1602. In 1615, the Portuguese Navy defeated a joint Dutch East India Company and Arakanese fleet near the coast of Chittagong.  In 1666, the Mughal government of Bengal led by viceroy Shaista Khan moved to retake Chittagong from Portuguese and Arakanese control. They launched the Mughal conquest of Chittagong. The Mughals attacked the Arakanese from the jungle with a 6,500-strong army, which was further supported by 288 Mughal naval ships blockading the Chittagong harbour. After three days of battle, the Arakanese surrendered. The Mughals expelled the Portuguese from Chittagong. Mughal rule ushered a new era

Geography.

Topography.

Chittagong lies at. It straddles the coastal foothills of the Chittagong Hill Tracts in southeastern Bangladesh. The Karnaphuli River runs along the southern banks of the city, including its central business district. The river enters the Bay of

Ecological hinterland.

The Chittagong Division is known for its rich biodiversity. Over 2000 of Bangladesh's 6000 flowering plants grow in the region. Its hills and jungles are laden with waterfalls, fast flowing river streams and elephant reserves. St. Martin's Island, within the Chittagong Division, is the only coral island in

Climate.

Under the Köppen climate classification, Chittagong has a tropical monsoon climate (Am).  Chittagong is vulnerable to North

Government.

The Chittagong City Corporation (CCC) is responsible for governing municipal areas in the Chittagong Metropolitan Area. It is headed by the Mayor of Chittagong. The mayor and ward councillors are elected every five years. The mayor is Awami League leader A. J. M. Nasiuruddin, as of May 2015. The city corporation's mandate is limited to basic civic services, however, the CCC is credited for keeping Chittagong one of the cleaner and most eco-friendly cities in Bangladesh. Its principal sources of revenue are municipal taxes and conservancy charges. The Chittagong Development Authority is responsible for implementing the city's urban planning.  Deputy Commissioner and District Magistrate is the head of local administration on behalf of the Government of Bangladesh. Law enforcement is provided by the Chittagong Metropolitan Police and the Rapid Action Battalion-7. The District and Sessions Judge is the head of the local judiciary on behalf of the Supreme Court of Bangladesh. The Divisional Special Judge's Court is located in the colonial-era Chittagong Court Building.  Although all resident embassies and high commissions in Bangladesh are located in capital Dhaka, Chittagong hosts an assistant high commission of India and a consulate general of Russia.

Military.

Chittagong is also a strategically important military port on the Bay of Bengal. The Chittagong Naval Area is the principal base of the Bangladesh Navy and the home port of most Bangladeshi warships. The Bangladesh Naval Academy and the navy's

Economy.

A substantial share of Bangladesh's national GDP is attributed to Chittagong. The City generated approximately $25.5 billion in nominal (2014) and US$67.26 billion in PPP terms converted from nominal GDP of $25.5 Billion dollars with a nominal vs. PPP factor of 2.638. contributing around 12% of the nation's economy. Chittagong generates for 40% of Bangladesh's industrial output, 80% of its international trade and 50% of its governmental revenue. The Chittagong Stock Exchange has more than 700 listed companies, with a market capitalisation of US$32 billion in June 2015. The city is home to many of the country's oldest and largest corporations. The Port of Chittagong handled US$60 billion in annual trade in 2011, ranking 3rd in South Asia after the Port of Mumbai and the Port of Colombo.  The Agrabad area is the main central business district of the city. Major Bangladeshi conglomerates headquartered in Chittagong include M. M. Ispahani Limited,

Culture.

An inhabitant of Chittagong is called "Chittagonian" in English. For centuries, the port city has been a melting pot for people from all over the world. Its historic trade networks have left a lasting impact on its language, culture and cuisine. The Chittagonian language has many Arabic, Persian, English and Portuguese loanwords. The immensely popular traditional feast of "Mezban" features the serving of hot beef dish with white rice. The cultivation of pink pearls is a historic activity in Chittagong. Its Mughal-era name, "Islamabad" (City of Islam), continues to be used in the old city. The name was given due to the port city's history as a gateway for early Islamic missionaries in Bengal. Notable Islamic architecture in Chittagong can be seen in the historic Bengal Sultanate-era Hammadyar Mosque and the Mughal fort of Anderkilla. Chittagong is known as the "Land of the Twelve Saints"

Demographics.

Chittagong has a population of more than 2.5 million, and its Metropolitan Area has a population of 4,009,423. By gender, the population was 54.36% male and 45.64% female, and the literacy rate in the city was 60 percent, in 2002. Muslims at 86% form the overwhelming majority of the population and rest being 12% Hindus and 2% other religions.  Chittagong was a melting pot of ethnicities during the Bengal Sultanate and Mughal Bengal periods. Muslim immigration started as early as seventh century, and significant Muslim settlements occurred during medieval period. Muslim traders, rulers and preachers from Persia and Arabs were the early Muslim settlers, and descendants of them are the majority of current Muslim population of the city. The city has a relatively wealthy and economically influential Shia Muslim

Media and communications.

There are various newspapers, including daily newspapers, opposition newspapers and business newspapers, based in Chittagong. Daily newspapers include Dainik Azadi, Peoples View, The Daily Suprobhat Bangladesh, Purbokon, Life, Karnafuli, Jyoti, Rashtrobarta and Azan. Furthermore, there are a number of weekly and monthly newspapers. These include weeklies such as Chattala, Jyoti, Sultan, Chattagram Darpan and the monthlies such as Sanshodhani, Purobi, Mukulika and Simanto. The only press council in Chittagong is the Chittagong Press Club. Government

Utilities.

The southern zone of the Bangladesh Power Development Board is responsible for supplying electricity to city dwellers. The fire services are provided by the Bangladesh Fire Service & Civil Defence department, under the Ministry of Home Affairs.  The water supply and sewage systems are managed by the Chittagong Water Supply and Sewerage Authority (Chittagong

Education.

The education system of Chittagong is similar to that of rest of Bangladesh, with four main forms of schooling. The general education system, conveyed in both Bangla and English versions, follows the curriculum prepared by the National Curriculum and Textbook Board, part of the Ministry of Education. Students are required to take four major board examinations: the Primary School Certificate (PSC), the Junior School Certificate (JSC), the Secondary School Certificate (SSC) and the Higher Secondary School Certificate (HSC) before moving onto higher education. The Board of Intermediate and Secondary Education, Chittagong is responsible for administering SSC and HSC examinations within the city. The Madrasah education system is primarily based on Islamic studies, though other subjects are also taught. Students are prepared according to the Dakhil and Alim examinations, which are controlled by the Bangladesh Madrasah Education Board and are equivalent to SSC and HSC examinations of the general education system respectively. There are also several private schools in the city, usually referred to as "English medium schools", which follow the General Certificate

Health.

The Chittagong Medical College Hospital is the largest state-owned hospital in Chittagong. The Chittagong General Hospital, established in 1901, is the oldest hospital in the city. The Bangladesh Institute of Tropical and Infectious Diseases (BITID)

Transport.

Transport in Chittagong is similar to that of the capital, Dhaka. Large avenues and roads are present throughout the metropolis. There are various bus systems and taxi services, as well as smaller 'baby' or 'CNG' taxis, which are tricycle-structured motor vehicles. Foreign and local ridesharing companies like Uber and Pathao are operating in the city. There are also traditional manual rickshaws, which are very common.

Road.

As the population of the city has begun to grow extensively, the Chittagong Development Authority (CDA) has undertaken some transportation initiatives aimed at easing the traffic congestion in Chittagong. Under this plan, the CDA, along with the Chittagong City Corporation, have constructed some flyovers and expanded the existing roads within the city. There are also some other major expressways and flyovers under-construction, most notably the Chittagong City Outer Ring Road, which runs along the coast of Chittagong city. This ring road includes a marine drive along

Rail.

Chittagong can also be accessed by rail. It has a station on the metre gauge, eastern section of the Bangladesh Railway, whose headquarters are also located within the city. There are two main railway stations, on Station Road and in the Pahartali Thana.

Air.

The Shah Amanat International Airport, located at South Patenga, serves as Chittagong's only airport. It is the second busiest airport in Bangladesh. The airport is capable of annually handling 1.5 million passengers and 6,000 tonnes of cargo. Known as "Chittagong Airfield" during World War II, the airport was used as a combat airfield, as well as a supply point and photographic reconnaissance base by the United

Sports.

Chittagong has produced numerous cricketers, footballers and athletes, who have performed at the national level. Tamim Iqbal, Akram Khan, Minhajul Abedin, Aftab Ahmed, Nafees Iqbal, Nazimuddin, Faisal Hossain, Tareq Aziz, Mominul Haque, Irfan Sukkur, Yasir Ali Chowdhury, Nayeem Hasan, Minhajul Abedin Afridi are some of the most prominent figures among them. Cricket is the most popular sport in Chittagong, while football, tennis and kabaddi are also popular. A number of stadiums are located in Chittagong with the main one being the multipurpose MA Aziz Stadium, which has a seating capacity of 20,000 and hosts football matches in addition

Twin towns and sister cities.

Chittagong is twinned with:

Chittagong (), officially known as Chattogram () and also known as the Port City of Bangladesh, is a major coastal city and financial centre in southeastern Bangladesh. The city has a population of more than 2.5 million while the metropolitan area had a population of 4,009,423 in 2011, making it the second-largest city in the country. It is the capital of an eponymous District and Division. The city is located on the banks of the Karnaphuli River between the Chittagong Hill Tracts and the Bay of Bengal. Modern Chittagong is Bangladesh's second most significant urban center after Dhaka.

吉大港(孟加拉语:)是孟加拉国第二大城市以及第一大港,吉大港区的首府,人口5,658,560人(2020年),还在不断增长,临孟加拉湾,位在戈尔诺普利河右岸。吉大港是孟加拉的重要交通枢钮和工业中心,工业有炼油、造船、钢铁、纺织、玻璃及食品加工等,而其拆船回收业格外出名,该拆船厂区供应了本国75%金属来源。它位于孟加拉国的东南部,周围被丘陵环绕。吉大港山区位于附近。


Geography.

Location.

The municipality lies in the Hunsrück roughly 8 km southwest of Kirchberg and 16 km southwest of Simmern.

History.

Prehistory and antiquity.

Going by archaeological finds from prehistory and protohistory, the Laufersweiler area might have been settled as early as the Bronze Age and Hallstatt times. Along what is now the municipal limit between Laufersweiler and Niederweiler ran the "Via Ausonia" (or "Ausoniusstraße" in German) in Roman times. This led from Trier to Bingen am Rhein. Archaeological finds bear witness to a settlement in Roman times.

Middle Ages.

In 1283, Laufersweiler had its first documentary mention as "Leuferswilre", and was owned by the Waldgraves. In the 14th century, the ownership arrangements changed in such a way that part of the village became an Electoral-Trier fief and another became subject to the Barons of Schmidtburg. Beginning in the Late Middle Ages, Laufersweiler belonged to the High Court of Rhaunen. In 1563, Laufersweiler had 34 or 35 households that were subject to various lords.

Ecclesiastical history.

The first documentary mention of any church building in Laufersweiler comes from 1405 and tells of a chapel consecrated to Mary. It is unknown, however, when Saint Lawrence's Church, which burnt down in 1839, was built. This church was subject first to the parish of Hausen. After the Reformation had been lastingly established in the 1560s by the Wild- and Rhinegraves, Laufersweiler became an autonomous Evangelical parish by 1602. The first rectory was built in 1617. Already by about 1645, towards the end of the Thirty Years' War, the Hunsrück was occupied for the first tome by the French, as it later was once again in King Louis XIV's wars of conquest. About 1685, on French demands, Saint Lawrence's Church ("Kirche St. Laurentius") was made a simultaneous church in which both Evangelical and Catholic services were to be held.

Coaching inn.

Beginning in the mid 16th century, there was in Laufersweiler a coaching inn ("Poststation") on the Dutch Postal Route ("Niederländischer Postkurs") from Brussels to Augsburg, Innsbruck, Trento, Venice, Milan and Rome. This postal way station was first mentioned in the documents about the 1561 mail robbery, when the horse-borne post was attacked on the way from Laufersweiler to Eckweiler (now a ghost village). According to these documents, in 1561, a man named Hans from Wittlich was the innkeeper. His successor in the late 16th century was Niclas Faust, who founded a “dynasty of innkeepers”. The inn lasted even through the 18th century. In 1867, Laufersweiler lay on a newly established postal route from Kirn to Büchenbeuren. In 1886, the inn was reorganized as a Deutsche Reichspost postal agency ("Postagentur"; run not by the postal service, but by a private agent). This lasted until 1994.

After the French Revolution.

After the French Revolution, the Rhine’s left bank, and thereby Laufersweiler too, were ceded to France in 1794. In 1815 Laufersweiler was assigned to the Kingdom of Prussia at the Congress of Vienna. After the great fire of 1839, which also destroyed the church, a new simultaneous church was built in 1842. Only in 1892 and 1893 did the Evangelicals finally have their own church, built in Romanesque Revival style.  By the 18th century, Laufersweiler had a Jewish community. The first synagogue was built before 1832. The one built in 1910 and 1911 was extensively vandalized by Nazi hooligans on Kristallnacht (9–10 November 1938). In the years that followed, 24 Jewish inhabitants fell victim to the Holocaust. In 1986, the synagogue was restored.  Since 1946, Laufersweiler has been part of the then newly founded state of Rhineland-Palatinate. Since administrative reform in 1970, Laufersweiler has belonged to the "Verbandsgemeinde" of Kirchberg.

Politics.

Municipal council.

The council is made up of 12 council members, who were elected by proportional representation at the municipal election held on 7 June 2009, and the honorary mayor as chairman.  The municipal election held on 7 June 2009 yielded the following results:

Mayor.

Laufersweiler's mayor is Günter Heck (FWG Laufersweiler e.V.), and his deputies are Rudi Schneider (WG Schneider) and Uschi Körner (SPD).

Coat of arms.

The German blazon reads:  The municipality's arms might in English heraldic language be described thus: Per fess argent a cross gules and sable an arming buckle of the first.  The Cross of Trier in the upper part of the escutcheon recalls Laufersweiler's former allegiance to the Electorate of Trier, which bore this device in its arms. Likewise, the charge below this, the buckle, refers to a former lord, the "Schenk" of Schmidtburg, whose arms bore this device.

Culture and sightseeing.

Buildings.

The following are listed buildings or sites in Rhineland-Palatinate’s Directory of Cultural Monuments:

More about buildings.

Housed in the former synagogue is a museum of Jewish history in the Hunsrück. A document collection, which forms part of the permanent exhibit, can be viewed here.  In the Lower Village ("Unterdorf") and on Kirchgasse are found timber-frame buildings with carved doors that are worth seeing.  The former town hall comes from the 17th century. Particularly worthy of mention here is the jetty on the upper floor with the former quarters for vagabonds.

Clubs.

Laufersweiler has several clubs:

Laufersweiler is an "Ortsgemeinde" – a municipality belonging to a "Verbandsgemeinde", a kind of collective municipality – in the Rhein-Hunsrück-Kreis (district) in Rhineland-Palatinate, Germany. It belongs to the "Verbandsgemeinde" of Kirchberg, whose seat is in the like-named town.

劳弗斯韦勒(德语:)是德国莱茵兰-普法尔茨州的一个小镇。总面积6.79平方公里,总人口842人,其中男性429人,女性413人(2011年12月31日),人口密度124人/平方公里。该镇有一系列观光景点及6家有名的俱乐部。同时也诞生了Aloys Felke、Günter Felke、Michael Felke几位名人。当前镇长是Günter Heck。


Signs and symptoms.

Most cases of HCC occur in people who already have signs and symptoms of chronic liver disease. They may present either with worsening of symptoms or may be without symptoms at the time of cancer detection. HCC may directly present with yellow skin, abdominal swelling due to fluid in the abdominal cavity, easy bruising from blood clotting abnormalities, loss of appetite, unintentional weight loss, abdominal pain, nausea, vomiting, or feeling tired.

Risk factors.

HCC mostly occurs in people with cirrhosis of the liver, and so risk factors generally include factors which cause chronic liver disease that may lead to cirrhosis. Still, certain risk factors are much more highly associated with HCC than others. For example, while heavy alcohol consumption is estimated to cause 60–70% of cirrhosis, the vast majority of HCC occurs in cirrhosis attributed to viral hepatitis (although there may be overlap). Recognized risk factors include:  The significance of these risk factors varies globally. In regions where hepatitis B infection is endemic, such as southeast China, this is the predominant cause. In populations largely protected by hepatitis B vaccination, such as the United States, HCC is most often linked to causes of cirrhosis such as chronic hepatitis C, obesity, and alcohol abuse.  Certain benign liver tumors, such as hepatocellular adenoma, may sometimes be associated with coexisting malignant HCC. Evidence is limited for the true incidence of malignancy associated with benign adenomas; however, the size of hepatic adenoma is considered to correspond to risk of malignancy and so larger tumors may be surgically removed. Certain subtypes of adenoma, particularly those with β-catenin activation mutation, are particularly associated with increased risk of HCC.  Children and adolescents are unlikely to have chronic liver disease, but if they suffer from congenital liver disorders, this fact increases the chance of developing HCC. Specifically, children with biliary atresia, infantile cholestasis, glycogen-storage diseases, and other cirrhotic diseases of the liver are predisposed to developing HCC in childhood.  Young adults afflicted by the rare fibrolamellar variant of hepatocellular carcinoma may have none of the typical risk factors, i.e. cirrhosis and hepatitis.

Diabetes mellitus.

The risk of hepatocellular carcinoma in type 2 diabetics is greater (from 2.5 to 7.1 times the nondiabetic risk) depending on the duration of diabetes and treatment protocol. A suspected contributor to this increased risk is circulating insulin concentration such that diabetics with poor insulin control or on treatments that elevate their insulin output (both states that contribute to a higher circulating insulin concentration) show far greater risk of hepatocellular carcinoma than diabetics on treatments that reduce circulating insulin concentration. On this note, some diabetics who engage in tight insulin control (by keeping it from being elevated) show risk levels low enough to be indistinguishable from the general population. This phenomenon is thus not isolated to diabetes mellitus type 2, since poor insulin regulation is also found in other conditions such as metabolic syndrome (specifically, when evidence of nonalcoholic fatty liver disease or NAFLD is present) and again evidence of greater risk exists here, too. While there are claims that anabolic steroid abusers are at greater risk (theorized to be due to insulin and IGF exacerbation), the only evidence that has been confirmed is that anabolic steroid users are more likely to have hepatocellular adenomas (a benign form of HCC) transform into the more dangerous hepatocellular carcinoma.

Pathogenesis.

Hepatocellular carcinoma, like any other cancer, develops when epigenetic alterations and mutations affecting the cellular machinery cause the cell to replicate at a higher rate and/or result in the cell avoiding apoptosis.  In particular, chronic infections of hepatitis B and/or C can aid the development of hepatocellular carcinoma by repeatedly causing the body's own immune system to attack the liver cells, some of which are infected by the virus, others merely bystanders. Activated immune-system inflammatory cells release free radicals, such as reactive oxygen species and nitric oxide reactive species, which in turn can cause DNA damage and lead to carcinogenic gene mutations. Reactive oxygen species also cause epigenetic alterations at the sites of DNA repair.  While this constant cycle of damage followed by repair can lead to mistakes during repair, which in turn lead to carcinogenesis, this hypothesis is more applicable, at present, to hepatitis C. Chronic hepatitis C causes HCC through the stage of cirrhosis. In chronic hepatitis B, however, the integration of the viral genome into infected cells can directly induce a noncirrhotic liver to develop HCC. Alternatively, repeated consumption of large amounts of ethanol can have a similar effect. The toxin aflatoxin from certain "Aspergillus" species of fungi is a carcinogen and aids carcinogenesis of hepatocellular cancer by building up in the liver. The combined high prevalence of rates of aflatoxin and hepatitis B in settings such as China and West Africa has led to relatively high rates of hepatocellular carcinoma in these regions. Other viral hepatitides such as hepatitis A have no potential to become a chronic infection, thus are not related to HCC.

Diagnosis.

Methods of diagnosis in HCC have evolved with the improvement in medical imaging. The evaluation of both asymptomatic patients and those with symptoms of liver disease involves blood testing and imaging evaluation. Although historically a biopsy of the tumor was required to prove the diagnosis, imaging (especially MRI) findings may be conclusive enough to obviate histopathologic confirmation.

Screening.

HCC remains associated with a high mortality rate, in part related to initial diagnosis commonly at an advanced stage of disease. As with other cancers, outcomes are significanty improved if treatment is initiated earlier in the disease process. Because the vast majority of HCC occurs in people with certain chronic liver diseases, especially those with cirrhosis, liver screening is commonly advocated in this population. Specific screening guidelines continue to evolve over time as evidence of its clinical impact becomes available. In the United States, the most commonly observed guidelines are those published by the American Association for the Study of Liver Diseases, which recommends screening people with cirrhosis with ultrasound every 6 months, with or without measurement of blood levels of tumor marker alpha-fetoprotein (AFP). Elevated levels of AFP are associated with active HCC disease, although inconsistently reliable. At levels >20 sensitivity is 41-65% and specificity is 80-94%. However, at levels >200 sensitivity is 31, specificity is 99%.  On ultrasound, HCC often appears as a small hypoechoic lesion with poorly defined margins and coarse, irregular internal echoes. When the tumor grows, it can sometimes appear heterogeneous with fibrosis, fatty change, and calcifications. This heterogeneity can look similar to cirrhosis and the surrounding liver parenchyma. A systematic review found that the sensitivity was 60% (95% CI 44–76%) and specificity was 97% (95% CI 95–98%) compared with pathologic examination of an explanted or resected liver as the reference standard. The sensitivity increases to 79% with AFP correlation.  Controversy remains as to the most effective screening protocols. For example, while some data support decreased mortality related to screening in people with hepatitis B infection, the AASLD notes. “there are no randomized trials [for screening] in Western populations with cirrhosis secondary to chronic hepatitis C or fatty liver disease, and thus there is some controversy surrounding whether surveillance truly leads to a reduction in mortality in this population of patients with cirrhosis.”

Higher risk people.

In a person where a higher suspicion of HCC exists, such as a person with symptoms or abnormal blood tests (i.e. alpha-fetoprotein and des-gamma carboxyprothrombin levels), evaluation requires imaging of the liver by CT or MRI scans. Optimally, these scans are performed with intravenous contrast in multiple phases of hepatic perfusion to improve detection and accurate classification of any liver lesions by the interpreting radiologist. Due to the characteristic blood flow pattern of HCC tumors, a specific perfusion pattern of any detected liver lesion may conclusively detect an HCC tumor. Alternatively, the scan may detect an indeterminate lesion and further evaluation may be performed by obtaining a physical sample of the lesion.

Imaging.

Ultrasound, CT scan, and MRI may be used to evaluate the liver for HCC. On CT and MRI, HCC can have three distinct patterns of growth:  A systematic review of CT diagnosis found that the sensitivity was 68% (95% CI 55–80%) and specificity was 93% (95% CI 89–96%) compared with pathologic examination of an explanted or resected liver as the reference standard. With triple-phase helical CT, the sensitivity was 90% or higher, but these data have not been confirmed with autopsy studies.  However, MRI has the advantage of delivering high-resolution images of the liver without ionizing radiation. HCC appears as a high-intensity pattern on T2-weighted images and a low-intensity pattern on T1-weighted images. The advantage of MRI is that it has improved sensitivity and specificity when compared to ultrasound and CT in cirrhotic patients with whom it can be difficult to differentiate HCC from regenerative nodules. A systematic review found that the sensitivity was 81% (95% CI 70–91%) and specificity was 85% (95% CI 77–93%) compared with pathologic examination of an explanted or resected liver as the reference standard. The sensitivity is further increased if gadolinium contrast-enhanced and diffusion-weighted imaging are combined.  MRI is more sensitive and specific than CT.  Liver image reporting and data system (LI-RADS) is a classification system for the reporting of liver lesions detected on CT and MRI. Radiologists use this standardized system to report on suspicious lesions and to provide an estimated likelihood of malignancy. Categories range from LI-RADS (LR) 1 to 5, in order of concern for cancer. A biopsy is not needed to confirm the diagnosis of HCC if certain imaging criteria are met.

Pathology.

Macroscopically, liver cancer appears as a nodular or infiltrative tumor. The nodular type may be solitary (large mass) or multiple (when developed as a complication of cirrhosis). Tumor nodules are round to oval, gray or green (if the tumor produces bile), well circumscribed but not encapsulated. The diffuse type is poorly circumscribed and infiltrates the portal veins, or the hepatic veins (rarely).  Microscopically, the four architectural and cytological types (patterns) of hepatocellular carcinoma are: fibrolamellar, pseudoglandular (adenoid), pleomorphic (giant cell), and clear cell. In well-differentiated forms, tumor cells resemble hepatocytes, form trabeculae, cords, and nests, and may contain bile pigment in the cytoplasm. In poorly differentiated forms, malignant epithelial cells are discohesive, pleomorphic, anaplastic, and giant. The tumor has a scant stroma and central necrosis because of the poor vascularization. A fifth form – lymphoepithelioma like hepatocellular carcinoma – has also been described.

Staging.

BCLC Staging System  The prognosis of HCC is affected by the staging of the tumor and the liver's function due to the effects of liver cirrhosis.  A number of staging classifications for HCC are available; however, due to the unique nature of the carcinoma to fully encompass all the features that affect the categorization of the HCC, a classification system should incorporate tumor size and number, presence of vascular invasion and extrahepatic spread, liver function (levels of serum bilirubin and albumin, presence of ascites, and portal hypertension) and general health status of the patient (defined by the ECOG classification and the presence of symptoms).  Of all the staging classification systems available the Barcelona Clinic Liver Cancer staging classification encompasses all of the above characteristics. This staging classification can be used to select people for treatment.  Important features that guide treatment include:  MRI is the best imaging method to detect the presence of a tumor capsule.  The most common sites of metastasis are the lung, abdominal lymph nodes, and bone.

Prevention.

Since hepatitis B and C are some of the main causes of hepatocellular carcinoma, prevention of infection is key to then prevent HCC. Thus, childhood vaccination against hepatitis B may reduce the risk of liver cancer in the future. In the case of patients with cirrhosis, alcohol consumption is to be avoided. Also, screening for hemochromatosis may be beneficial for some patients. Whether screening those with chronic liver disease for HCC improves outcomes is unclear.

Treatment.

Treatment of hepatocellular carcinoma varies by the stage of disease, a person's likelihood to tolerate surgery, and availability of liver transplant:  Loco-regional therapy (also referred to as liver-directed therapy) refers to any one of several minimally-invasive treatment techniques to focally target HCC within the liver. These procedures are alternatives to surgery, and may be considered in combination with other strategies, such as a later liver transplantation. Generally, these treatment procedures are performed by interventional radiologists or surgeons, in coordination with a medical oncologist. Loco-regional therapy may refer to either percutaneous therapies (e.g. cryoablation), or arterial catheter-based therapies (chemoembolization or radioembolization).

Surgical resection.

Surgical removal of the tumor is associated with better cancer prognosis, but only 5–15% of patients are suitable for surgical resection due to the extent of disease or poor liver function. Surgery is only considered if the entire tumor can be safely removed while preserving sufficient functional liver to maintain normal physiology. Thus, preoperative imaging assessment is critical to determine both the extent of HCC and to estimate the amount of residual liver remaining after surgery. To maintain liver function, residual liver volume should exceed 25% of total liver volume in a noncirrhotic liver, greater than 40% in a cirrhotic liver. Surgery on diseased or cirrhotic livers is generally associated with higher morbidity and mortality. The overall recurrence rate after resection is 50-60%. The Singapore Liver Cancer Recurrence score can be used to estimate risk of recurrence after surgery.

Liver transplantation.

Liver transplantation, replacing the diseased liver with a cadaveric or a living donor liver, plays an increasing role in treatment of HCC. Although outcomes following liver transplant were initially poor (20%–36% survival rate), outcomes have significantly improved with improvement in surgical techniques and adoption of the Milan criteria at US transplantation centers. Expanded Shanghai criteria in China have resulted in overall survival and disease-free survival rates similar to those achieved using the Milan criteria. Studies from the late 2000s obtained higher survival rates ranging from 67% to 91%.  The risks of liver transplantation extend beyond risk of the procedure itself. The immunosuppressive medication required after surgery to prevent rejection of the donor liver also impairs the body's natural ability to combat dysfunctional cells. If the tumor has spread undetected outside the liver before the transplant, the medication effectively increases the rate of disease progression and decreases survival. With this in mind, liver transplant "can be a curative approach for patients with advanced HCC without extrahepatic metastasis". In fact, among patients with compensated cirrhosis, transplantation is not associated with improved survival compared to hepatectomy, but instead is significantly more expensive. Patient selection is considered a major key for success.

Systemic.

In disease which has spread beyond the liver, systemic therapy may be a consideration. In 2007, Sorafenib, an oral multikinase inhibitor, was the first systemic agent approved for first-line treatment of advanced HCC. Trials have found modest improvement in overall survival: 10.7 months vs 7.9 months and 6.5 months vs 4.2 months.  The most common side effects of Sorafenib include a hand-foot skin reaction and diarrhea. Sorafenib is thought to work by blocking growth of both tumor cells and new blood vessels. Numerous other molecular targeted drugs are being tested as alternative first- and second-line treatments for advanced HCC.

Prognosis.

The usual outcome is poor, because only 10–20% of hepatocellular carcinomas can be removed completely using surgery. If the cancer cannot be completely removed, the disease is usually deadly within 3 to 6 months. This is partially due to late presentation with tumors, but also the lack of medical expertise and facilities in the regions with high HCC prevalence. However, survival can vary, and occasionally people survive much longer than 6 months. The prognosis for metastatic or unresectable HCC has improved due to the approval of Sorafenib (Nexavar®) for advanced HCC.

Epidemiology.

HCC is one of the most common tumors worldwide. The epidemiology of HCC exhibits two main patterns, one in North America and Western Europe and another in non-Western countries, such as those in sub-Saharan Africa, Central and Southeast Asia, and the Amazon basin. Males are affected more than females usually, and it is most common between the ages of 30 and 50, Hepatocellular carcinoma causes 662,000 deaths worldwide per year about half of them in China.

Africa and Asia.

In some parts of the world, such as sub-Saharan Africa and Southeast Asia, HCC is the most common cancer, generally affecting men more than women, and with an age of onset between the late teens and 30s. This variability is in part due to the different patterns of hepatitis B and hepatitis C transmission in different populations – infection at or around birth predispose to earlier cancers than if people are infected later. The time between hepatitis B infection and development into HCC can be years, even decades, but from diagnosis of HCC to death, the average survival period is only 5.9 months according to one Chinese study during the 1970-80s, or 3 months (median survival time) in sub-Saharan Africa according to Manson's textbook of tropical diseases. HCC is one of the deadliest cancers in China, where chronic hepatitis B is found in 90% of cases. In Japan, chronic hepatitis C is associated with 90% of HCC cases. Foods infected with "Aspergillus flavus" (especially peanuts and corns stored during prolonged wet seasons) which produces aflatoxins pose another risk factor for HCC.

North America and Western Europe.

The most common malignant tumors in the liver represent metastases (spread) from tumors which originate elsewhere in the body. Among cancers that originate from liver tissue, HCC is the most common primary liver cancer. In the United States, the US surveillance, epidemiology, and end results database program, shows that HCC accounts for 65% of all cases of liver cancers. As screening programs are in place for high-risk persons with chronic liver disease, HCC is often discovered much earlier in Western countries than in developing regions such as sub-Saharan Africa.  Acute and chronic hepatic porphyrias (acute intermittent porphyria, porphyria cutanea tarda, hereditary coproporphyria, variegate porphyria) and tyrosinemia type I are risk factors for hepatocellular carcinoma. The diagnosis of an acute hepatic porphyria (AIP, HCP, VP) should be sought in patients with HCC without typical risk factors of hepatitis B or C, alcoholic liver cirrhosis, or hemochromatosis. Both active and latent genetic carriers of acute hepatic porphyrias are at risk for this cancer, although latent genetic carriers have developed the cancer at a later age than those with classic symptoms. Patients with acute hepatic porphyrias should be monitored for HCC.  The incidence of HCC is relatively lower in the Western Hemisphere than in Eastern Asia. However, despite the statistics being low, the diagnosis of HCC has increased since the 1980s and it is continuing to increase, making it one of the rising causes of death due to cancer. The common risk factor for HCC is hepatitis C, along with other health issues.

Research.

Preclinical.

Mipsagargin (G-202), has orphan drug designation as a treatment during chemotherapy for HCC. It is a thapsigargin-based prodrug with cytotoxic activity used to reduce blood flow to the tumor during treatment. Results from Phase 2 trial recommended G-202 as a first-in-class PSMA-targeted prodrug and that it move to clinical trials.  Current research includes the search for the genes that are disregulated in HCC, antiheparanase antibodies, protein markers, non-coding RNAs (such as TUC338) and other predictive biomarkers. As similar research is yielding results in various other malignant diseases, it is hoped that identifying the aberrant genes and the resultant proteins could lead to the identification of pharmacological interventions for HCC.  The development of three-dimensional culture methods provides a new approach for preclinical studies of cancer therapy using patient-derived organoids. These miniaturized organoid 'avatars' of a patient's tumor recapitulate several features of the original tumor, rendering them an attractive model for drug-sensitivity testing and precision medicine for HCC and other types of primary liver cancer.  Furthermore, HCC occurs in patients with liver disease. A biomarker named six-miRNA signature allows effective treatment of patients with HCC and is able to predict its recurrence in the liver.

Clinical.

JX-594, an oncolytic virus, has orphan drug designation for this condition and is undergoing clinical trials. Hepcortespenlisimut-L (Hepko-V5), an oral cancer vaccine, also has US FDA orphan drug designation for HCC. Immunitor Inc. completed a Phase II trial, published in 2017.  A randomized trial of people with advanced HCC showed no benefit for the combination of everolimus and pasireotide.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults, and is the most common cause of death in people with cirrhosis. It occurs in the setting of chronic liver inflammation, and is most closely linked to chronic viral hepatitis infection (hepatitis B or C) or exposure to toxins such as alcohol or aflatoxin. Certain diseases, such as hemochromatosis and alpha 1-antitrypsin deficiency, markedly increase the risk of developing HCC. Metabolic syndrome and NASH are also increasingly recognized as risk factors for HCC. As with any cancer, the treatment and prognosis of HCC vary depending on the specifics of tumor histology, size, how far the cancer has spread, and overall health. The vast majority of HCC occurs in Asia and sub-Saharan Africa, in countries where hepatitis B infection is endemic and many are infected from birth. The incidence of HCC in the United States and other developing countries is increasing due to an increase in hepatitis C virus infections. It is more common in males than females for unknown reasons.

肝细胞癌 (Hepatocellular carcinoma,简称HCC)是成年人中最常见类型的慢性肝癌,并且在肝硬化的患者中也是最常见的死亡原因。


History.

Coffee House.

The Royal Exchange had been founded by English financier Thomas Gresham and Sir Richard Clough on the model of the Antwerp Bourse. It was opened by Elizabeth I of England in 1571.  During the 17th century, stockbrokers were not allowed in the Royal Exchange due to their rude manners. They had to operate from other establishments in the vicinity, notably Jonathan's Coffee-House. At that coffee house, a broker named John Castaing started listing the prices of a few commodities, such as salt, coal, and paper, and exchange rates in 1698. Originally, this was not a daily list and was only published a few days of the week.  This list and activity was later moved to Garraway's coffee house. Public auctions during this period were conducted for the duration that a length of tallow candle could burn; these were known as "by inch of candle" auctions. As stocks grew, with new companies joining to raise capital, the royal court also raised some monies. These are the earliest evidence of organised trading in marketable securities in London.

Royal Exchange.

After Gresham's Royal Exchange building was destroyed in the Great Fire of London, it was rebuilt and re-established in 1669. This was a move away from coffee houses and a step towards the modern model of stock exchange.  The Royal Exchange housed not only brokers but also merchants and merchandise. This was the birth of a regulated stock market, which had teething problems in the shape of unlicensed brokers. In order to regulate these, Parliament passed an Act in 1697 that levied heavy penalties, both financial and physical, on those brokering without a licence. It also set a fixed number of brokers (at 100), but this was later increased as the size of the trade grew. This limit led to several problems, one of which was that traders began leaving the Royal Exchange, either by their own decision or through expulsion, and started dealing in the streets of London. The street in which they were now dealing was known as 'Exchange Alley', or 'Change Alley'; it was suitably placed close to the Bank of England. Parliament tried to regulate this and ban the unofficial traders from the Change streets.  Traders became weary of "bubbles" when companies rose quickly and fell, so they persuaded Parliament to pass a clause preventing "unchartered" companies from forming.  After the Seven Years' War (1756–1763), trade at Jonathan's Coffee House boomed again. In 1773, Jonathan, together with 150 other brokers, formed a club and opened a new and more formal "Stock Exchange" in Sweeting's Alley. This now had a set entrance fee, by which traders could enter the stock room and trade securities. It was, however, not an exclusive location for trading, as trading also occurred in the Rotunda of the Bank of England. Fraud was also rife during these times and in order to deter such dealings, it was suggested that users of the stock room pay an increased fee. This was not met well and ultimately, the solution came in the form of annual fees and turning the Exchange into a Subscription room.  The Subscription room created in 1801 was the first regulated exchange in London, but the transformation was not welcomed by all parties. On the first day of trading, non-members had to be expelled by a constable. In spite of the disorder, a new and bigger building was planned, at Capel Court.  William Hammond laid the first foundation stone for the new building on 18 May. It was finished on 30 December when "The Stock Exchange" was incised on the entrance.

First Rule Book.

In the Exchange's first operating years, on several occasions there was no clear set of regulations or fundamental laws for the Capel Court trading. In February 1812, the General Purpose Committee confirmed a set of recommendations, which later became the foundation of the first codified rule book of the Exchange. Even though the document was not a complex one, topics such as settlement and default were, in fact, quite comprehensive.  With its new governmental commandments and increasing trading volume, the Exchange was progressively becoming an accepted part of the financial life in the City. In spite of continuous criticism from newspapers and the public, the government used the Exchange's organised market (and would most likely not have managed without it) to raise the enormous amount of money required for the wars against Napoleon.

Foreign and regional exchanges.

After the war and facing a booming world economy, foreign lending to countries such as Brazil, Peru and Chile was a growing market. Notably, the Foreign Market at the Exchange allowed for merchants and traders to participate, and the Royal Exchange hosted all transactions where foreign parties were involved. The constant increase in overseas business eventually meant that dealing in foreign securities had to be allowed within all of the Exchange's premises.  Just as London enjoyed growth through international trade, the rest of Great Britain also benefited from the economic boom. Two other cities, in particular, showed great business development: Liverpool and Manchester. Consequently, in 1836 both the Manchester and Liverpool stock exchanges were opened. Some stock prices sometimes rose by 10%, 20% or even 30% in a week. These were times when stockbroking was considered a real business profession, and such attracted many entrepreneurs. Nevertheless, with booms came busts, and in 1835 the "Spanish panic" hit the markets, followed by a second one two years later.

The Exchange before the World Wars.

By June 1853, both participating members and brokers were taking up so much space that the Exchange was now uncomfortably crowded, and continual expansion plans were taking place. Having already been extended west, east and northwards, it was then decided the Exchange needed an entire new establishment. Thomas Allason was appointed as the main architect, and in March 1854 the new brick building inspired from the Great Exhibition stood ready. This was a huge improvement in both surroundings and space, with twice the floor space available.  By the late 1800s, the telephone, ticker tape and the telegraph had been invented. Those new technologies led to a revolution in the work of the Exchange.

First World War.

As the financial centre of the world, both the City and the Stock Exchange were hit hard by the outbreak of World War I in 1914. Due to fears that borrowed money was to be called in and that foreign banks would demand their loans or raise interest, prices surged at first. The decision to close the Exchange for improved breathing space and to extend the August Bank Holiday to prohibit a run on banks, was hurried through by the committee and Parliament, respectively. The Stock Exchange ended up being closed from the end of July until the New Year, causing street business to be introduced again as well as the "challenge system".  The Exchange was set to open again on 4 January 1915 under tedious restrictions: transactions were to be in cash only. Due to the limitations and challenges on trading brought by the war, almost a thousand members quit the Exchange between 1914 and 1918. When peace returned in November 1918, the mood on the trading floor was generally cowed. In 1923 the Exchange received its own coat of arms, with the motto "Dictum Meum Pactum", My Word is My Bond.

Second World War.

In 1937 officials at the Exchange used their experiences from World War I to draw up plans for how to handle a new war. The main concerns included air raids and the subsequent bombing of the Exchange's perimeters, and one suggestion was a move to Denham, Buckinghamshire. This however never took place. On the first day of September 1939, the Exchange closed its doors "until further notice" and two days later World War II was declared. Unlike in the prior war, the Exchange opened its doors again six days later, on 7 September.  As the war escalated into its second year, the concerns for air raids were greater than ever. Eventually, on the night of 29 December 1940 one of the greatest fires in London's history took place. The Exchange's floor was hit by a clutch of incendiary bombs, which were extinguished quickly. Trading on the floor was now drastically low and most was done over the phone to reduce the possibility of injuries.  The Exchange was only closed for one more day during wartime, in 1945 due to damage from a V-2 rocket. Nonetheless trading continued in the house's basement.

Post-war.

After decades of uncertain if not turbulent times, stock market business boomed in the late 1950s. This spurred officials to find new, more suitable accommodation. The work on the new Stock Exchange Tower began in 1967. The Exchange's new 321 feet (96 metre) high building had 26 storeys with council and administration at the top, and middle floors let out to affiliate companies. Queen Elizabeth II opened the building on 8 November 1972; it was a new City landmark, with its trading floor. 1973 marked a year of changes for the Stock Exchange. First, two trading prohibitions were abolished. A report from the Monopolies and Mergers Commission recommended the admittance of both women and foreign-born members on the floor. Second, in March the London Stock Exchange formally merged with the eleven British and Irish regional exchanges, including the Scottish Stock Exchange. This expansion led to the creation of a new position of Chief Executive Officer; after an extensive search this post was given to Robert Fell. There were more governance changes in 1991, when the governing Council of the Exchange was replaced by a Board of Directors drawn from the Exchange's executive, customer and user base; and the trading name became "The London Stock Exchange".  FTSE 100 Index (pronounced "Footsie 100") was launched by a partership of the "Financial Times" and the Stock Exchange on 3 January 1984. This turned out to be one of the most useful indices of all, and tracked the movements of the 100 leading companies listed on the Exchange.

IRA bombing.

On 20 July 1990 a bomb planted by the Provisional Irish Republican Army exploded in the men's toilets behind the visitors' gallery. The area had already been evacuated and nobody was injured. About 30 minutes before the blast at 8:49 a.m., a man who said he was a member of the IRA told Reuters that a bomb had been placed at the exchange and was about to explode. Police officials said that if there had been no warning, the human toll would have been very high. The explosion ripped a hole in the 23-storey building in Threadneedle Street and sent a shower of glass and concrete onto the street. The long-term trend towards electronic trading platforms reduced the Exchange's attraction to visitors, and although the gallery reopened, it was closed permanently in 1992.

"Big Bang".

The biggest event of the 1980s was the sudden de-regulation of the financial markets in the UK in 1986. The phrase "Big Bang" was coined to describe measures, including abolition of fixed commission charges and of the distinction between stockjobbers and stockbrokers on the London Stock Exchange, as well as the change from an open outcry to electronic, screen-based trading.  In 1995, the Exchange launched the Alternative Investment Market, the AIM, to allow growing companies to expand into international markets. Two years later the Electronic Trading Service (SETS) was launched, bringing greater speed and efficiency to the market. Next, the CREST settlement service was launched. In 2000, the Exchange's shareholders voted to become a public limited company, London Stock Exchange plc. London Stock Exchange also transferred its role as UK Listing Authority to the Financial Services Authority (FSA-UKLA).  EDX London, an international equity derivatives business, was created in 2003 in partnership with OM Group. The Exchange also acquired Proquote Limited, a new generation supplier of real-time market data and trading systems.  The old Stock Exchange Tower became largely redundant with Big Bang, which deregulated many of the Stock Exchange's activities: computerised systems and dealing rooms replaced face-to-face trading. In 2004 LondonStock Exchange moved to a brand-new headquarters in Paternoster Square, close to St Paul's Cathedral.  In 2007, the London Stock Exchange merged with Borsa Italiana, creating London Stock Exchange Group (LSEG). The Group's headquarters are in Paternoster Square.

Occupy London.

The Stock Exchange in Paternoster Square was the initial target for the protesters of Occupy London on 15 October 2011. Attempts to occupy the square were thwarted by police. Police sealed off the entrance to the square as it is private property, a High Court injunction having previously been granted against public access to the square.  The protesters moved nearby to occupy the space in front of St Paul's Cathedral. The protests were part of the global Occupy movement.

Extinction Rebellion.

On 25 April 2019, the final day of the Extinction Rebellion disruption in London, 13 activists glued themselves together in a chain, blocking the entrances of the Stock Exchange. The protesters were all later arrested on suspicion of aggravated trespass.  Extinction Rebellion had said its protesters would target the financial industry "and the corrosive impacts of the... sector on the world we live in" and activists also blocked entrances to HM Treasury and the Goldman Sachs office on Fleet Street.

Activities.

Primary markets.

Issuer services help companies from around the world to join the London equity market in order to gain access to capital. London Stock Exchange allows companies to raise money, increase their profile and obtain a market valuation through a variety of routes, thus following the firms throughout the whole IPO process.  London Stock Exchange runs several markets for listing, giving an opportunity for different sized companies to list. International companies can list a number of products in London including shares, depositary receipts and debt, offering different and cost-effective ways to raise capital. In 2004 the Exchange opened a Hong Kong office and has attracted more than 200 companies from the Asia-Pacific region.  For the biggest companies exists the Premium Listed Main Market. This operates a Super Equivalence method where conditions of both the UK Listing Authority as well as London Stock Exchange's own criteria have to be met. The largest IPO on the Exchange was completed in May 2011 by Glencore International plc. The company raised $10 billion at admission, making it one of the largest IPOs ever since foundation.  In terms of smaller SME's London Stock Exchange operates the Alternative Investment Market (AIM). For international companies that fall outside of the EU, it operates the Depository Receipt (DR) scheme as a way of listing and raising capital.  There are also two specialised markets:  Professional Securities Market This market facilitates the raising of capital through the issue of specialist debt securities or depositary receipts (DRs) to professional investors. The market operates under the status as a Recognised Investment Exchange, and by July 2011 it had 32 DRs, 108 Eurobonds and over 350 Medium Term Notes.  Specialist Fund Market Is London Stock Exchange's dedicated market, designed to accept more sophisticated fund vehicles, governance models and security. It is suitable only for institutional, professional and highly knowledgeable investors. The Specialist Fund Market is an EU Regulated Market and thus securities admitted to the market are eligible for most investor mandates providing a pool of liquidity for issuers admitted to the market

Secondary markets.

The securities available for trading on London Stock Exchange:  There are two main markets on which companies trade on the LSE:

Main Market.

The main market is home to over 1,300 large companies from 60 different countries. Over the past 10 years over £366 billion has been raised through new and further issues by Main Market companies. The FTSE 100 Index ("footsie") is the main share index of the 100 most highly capitalised UK companies listed on the Main Market.

Alternative Investment Market.

The Alternative Investment Market is LSE's international market for smaller companies. A wide range of businesses including early-stage, venture capital-backed as well as more-established companies join AIM seeking access to growth capital. The AIM is classified as a Multilateral Trading Facility (MTF) under the 2004 MiFID directive, and as such it is a flexible market with a simpler admission process for companies wanting to be publicly listed.

Electronic platforms.

There are also several electronic platforms on which the different products trade: Trading of derivative products is available on the "Turquoise" platform (ex EDX London). Products are Norwegian Futures and options on Norwegian single stocks and indices, Russian futures and options on the most liquid IOB Depositary Receipts, Futures, options on the FTSE RIOB index and futures on the FTSE 100. Futures and options on the most liquid European stock underlyings and on European benchmark indices were expected to be launched in Q4 2011 and Q1 2012 subject to Financial Services Authority approval.

Fixed Income.

The largest products offered are:  The "Order book for Retail Bonds" (ORB), launched in February 2010, offers continuous two-way pricing for trading in UK gilts and retail-size corporate bonds on-exchange. ORB acts as an electronic secondary market for retail investors. 2009 saw highest-ever inflow into bond funds, a net total of £10.7bn, driven almost entirely by retail investors (90% of total), with corporate bonds being the bestselling sector.  ORB offers an open and transparent market model for trading in retail-size. Currently there are five dedicated market makers committed to quoting two-way prices in a range of retail bonds throughout the trading day. New market models means private investors will be able to see prices on-screen and trade in bonds in a similar way as they currently do for shares. This creates a greater efficiency of electronic on-book execution and option to use straight-through-processing to settlement system.  Retail Bonds are driven by cost-effectiveness, simplicity of transaction charging and standardisation of market structure. The key aim of ORB is to increase distribution for bonds by opening up these markets to private investors who may have previously felt excluded from this market. This is by increasing the availability of publication on offer, detailing the risks and benefits involved in Retail Bonds, such as taxation.  New entrants into ORB have been able to raise sufficient funds, such as Places for People who were able to raise capital of £140 million. This portrays the advantage using ORB can have, even for non-bank smaller firms seeking to raise capital.

Statistics.

There are currently 2,600 companies from over 60 countries listed on London Stock Exchange, of which 1151 are on AIM, 44 on the Professional Securities Market and 10 on the Specialist Funds Market. Pence sterling (GBX) is a subdivision of Pounds sterling (GBP). Pounds sterling are the UK's major currency unit, but pence are often used when quoting prices; e.g. a quoted price of GBX 2,360 is equivalent to £23.60. , the AIM had 56 companies as per country of operations from Africa, 41 from China, 26 from Latin America, 23 from Central & Eastern Europe and 29 from India & Bangladesh, making it one of the world's leading growth markets. Since its launch in 1995, more than £67 billion has been raised on AIM. The total market value of these companies was £3.9 trillion. The daily turnover in July 2011 was £4.4 billion (€5.0 billion) and the daily number of trades 611,941. The LSE's share of trading in the UK lit order book trading was 62.2%. London Stock Exchange offered trading in more emerging market exchange traded funds (ETFs) than any other exchange in the world. There were a total of 158 emerging market ETFs listed on the Exchange in May 2011, compared with 126 on the New York Stock Exchange (NYSE Arca) and 93 on Deutsche Börse.

Information services.

London Stock Exchange supplies its participants with real time prices and trading data creating the transparency and liquidity through several services. Feeds are also available through providers such as Bloomberg and Thomson Reuters. Some of the products and references provided by London Stock Exchange Group are:

Post trade.

LCH & CC&G  Through the Exchange's Italian arm, Borsa Italiana, the London Stock Exchange Group as a whole offers clearing and settlement services for trades through "CC&G" (Cassa di Compensazione e Garanzia) and Monte Titoli. is the Groups Central Counterparty (CCP) and covers multiple asset classes throughout the Italian equity, derivatives and bond markets. CC&G also clears Turquoise derivatives. "Monte Titoli" (MT) is the pre-settlement, settlement, custody and asset services provider of the Group. MT operates both on-exchange and OTC trades with over 400 banks and brokers.

Technology.

London Stock Exchange's trading platform is its own Linux-based edition named Millennium Exchange.  Their previous trading platform TradElect was based on Microsoft's.NET Framework, and was developed by Microsoft and Accenture. Microsoft used the LSE software as an example of the supposed superiority of Windows over Linux in the "Get the Facts" campaign, claiming that the LSE system provided "five nines" reliability, and a processing speed of 3–4 milliseconds. For Microsoft, LSE was a good combination of a highly visible exchange and yet a relatively modest IT problem.  Despite TradElect only being in use for about two years, after suffering multiple periods of extended downtime and unreliability the LSE announced in 2009 that it was planning to switch to Linux in 2010. The main market migration to MillenniumIT technology was successfully completed in February 2011.  LSEG provides high-performance technology, including trading, market surveillance and post-trade systems, for over 40 organisations and exchanges, including the Group's own markets. Additional services include network connectivity, hosting and quality assurance testing. MillenniumIT, GATElab and Exactpro are among the Group's technology companies.  The LSE facilitates stock listings in a currency other than its "home currency". Most stocks are quoted in GBP but some are quoted in EUR while others are quoted in USD.

Mergers and acquisitions.

Deutsche Börse.

On 3 May 2000, it was announced that the LSE would merge with the Deutsche Börse; however this fell through.

Borsa Italiana.

On 23 June 2007, the London Stock Exchange announced that it had agreed on the terms of a recommended offer to the shareholders of the Borsa Italiana S.p.A. The merger of the two companies created a leading diversified exchange group in Europe. The combined group was named the London Stock Exchange Group, but still remained two separate legal and regulatory entities. One of the long-term strategies of the joint company is to expand Borsa Italiana's efficient clearing services to other European markets.

MTS.

In 2007, after Borsa Italiana announced that it was exercising its call option to acquire full control of MBE Holdings; thus the combined Group would now control Mercato dei Titoli di Stato, or MTS. This merger of Borsa Italiana and MTS with LSE's existing bond-listing business enhanced the range of covered European fixed income markets.

Turquoise.

London Stock Exchange Group acquired Turquoise (TQ), a Pan-European MTF, in 2009 and since coupling with MillenniumIT's software, it currently offers the fastest latency of any in Europe. Currently the speed of latency on Turquoise (as measured at the end of August 2011) is 97 microseconds on average for 99.9% of trades. Initially founded by a consortium of nine banks, it is now majority-owned by the London Stock Exchange Group. Currently shareholders include twelve of the leading investment banks.  Turquoise operates a maker-taker fee scheme: 0.30 basis points for aggressive traders and 0.20 rebates for passive traders, providing liquidity. The market share of Turquoise as an MTF has doubled over the past twelve months, from 3% to 6%. There are currently 2,000 securities, across 19 countries that are on Turquoise. Unlike Broker-Dealer Crossing Networks, TQ does not discriminate as to who can trade on their platform.

NASDAQ bids.

In December 2005, London Stock Exchange rejected a £1.6 billion takeover offer from Macquarie Bank. London Stock Exchange described the offer as "derisory", a sentiment echoed by shareholders in the Exchange. Shortly after Macquarie withdrew its offer, the LSE received an unsolicited approach from NASDAQ valuing the company at £2.4 billion. This too it rejected. NASDAQ later pulled its bid, and less than two weeks later on 11 April 2006, struck a deal with LSE's largest shareholder, Ameriprise Financial's Threadneedle Asset Management unit, to acquire all of that firm's stake, consisting of 35.4 million shares, at £11.75 per share. NASDAQ also purchased 2.69 million additional shares, resulting in a total stake of 15%. While the seller of those shares was undisclosed, it occurred simultaneously with a sale by Scottish Widows of 2.69 million shares. The move was seen as an effort to force LSE to the negotiating table, as well as to limit the Exchange's strategic flexibility.  Subsequent purchases increased NASDAQ's stake to 25.1%, holding off competing bids for several months. United Kingdom financial rules required that NASDAQ wait for a period of time before renewing its effort. On 20 November 2006, within a month or two of the expiration of this period, NASDAQ increased its stake to 28.75% and launched a hostile offer at the minimum permitted bid of £12.43 per share, which was the highest NASDAQ had paid on the open market for its existing shares. The LSE immediately rejected this bid, stating that it "substantially undervalues" the company.  NASDAQ revised its offer (characterized as an "unsolicited" bid, rather than a "hostile takeover attempt") on 12 December 2006, indicating that it would be able to complete the deal with 50% (plus one share) of LSE's stock, rather than the 90% it had been seeking. The U.S. exchange did not, however, raise its bid. Many hedge funds had accumulated large positions within the LSE, and many managers of those funds, as well as Furse, indicated that the bid was still not satisfactory. NASDAQ's bid was made more difficult because it had described its offer as "final", which, under British bidding rules, restricted their ability to raise its offer except under certain circumstances.  In the end, NASDAQ's offer was roundly rejected by LSE shareholders. Having received acceptances of only 0.41% of rest of the register by the deadline on 10 February 2007, Nasdaq's offer duly lapsed. Responding to the news, Chris Gibson-Smith, the LSE's chairman, said: "The Exchange’s strategy has produced outstanding results for shareholders by facilitating a structural shift in volume growth in an increasingly international market at the centre of the world’s equity flows. The Exchange intends to build on its exceptionally valuable brand by progressing various competitive, collaborative and strategic opportunities, thereby reinforcing its uniquely powerful position in a fast evolving global sector."  On 20 August 2007, NASDAQ announced that it was abandoning its plan to take over the LSE and subsequently look for options to divest its 31% (61.3 million shares) shareholding in the company in light of its failed takeover attempt. In September 2007, NASDAQ agreed to sell the majority of its shares to Borse Dubai, leaving the United Arab Emirates-based exchange with 28% of the LSE.

Proposed merger with TMX Group.

On 9 February 2011, London Stock Exchange Group announced it had agreed to merge with the Toronto-based TMX Group, the owners of the Toronto Stock Exchange, creating a combined entity with a market capitalization of listed companies equal to £3.7 trillion. Xavier Rolet, CEO of the LSE Group at the time, would have headed the new enlarged company, while TMX Chief Executive Thomas Kloet would have become the new firm president. London Stock Exchange Group however announced it was terminating the merger with TMX on 29 June 2011 citing that "LSEG and TMX Group believe that the merger is highly unlikely to achieve the required two-thirds majority approval at the TMX Group shareholder meeting". Even though LSEG obtained the necessary support from its shareholders, it failed to obtain the required support from TMX's shareholders.

Opening times.

Normal trading sessions on the main orderbook (SETS) are from 08:00 to 16:30 local time every day of the week except Saturdays, Sundays and holidays declared by the exchange in advance. The detailed schedule is as follows:  Auction Periods (SETQx)  SETSqx (Stock Exchange Electronic Trading Service – quotes and crosses) is a trading service for securities less liquid than those traded on SETS.  The auction uncrossings are scheduled to take place at 8am, 9am, 11am, 2pm and 4:35pm.  Holidays are currently: New Year's Day, Good Friday, Easter Monday, May Bank Holiday, Spring Bank Holiday, Summer Bank Holiday, Christmas Day, and Boxing Day. If New Year's Day, Christmas Day, and/or Boxing Day is on a weekend, the following working day is a holiday.

London Stock Exchange is a stock exchange in the City of London, England., London Stock Exchange had a market capitalisation of US$4.59 trillion. It was founded in 1571, making it one of the oldest exchanges in the world. Its current premises are situated in Paternoster Square close to St Paul's Cathedral in the City of London. It is part of London Stock Exchange Group (LSEG). London Stock Exchange Group was created in October 2007 when London Stock Exchange merged with Milan Stock Exchange, Borsa Italiana.

伦敦证券交易所(简称伦敦证交所;英语:London Stock Exchange,缩写:LSE)是一家总部位于英国伦敦市的证券交易所,是欧洲第一大、世界第七大证券交易所。


Geography.

Xiangtan is located on the lower reaches of the Xiang River.

Etymology.

The name "Xiangtan" is derived from local geography, though there are several explanations for its origin vary somewhat in details. In any case, "Xiang" () refers to the Xiang River, while "Tan" () is a Chinese term that means "deep pool", specifically one produced by a moving current or waterfall; "Tan" in rivers generally are places where the current eddies. One reasoning is that the city was built by a large eddy in a bend of the Xiang River, and was thus called "Xiang-Tan". Another more likely story says the name originated in the Xiangzhou Eddy, today called the Zhao Eddy (). The Zhao Eddy is an ancient whirlpool located in a deep section of the Xiang River near the traditional border between Xiangtan and Changsha, and is named for King Zhao of Zhou, who is said to have died there.

History.

Pre-Ming Dynasty.

Relics from the Daxi culture indicate that people inhabited the Xiangtan area in the 3rd millennium BC. Shang Dynasty bronzewares have been found in the region, as well as tombs from the Warring States period. During the Three Kingdoms Period, the kingdom of Eastern Wu built a city in the west of modern Xiangtan City and organized the Hengyang Commandery () around it. In 749, the Tang Dynasty organized the area as Xiangtan County, centered at modern Yisu River (). By the time of the Northern Song Dynasty, Xiangtan's good access to both land and water trade routes had established it as the major commercial center of the region.

Ming and Qing Dynasties.

Xiangtan prospered throughout the Ming Dynasty and Qing Dynasty upon an economic foundation of trading in rice and traditional Chinese medicinal ingredients, and was sometimes referred to as "Little Nanjing" or "Golden Xiangtan". Prior to the Second Opium War, Xiangtan was a central transfer point for import and export goods going to and from ports in Canton, Shanghai, and Wuhan, supported by approximately 200,000 inhabitants.

Population.

As of 2010, Xiangtan had 2,748,552 inhabitants, of whom 1,877,919 lived in the built-up area (2 urban districts plus Xiangtan county). Together with the four adjoining urban districts of Zhuzhou, its built-up area is home to 2,933,069 inhabitants. In 2007, the city was named China's top ten livable cities by Chinese Cities Brand Value Report, which was released at the 2007 Beijing Summit of China Cities Forum.

Geography and climate.

Xiangtan has a humid subtropical climate with long, hot summers, and cool to cold, cloudy, damp winters with occasional snow flurries. Within its administrative area, the annual mean temperature is, with the coolest month being January, which averages, and the hottest July, at.

Administrative divisions.

The city of Xiangtan has direct jurisdiction over two districts (), two county-level cities (), and one county () :

Economy.

In 2006, Xiangtan's nominal GDP was ¥42.2 billion (US$6.2 billion), a year-on-year growth of 13.2% from the previous year. Its per capita GDP was ¥15,455 (US$2,265).  Xiangtan is famous for its production of Lotus seed and Soy sauce. People in Xiangtan like to chew areca nut (), though the area itself doesn't grow them. Most raw areca nut fruits are from Hainan and processed locally. The history of consuming areca nut dates back to 400 years ago, when people chewed it for pandemic prevention. Nowadays, it is quite common to see people chewing areca nut in Hunan. In 2003, the sales revenue of areca nut industry in Xiangtan had reached ¥800 million.

Government.

The current CPC Party Secretary of Xiangtan is Cao Jiongfang and the current Mayor is Zhang Yingchun.

Transportation.

Xiangtan is well connected by roads, river and rail. There is a shuttle bus service connecting to Changsha Huanghua International Airport.

Tourism.

Many people continue to visit Shaoshan, Xiangtan to visit the birthplace of Mao Zedong, the former Chairman of the Communist Party of China and the paramount leader of the People's Republic of China from 1949–1976.  Some local people like to visit zhaoshan, a small mountain surrounded by trees in Xiangtan.

Sports.

Professional tennis player Peng Shuai was born and trained in Xiangtan. Xiangtan Stadium was the home to Bayi Football Team of the Chinese Football Association Jia League (now Chinese Super League) from 2002 to 2003.

Colleges and universities.

This is a list of institutions with full-time bachelor programs in Xiangtan:

Notable locals.

Xiangtan is the birthplace of:

Xiangtan () is a prefecture-level city in the central part of Hunan province, China. The hometowns of several founding leaders of the Chinese Communist Party, including Chairman Mao Zedong, President Liu Shaoqi, and Marshal Peng Dehuai, are in Xiangtan's administration, as well as the hometowns of Qing dynasty painter Qi Baishi, scholar-general Zeng Guofan, and tennis player Peng Shuai.

湘潭市,简称潭,是中华人民共和国湖南省下辖的地级市,位于湖南省中部偏东,因盛产湘莲而得别名“莲城”。市境北临长沙市,东界株洲市,南接衡阳市,西连娄底市。地处湘中低山丘陵区,衡山北麓。湘江流经市境东北角并穿越市区,其支流涓水、涟水自西向东流贯汇入湘江。全市总面积5,006平方公里,2018年末市常驻人口286.5万,市人民政府驻岳塘区。狭义的湘潭,即是指“湘潭市区”,建立于南宋以后的湘潭县城的基础之上,曾作为“中国内地商埠之巨者”的商贸重镇,繁盛一时。现包括岳塘、雨湖2区,总面积658平方千米,其中建成区面积76平方千米;总人口约106万,其中城镇人口约96万,中国城市综合实力与竞争力百强,湖南省重要的工业、科技和旅游城市。是湖湘学派发源地、湖湘文化发源地,是长株潭城市群的中心城市之一,2007年被批准为全国资源节约型和环境友好型社会建设综合配套改革试验区。