Discovery.

The first descriptions of the MHC were made by British immunologist Peter Gorer in 1936. MHC genes were first identified in inbred mice strains. Clarence Little transplanted tumors across differing strains and found rejection of transplanted tumors according to strains of host versus donor. George Snell selectively bred two mouse strains, attained a new strain nearly identical to one of the progenitor strains, but differing crucially in histocompatibility—that is, tissue compatibility upon transplantation—and thereupon identified an MHC locus. Later Jean Dausset demonstrated the existence of MHC genes in human and described the first human leucocyte antigen, the protein which we call now HLA-A2. Some years later Baruj Benacerraf showed that polymorphic MHC genes not only determine an individual’s unique constitution of antigens but also regulate the interaction among the various cells of the immunological system. These three scientists have been awarded the Nobel Prize in Physiology or Medicine for 1980 for their discoveries concerning “genetically determined structures on the cell surface that regulate immunological reactions”.  The first fully sequenced and annotated MHC was published for humans in 1999 by a consortium of sequencing centers from UK, USA and Japan in "Nature". It was a "virtual MHC" since it was a mosaic from different individuals. A much shorter MHC locus from chickens was published in the same issue of "Nature". Many other species have been sequenced and the evolution of the MHC was studied, e.g. in the gray short-tailed opossum ("Monodelphis domestica"), a marsupial, MHC spans 3.95 Mb, yielding 114 genes, 87 shared with humans. Marsupial MHC genotypic variation lies between eutherian mammals and birds, taken as the minimal MHC encoding, but is closer in organization to that of nonmammals. The IPD-MHC Database was created which provides a centralised repository for sequences of the Major Histocompatibility Complex (MHC) from a number of different species. The database contains 77 species for the release from 2019-12-19.

Genes.

MHC locus is present in all jawed vertebrates, it is assumed to have arisen about 450 million years ago. Despite the difference in the number of genes included in MHC of different species, the overall organization of the locus is rather similar. Usual MHC contains about hundred genes and pseudogenes, not all of them are involved in the immunity. In humans, the MHC region occurs on chromosome 6, between the flanking genetic markers "MOG" and "COL11A2" (from 6p22.1 to 6p21.3 about 29Mb to 33Mb on the hg38 assembly), and contains 224 genes spanning 3.6 megabase pairs (3 600 000 bases). About half have known immune functions. The human MHC is also called the HLA (human leukocyte antigen) complex (often just the HLA). Similarly, there is SLA (Swine leukocyte antigens), BoLA (Bovine leukocyte antigens), DLA for dogs, etc. However, historically, the MHC in mice is called the Histocompatibility system 2 or just the H-2, in rats - RT1, and in chicken - B-locus.  The MHC gene family is divided into three subgroups: MHC class I, MHC class II, and MHC class III. Among all those genes present in MHC, there are two types of genes coding for the proteins MHC class I molecules and MHC class II molecules that directly involved in the antigen presentation. These genes are highly polymorphic, 19031 alleles of class I HLA, and 7183 of class II HLA are deposited for human in the data base IMGT.

Proteins.

MHC class I.

MHC class I molecules are expressed in all nucleated cells and also in platelets—in essence all cells but red blood cells. It presents epitopes to killer T cells, also called cytotoxic T lymphocytes (CTLs). A CTL expresses CD8 receptors, in addition to TCRs. When a CTL's CD8 receptor docks to a MHC class I molecule, if the CTL's TCR fits the epitope within the MHC class I molecule, the CTL triggers the cell to undergo programmed cell death by apoptosis. Thus, MHC class I helps mediate cellular immunity, a primary means to address intracellular pathogens, such as viruses and some bacteria, including bacterial L forms, bacterial genus "Mycoplasma", and bacterial genus "Rickettsia". In humans, MHC class I comprises HLA-A, HLA-B, and HLA-C molecules.  The first crystal structure of Class I MHC molecule, human HLA-A2, was published in 1989. The structure revealed that MHC-I molecules are heterodimers, they have polymorphic heavy α-subunit whose gene occurs inside the MHC locus and small invariant β microglobulin subunit whose gene is located usually outside of it. Polymorphic heavy chain of MHC-I molecule contains N-terminal extra-cellular region composed by three domains, α1, α2, and α3, transmembrane helix to hold MHC-I molecule on the cell surface and short cytoplasmic tail. Two domains, α1 and α2 form deep peptide-binding groove between two long α-helices and the floor of the groove formed by eight β-strands. Immunoglobulin-like domain α3 involved in the interaction with CD8 co-receptor. β microglobulin provides stability of the complex and participates in the recognition of peptide-MHC class I complex by CD8 co-receptor. The peptide is non-covalently bound to MHC-I, it is held by the several pockets on the floor of the peptide-binding groove. Amino acid side-chains that are most polymorphic in human alleles fill up the central and widest portion of the binding groove, while conserved side-chains are clustered at the narrower ends of the groove. Classical MHC molecules present epitopes to the TCRs of CD8+ T lymphocytes. Nonclassical molecules (MHC class IB) exhibit limited polymorphism, expression patterns, and presented antigens; this group is subdivided into a group encoded within MHC loci (e.g., HLA-E, -F, -G), as well as those not (e.g., stress ligands such as ULBPs, Rae1, and H60); the antigen/ligand for many of these molecules remain unknown, but they can interact with each of CD8+ T cells, NKT cells, and NK cells.

MHC Class II.

MHC class II can be conditionally expressed by all cell types, but normally occurs only on "professional" antigen-presenting cells (APCs): macrophages, B cells, and especially dendritic cells (DCs). An APC takes up an antigenic protein, performs antigen processing, and returns a molecular fraction of it—a fraction termed the epitope—and displays it on the APC's surface coupled within an MHC class II molecule (antigen presentation). On the cell's surface, the epitope can be recognized by immunologic structures like T cell receptors (TCRs). The molecular region which binds to the epitope is the paratope.  On surfaces of helper T cells are CD4 receptors, as well as TCRs. When a naive helper T cell's CD4 molecule docks to an APC's MHC class II molecule, its TCR can meet and bind the epitope coupled within the MHC class II. This event primes the naive T cell. According to the local milieu, that is, the balance of cytokines secreted by APCs in the microenvironment, the naive helper T cell (Th) polarizes into either a memory Th cell or an effector Th cell of phenotype either type 1 (Th), type 2 (Th), type 17 (Th), or regulatory/suppressor (T), as so far identified, the Th cell's terminal differentiation.  MHC class II thus mediates immunization to—or, if APCs polarize Th cells principally to T cells, immune tolerance of—an antigen. The polarization during primary exposure to an antigen is key in determining a number of chronic diseases, such as inflammatory bowel diseases and asthma, by skewing the immune response that memory Th cells coordinate when their memory recall is triggered upon secondary exposure to similar antigens. B cells express MHC class II to present antigens to Th, but when their B cell receptors bind matching epitopes, interactions which are not mediated by MHC, these activated B cells secrete soluble immunoglobulins: antibody molecules mediating humoral immunity.  Class II MHC molecules are also heterodimers, genes for both α and β subunits are polymorphic and located within MHC class II subregion. Peptide-binding groove of MHC-II molecules is forms by N-terminal domains of both subunits of the heterodimer, α1 and β1, unlike MHC-I molecules, where two domains of the same chain are involved. In addition, both subunits of MHC-II contain transmembrane helix and immunoglobulin domains α2 or β2 that can be recognized by CD4 co-receptors. In this way MHC molecules chaperone which type of lymphocytes may bind to the given antigen with high affinity, since different lymphocytes express different T-Cell Receptor (TCR) co-receptors.  MHC class II molecules in humans have five to six isotypes. Classic molecules present peptides to CD4+ lymphocytes. Nonclassic molecules, accessories, with intracellular functions, are not exposed on cell membranes, but in internal membranes in lysosomes, normally loading the antigenic peptides onto classic MHC class II molecules.

Class III.

Class III molecules have physiologic roles unlike classes I and II, but are encoded between them in the short arm of human chromosome 6. Class III molecules include several secreted proteins with immune functions: components of the complement system (such as C2, C4, and B factor), cytokines (such as TNF-α, LTA, and LTB), and heat shock proteins.

Function.

MHC is the tissue-antigen that allows the immune system (more specifically T cells) to bind to, recognize, and tolerate itself (autorecognition). MHC is also the chaperone for intracellular peptides that are complexed with MHCs and presented to T cell receptors (TCRs) as potential foreign antigens. MHC interacts with TCR and its co-receptors to optimize binding conditions for the TCR-antigen interaction, in terms of antigen binding affinity and specificity, and signal transduction effectiveness.  Essentially, the MHC-peptide complex is a complex of auto-antigen/allo-antigen. Upon binding, T cells should in principle tolerate the auto-antigen, but activate when exposed to the allo-antigen. Disease states occur when this principle is disrupted.  Antigen presentation: MHC molecules bind to both T cell receptor and CD4/CD8 co-receptors on T lymphocytes, and the antigen epitope held in the peptide-binding groove of the MHC molecule interacts with the variable Ig-Like domain of the TCR to trigger T-cell activation  Autoimmune reaction: Having some MHC molecules increases the risk of autoimmune diseases more than having others. HLA-B27 is an example. It is unclear how exactly having the HLA-B27 tissue type increases the risk of ankylosing spondylitis and other associated inflammatory diseases, but mechanisms involving aberrant antigen presentation or T cell activation have been hypothesized.  Tissue allorecognition: MHC molecules in complex with peptide epitopes are essentially ligands for TCRs. T cells become activated by binding to the peptide-binding grooves of any MHC molecule that they were not trained to recognize during positive selection in the thymus.

Antigen processing and presentation.

Peptides are processed and presented by two classical pathways:

T lymphocyte recognition restrictions.

In their development in the thymus, T lymphocytes are selected to recognize MHC molecules of the host, but not recognize other self antigens. Following selection, each T lymphocyte shows dual specificity: The TCR recognizes self MHC, but only non-self antigens.  MHC restriction occurs during lymphocyte development in the thymus through a process known as positive selection. T cells that do not receive a positive survival signal — mediated mainly by thymic epithelial cells presenting self peptides bound to MHC molecules — to their TCR undergo apoptosis. Positive selection ensures that mature T cells can functionally recognize MHC molecules in the periphery (i.e. elsewhere in the body).  The TCRs of T lymphocytes recognise only sequential epitopes, also called linear epitopes, of only peptides and only if coupled within an MHC molecule. (Antibody molecules secreted by activated B cells, though, recognize diverse epitopes—peptide, lipid, carbohydrate, and nucleic acid—and recognize conformational epitopes, which have three-dimensional structure.)

In sexual mate selection.

MHC molecules enable immune system surveillance of the population of protein molecules in a host cell, and greater MHC diversity permits greater diversity of antigen presentation. In 1976, Yamazaki "et al" demonstrated a sexual selection mate choice by male mice for females of a different MHC. Similar results have been obtained with fish. Some data find lower rates of early pregnancy loss in human couples of dissimilar MHC genes.  MHC may be related to mate choice in some human populations, a theory that found support by studies by Ober and colleagues in 1997, as well as by Chaix and colleagues in 2008. However, the latter findings have been controversial. If it exists, the phenomenon might be mediated by olfaction, as MHC phenotype appears strongly involved in the strength and pleasantness of perceived odour of compounds from sweat. Fatty acid esters—such as methyl undecanoate, methyl decanoate, methyl nonanoate, methyl octanoate, and methyl hexanoate—show strong connection to MHC.  In 1995, Claus Wedekind found that in a group of female college students who smelled T-shirts worn by male students for two nights (without deodorant, cologne, or scented soaps), by far most women chose shirts worn by men of dissimilar MHCs, a preference reversed if the women were on oral contraceptives. Results of a 2002 experiment likewise suggest HLA-associated odors influence odor preference and may mediate social cues. In 2005 in a group of 58 subjects, women were more indecisive when presented with MHCs like their own, although with oral contraceptives, the women showed no particular preference. No studies show the extent to which odor preference determines mate selection (or vice versa).

Evolutionary diversity.

Most mammals have MHC variants similar to those of humans, who bear great allelic diversity, especially among the nine classical genes—seemingly due largely to gene duplication—though human MHC regions have many pseudogenes. The most diverse loci, namely HLA-A, HLA-B, and HLA-C, have roughly 6000, 7200, and 5800 known alleles, respectively. Many HLA alleles are ancient, sometimes of closer homology to a chimpanzee MHC alleles than to some other human alleles of the same gene.  MHC allelic diversity has challenged evolutionary biologists for explanation. Most posit balancing selection (see polymorphism (biology)), which is any natural selection process whereby no single allele is absolutely most fit, such as frequency-dependent selection and heterozygote advantage. Pathogenic coevolution, as a type of balancing selection, posits that common alleles are under greatest pathogenic pressure, driving positive selection of uncommon alleles—moving targets, so to say, for pathogens. As pathogenic pressure on the previously common alleles decreases, their frequency in the population stabilizes, and remain circulating in a large population. Genetic drift is also a major driving force in some species. It is possible that the combined effects of some or all of these factors cause the genetic diversity.  MHC diversity has also been suggested as a possible indicator for conservation, because large, stable populations tend to display greater MHC diversity, than smaller, isolated populations. Small, fragmented populations that have experienced a population bottleneck typically have lower MHC diversity. For example, relatively low MHC diversity has been observed in the cheetah ("Acinonyx jubatus"), Eurasian beaver ("Castor fiber"), and giant panda ("Ailuropoda melanoleuca"). In 2007 low MHC diversity was attributed a role in disease susceptibility in the Tasmanian devil ("Sarcophilus harrisii"), native to the isolated island of Tasmania, such that an antigen of a transmissible tumor, involved in devil facial tumour disease, appears to be recognized as a "self antigen". To offset inbreeding, efforts to sustain genetic diversity in populations of endangered species and of captive animals have been suggested.  The MHC locus (6p21.3) has 3 other paralogous loci in the human genome, namely 19pl3.1, 9q33-q34, and 1q21-q25. It is believed that the loci arouse from the two-round duplications in vertebrates of a single ProtoMHC locus, and the new domain organizations of the MHC genes were a result of later cis-duplication and exon shuffling in a process termed "the MHC Big Bang." Genes in this locus are apparently linked to intracellular intrinsic immunity in the basal Metazoan "Trichoplax adhaerens".

In transplant rejection.

In a transplant procedure, as of an organ or stem cells, MHC molecules act themselves as antigens and can provoke immune response in the recipient, thus causing transplant rejection. MHC molecules were identified and named after their role in transplant rejection between mice of different strains, though it took over 20 years to clarify MHC's role in presenting peptide antigens to cytotoxic T lymphocytes (CTLs).  Each human cell expresses six MHC class I alleles (one HLA-A, -B, and -C allele from each parent) and six to eight MHC class II alleles (one HLA-DP and -DQ, and one or two HLA-DR from each parent, and combinations of these). The MHC variation in the human population is high, at least 350 alleles for HLA-A genes, 620 alleles for HLA-B, 400 alleles for DR, and 90 alleles for DQ. Any two individuals who are not identical twins will express differing MHC molecules. All MHC molecules can mediate transplant rejection, but HLA-C and HLA-DP, showing low polymorphism, seem least important.  When maturing in the thymus, T lymphocytes are selected for their TCR incapacity to recognize self antigens, yet T lymphocytes can react against the donor MHC's peptide-binding groove, the variable region of MHC holding the presented antigen's epitope for recognition by TCR, the matching paratope. T lymphocytes of the recipient take the incompatible peptide-binding groove as nonself antigen. The T lymphocytes' recognition of the foreign MHC as self is allorecognition.  Transplant rejection has various types known to be mediated by MHC (HLA):  In all of the above situations, immunity is directed at the transplanted organ, sustaining lesions. A cross-reaction test between potential donor cells and recipient serum seeks to detect presence of preformed anti-HLA antibodies in the potential recipient that recognize donor HLA molecules, so as to prevent hyperacute rejection. In normal circumstances, compatibility between HLA-A, -B, and -DR molecules is assessed. The higher the number of incompatibilities, the lower the five-year survival rate. Global databases of donor information enhance the search for compatible donors.

HLA biology.

Human MHC class I and II are also called human leukocyte antigen (HLA). To clarify the usage, some of the biomedical literature uses HLA to refer specifically to the HLA protein molecules and reserves MHC for the region of the genome that encodes for this molecule, but this is not a consistent convention.  The most studied HLA genes are the nine classical MHC genes: "HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA", and "HLA-DRB1". In humans, the MHC gene cluster is divided into three regions: classes I, II, and III. The A, B and C genes belong to MHC class I, whereas the six D genes belong to class II.  MHC alleles are expressed in codominant fashion. This means the alleles (variants) inherited from both parents are expressed equally:  The set of alleles that is present in each chromosome is called the MHC haplotype. In humans, each HLA allele is named with a number. For instance, for a given individual, his haplotype might be HLA-A2, HLA-B5, HLA-DR3, etc... Each heterozygous individual will have two MHC haplotypes, one each from the paternal and maternal chromosomes.  The MHC genes are highly polymorphic; many different alleles exist in the different individuals inside a population. The polymorphism is so high, in a mixed population (nonendogamic), no two individuals have exactly the same set of MHC molecules, with the exception of identical twins.  The polymorphic regions in each allele are located in the region for peptide contact. Of all the peptides that could be displayed by MHC, only a subset will bind strongly enough to any given HLA allele, so by carrying two alleles for each gene, a much larger set of peptides can be presented.  On the other hand, inside a population, the presence of many different alleles ensures there will always be an individual with a specific MHC molecule able to load the correct peptide to recognize a specific microbe. The evolution of the MHC polymorphism ensures that a population will not succumb to a new pathogen or a mutated one, because at least some individuals will be able to develop an adequate immune response to win over the pathogen. The variations in the MHC molecules (responsible for the polymorphism) are the result of the inheritance of different MHC molecules, and they are not induced by recombination, as it is the case for the antigen receptors.  Because of the high levels of allelic diversity found within its genes, MHC has also attracted the attention of many evolutionary biologists.

The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. This locus got its name because it was discovered in the study of tissue compatibility upon transplantation. Later studies revealed that tissue rejection due to incompatibility is an experimental artifact masking the real function of MHC molecules - binding an antigen derived from self-proteins or from pathogen and the antigen presentation on the cell surface for recognition by the appropriate T-cells. MHC molecules mediate interactions of leukocytes, also called white blood cells (WBCs), which are immune cells, with other leukocytes or with body cells. The MHC determines compatibility of donors for organ transplant, as well as one's susceptibility to an autoimmune disease via cross-reacting immunization.

Hlavní histokompatibilní komplex (MHC, z angl. major histocompatibility complex) je označení pro několik typů glykoproteinových komplexů nacházejících se na vnějších stranách cytoplazmatické membrány buněk obratlovců. Mají významnou funkci v imunitním systému, konkrétně se podílejí na rozeznávání cizorodých struktur (například virových bílkovin, jež značí infekci). MHC totiž slouží jako jakési „podstavce“, na něž se upevňují náhodně vybrané peptidy pocházející zevnitř buňky a vystavují se ke kontrole buňkám imunitního systému.


Early reign as Duke of Upper Bavaria.

Louis was born in Munich, the son of Louis II, Duke of Upper Bavaria and Count Palatine of the Rhine, and Matilda, a daughter of King Rudolph I.  Though Louis was partly educated in Vienna and became co-regent of his brother Rudolf I in Upper Bavaria in 1301 with the support of his Habsburg mother and her brother, King Albert I, he quarrelled with the Habsburgs from 1307 over possessions in Lower Bavaria. A civil war against his brother Rudolf due to new disputes on the partition of their lands was ended in 1313, when peace was made at Munich.  In the same year, on November 9, Louis defeated his Habsburg cousin Frederick the Fair who was further aided by duke Leopold I. Originally, he was a friend of Frederick, with whom he had been raised. However, armed conflict arose when the guardianship over the young Dukes of Lower Bavaria (Henry XIV, Otto IV, and Henry XV) was entrusted to Frederick, even though the late Duke Otto III, the former King of Hungary, had chosen Louis. On 9 November 1313, Frederick was defeated by Louis in the Battle of Gammelsdorf and had to renounce the tutelage. This victory caused a stir within the Holy Roman Empire and increased the reputation of the Bavarian Duke.

Election as German King and conflict with Habsburg.

The death of Holy Roman Emperor Henry VII in August 1313 necessitated the election of a successor. Henry's son John, King of Bohemia since 1310, was considered by many prince-electors to be too young, and by others to be already too powerful. One alternative was Frederick the Fair, the son of Henry's predecessor, Albert I, of the House of Habsburg. In reaction, the pro-Luxembourg party among the prince electors settled on Louis as its candidate to prevent Frederick's election.  On 19 October 1314, Archbishop Henry II Cologne chaired an assembly of four electors at Sachsenhausen, south of Frankfurt. Participants were Louis' brother, Rudolph I of the Palatinate, who objected to the election of his younger brother, Duke Rudolph I of Saxe-Wittenberg, and Henry of Carinthia, whom the Luxembourgs had deposed as King of Bohemia. These four electors chose Frederick as King.  The Luxembourg party did not accept this election and the next day a second election was held. Upon the instigation of Peter of Aspelt, Archbishop of Mainz, five different electors convened at Frankfurt and elected Louis as King. These electors were Archbishop Peter himself, Archbishop Baldwin of Trier and King John of Bohemia - both of the House of Luxembourg - Margrave Waldemar of Brandenburg and Duke John II of Saxe-Lauenburg, who contested Rudolph of Wittenberg's claim to the electoral vote.  This double election was quickly followed by two coronations: Louis was crowned at Aachen - the customary site of coronations - by Archbishop Peter of Mainz, while the Archbishop of Cologne, who by custom had the right to crown the new king, crowned Frederick at Bonn. In the following conflict between the kings, Louis recognized in 1316 the independence of Switzerland from the Habsburg dynasty.  After several years of bloody war, victory finally seemed within the grasp of Frederick, who was strongly supported by his brother Leopold. However, Frederick's army was decisively defeated in the Battle of Mühldorf on 28 September 1322 on the Ampfing Heath, where Frederick and 1300 nobles from Austria and Salzburg were captured.  Louis held Frederick captive in Trausnitz Castle (Schwandorf) for three years, but the determined resistance by Frederick's brother Leopold, the retreat of John of Bohemia from his alliance, and the Pope's ban induced Louis to release Frederick in the Treaty of Trausnitz of 13 March 1325. In this agreement, Frederick recognized Louis as legitimate ruler and undertook to return to captivity if he did not succeed in convincing his brothers to submit to Louis.  As he did not manage to overcome Leopold's obstinacy, Frederick returned to Munich as a prisoner, even though the Pope had released him from his oath. Louis, who was impressed by such nobility, renewed the old friendship with Frederick, and they agreed to rule the Empire jointly. Since the Pope and the electors strongly objected to this agreement, another treaty was signed at Ulm on 7 January 1326, according to which Frederick would administer Germany as King of the Romans, while Louis would be crowned as Holy Roman Emperor in Italy. However, after Leopold's death in 1326, Frederick withdrew from the regency of the Empire and returned to rule only Austria. He died on 13 January 1330.  Despite Louis' victory, Pope John XXII still refused to ratify his election, and in 1324 he excommunicated Louis, but the sanction had less effect than in earlier disputes between emperors and the papacy.

Coronation as Holy Roman Emperor and conflict with the Pope.

After the reconciliation with the Habsburgs in 1326, Louis marched to Italy and was crowned King of Italy in Milan in 1327. Already in 1323, Louis had sent an army to Italy to protect Milan against the Kingdom of Naples, which was together with France the strongest ally of the papacy. But now the Lord of Milan Galeazzo I Visconti was deposed since he was suspected of conspiring with the pope.  In January 1328, Louis entered Rome and had himself crowned emperor by the aged senator Sciarra Colonna, called "captain of the Roman people". Three months later, Louis published a decree declaring Pope John XXII ("Jacques Duèze") deposed on grounds of heresy. He then installed a Spiritual Franciscan, Pietro Rainalducci as Nicholas V, but both left Rome in August 1328. In the meantime, Robert, King of Naples had sent both a fleet and an army against Louis and his ally Frederick II of Sicily. Louis spent the winter 1328/29 in Pisa and stayed then in Northern Italy until his co-ruler Frederick of Habsburg had died. In fulfillment of an oath, Louis founded Ettal Abbey on 28 April 1330 on his return from Italy. Franciscan theologians Michael of Cesena and William of Ockham, and the philosopher Marsilius of Padua, who were all on bad terms with the Pope as well, joined Emperor Louis in Italy and accompanied him to his court at Alter Hof in Munich which became the first imperial residence of the Holy Roman Empire.  In 1333, Emperor Louis sought to counter French influence in the southwest of the empire so he offered Humbert II of Viennois the Kingdom of Arles which was an opportunity to gain full authority over Savoy, Provence, and its surrounding territories. Humbert was reluctant to take the crown due to the conflict that would follow with all around him, so he declined, telling the emperor that he should make peace with the church first.  Emperor Louis also allied with King Edward III of England in 1337 against King Philip VI of France, the protector of the new Pope Benedict XII in Avignon. King Philip VI had prevented any agreement between the Emperor and the Pope. Thus, the failure of negotiations with the papacy led to the declaration at Rhense in 1338 by six electors to the effect that election by all or the majority of the electors automatically conferred the royal title and rule over the empire, without papal confirmation. King Edward III was the Emperor's guest at the Imperial Diet in the Kastorkirche at Coblence in 1338 and was named Vicar-General of the Holy Roman Empire. However in 1341, the Emperor deserted Edward III but came to terms with Philip VI only temporarily. For the expected English payments were missing and Louis intended to reach an agreement with the Pope one more time.

Imperial privileges.

Louis IV was a protector of the Teutonic Knights. In 1337 he allegedly bestowed upon the Teutonic Order a privilege to conquer Lithuania and Russia, although the Order had only petitioned for three small territories. Later he forbade the Order to stand trial before foreign courts in their territorial conflicts with foreign rulers.  Louis concentrated his energies also on the economic development of the cities of the empire, so his name can be found in many city chronicles for the privileges he granted. In 1330 the emperor for example permitted the Frankfurt Trade Fair, and in 1340 Lübeck, as the most powerful member of the future Hanseatic League, received the coinage prerogative for golden gulden.

Dynastic policy.

In 1323 Louis gave Brandenburg as a fiefdom to his eldest son Louis V after the Brandenburg branch of the House of Ascania had died out. With the Treaty of Pavia in 1329 the emperor reconciled the sons of his late brother Rudolph and returned the Palatinate to his nephews Rudolf and Rupert. After the death of Henry of Bohemia, the duchy of Carinthia was released as an imperial fief on 2 May 1335 in Linz to his Habsburg cousins Albert II, Duke of Austria, and Otto, Duke of Austria, while Tyrol was first placed into Luxemburg hands.  With the death of duke John I in 1340 Louis inherited Lower Bavaria and then reunited the duchy of Bavaria. John's mother, a member of the Luxemburg dynasty, had to return to Bohemia. In 1342 Louis also acquired Tyrol for the Wittelsbach by voiding the first marriage of Margarete Maultasch with John Henry of Bohemia and marrying her to his own son Louis V, thus alienating the House of Luxemburg even more.  In 1345 the emperor further antagonized the lay princes by conferring Hainaut, Holland, Zeeland, and Friesland upon his wife, Margaret II of Hainaut. The hereditary titles of Margaret's sisters, one of whom was the queen of England, were ignored. Because of the dangerous hostility of the Luxemburgs, Louis had increased his power base ruthlessly.

Conflict with Luxemburg.

The acquisition of these territories and his restless foreign policy had earned Louis many enemies among the German princes. In the summer of 1346 the Luxemburg Charles IV was elected rival king, with the support of Pope Clement VI. Louis himself obtained much support from the Imperial Free Cities and the knights and successfully resisted Charles, who was widely regarded as a papal puppet ("rex clericorum" as William of Ockham called him). Also the Habsburg dukes stayed loyal to Louis. In the Battle of Crécy Charles' father John of Luxemburg was killed; Charles himself also took part in the battle but escaped.  But then Louis' sudden death avoided a longer civil war. Louis died in October 1347 from a stroke suffered during a bear-hunt in Puch near Fürstenfeldbruck. He is buried in the Frauenkirche in Munich. The sons of Louis supported Günther von Schwarzburg as new rival king to Charles but finally joined the Luxemburg party after Günther's early death in 1349 and divided the Wittelsbach possessions amongst themselves again. In continuance of the conflict of the House of Wittelsbach with the House of Luxemburg, the Wittelsbach family returned to power in the Holy Roman Empire in 1400 with King Rupert of Germany, a great-grandnephew of Louis.

Family and children.

In 1308 Louis IV married his first wife, Beatrix of Świdnica (1290-1320). Their children were:  In 1324 he married his second wife, Margaret II, Countess of Hainaut and Holland (1308-1356). Their children were:

Louis IV (; 1 April 1282 – 11 October 1347), called the Bavarian, of the house of Wittelsbach, was King of the Romans from 1314, King of Italy from 1327, and Holy Roman Emperor from 1328.

Ludvík IV. Bavor ( "Ludwig IV. / Ludwig der Bayer", 1282/7 Heidelberg – 11. října 1347 Puch u Fürstenfeldbrucku) byl bavorský vévoda, falckrabě rýnský, od roku 1314 římský král a od roku 1328 také sporný císař Svaté říše římské. Znám je také jako Ludvík Bavor, ale toto označení mělo původně hanlivý nádech. Ludvíka IV. Bavorského nazval Ludvíkem Bavorem jeho odpůrce papež Jan XXII. ve slavném Sachsenhausenském odvolání z roku 1324. Ludvík Bavor totiž znělo v latině podobně jako "Ludvík Barbar" ("Ludovicus Bavarus – Ludovicus Barbarus").


Design.

The Uzi uses an open-bolt, blowback-operated design, quite similar to the Jaroslav Holeček-designed Czech ZK 476 (prototype only) and the production Sa 23, Sa 24, Sa 25, and Sa 26 series of submachine guns. The open bolt design exposes the breech end of the barrel, and improves cooling during periods of continuous fire. However, it means that since the bolt is held to the rear when cocked, the receiver is more susceptible to contamination from sand and dirt. It uses a telescoping bolt design, in which the bolt wraps around the breech end of the barrel. This allows the barrel to be moved far back into the receiver and the magazine to be housed in the pistol grip, allowing for a heavier, slower-firing bolt in a shorter, better-balanced weapon.  The weapon is constructed primarily from stamped sheet metal, making it less expensive per unit to manufacture than an equivalent design machined from forgings. With relatively few moving parts, the Uzi is easy to strip for maintenance or repair. The magazine is housed within the pistol grip, allowing for intuitive and easy reloading in dark or difficult conditions, under the principle of "hand finds hand". The pistol grip is fitted with a grip safety, making it difficult to fire accidentally. However, the protruding vertical magazine makes the gun awkward to fire when prone. The Uzi features a bayonet lug.

Operation.

The non-reciprocating charging handle on the top of the receiver cover is used to retract the bolt. Variants have a ratchet safety mechanism which will catch the bolt and lock its movement if it is retracted past the magazine, but not far enough to engage the sear. When the handle is fully retracted to the rear, the bolt will cock (catch) on the sear mechanism and the handle and cover are released to spring fully forward under power of a small spring. The cover will remain forward during firing since it does not reciprocate with the bolt. The military and police versions will fire immediately upon chambering a cartridge as the Uzi is an open bolt weapon.  There are two external safety mechanisms on the Uzi. The first is the three-position selector lever located at the top of the grip and behind the trigger group. The rear position is "S", or "safe" (S = Sicher or Secure on the MP2), which locks the sear and prevents movement of the bolt.  The second external safety mechanism is the grip safety, which is located at the rear of the grip. It is meant to help prevent accidental discharge if the weapon is dropped or the user loses a firm grip on the weapon during firing.  The trigger mechanism is a conventional firearm trigger, but functions only to control the release mechanism for either the bolt (submachine gun) or firing pin holding mechanism (semi-auto) since the Uzi does not incorporate an internal cocking or hammer mechanism. While the open-bolt system is mechanically simpler than a closed-bolt design (e.g. Heckler & Koch MP5), it creates a noticeable delay between when the trigger is pulled and when the gun fires.  The magazine release button or lever is located on the lower portion of the pistol grip and is intended to be manipulated by the non-firing hand. The paddle-like button lies flush with the pistol grip in order to help prevent accidental release of the magazine during rigorous or careless handling.  When the gun is de-cocked the ejector port closes, preventing entry of dust and dirt. Though the Uzi's stamped-metal receiver is equipped with pressed reinforcement slots to accept accumulated dirt and sand, the weapon can still jam with heavy accumulations of sand in desert combat conditions when not cleaned regularly. The magazine must be removed prior to de-cocking the weapon.

Stocks.

There are different stocks available for the Uzi proper. There is a wooden stock with a metal buttplate that comes in three similar variations that was used by the IDF. The first version had a flat butt and straight comb and had hollows for a cleaning rod and gun oil bottle. The second had an angled butt and a straight comb and no hollows. The third had an angled butt and curved comb and no hollows; a polymer version is currently available from IMI. The wooden stocks originally had a quick-release base but the ones sold in the United States have a permanent base to be compliant with US gun laws.  Choate made an aftermarket polymer stock with a rubber buttpad that had a flat butt, a straight comb, and a permanent base.  In 1956, IMI developed a downward-folding twin-strut metal stock with two swiveling sections that tucks under the rear of the receiver. The Mini Uzi has a forward-folding single-strut metal stock that is actually an inch longer than the Uzi's. Its buttplate can be used as a foregrip when stowed. The Micro Uzi has a similar model.

Magazines.

The original box magazines for the 9mm Uzi had a 25-round capacity. Experimental 40- and 50-round extended magazines were tried but were found to be unreliable. A 32-round extended magazine was then tried and was later accepted as standard. The Mini Uzi and Micro Uzi use a shorter 20-round magazine. Available extended magazines include 40-, and 50-round magazines. Other high-capacity aftermarket magazines exist such as the Vector Arms 70-round and Beta Company (Beta C-Mag) 100-round drums.  The.45 ACP Uzi used a 16- or 22-round magazine, while the.45 ACP Micro Uzi and Mini Uzi used a 12-round magazine. A conversion kit by Vector Arms allowed the.45-caliber Uzi to use the same 30-round magazines as the M3 "Grease Gun".

Caliber conversions.

The Uzi was available with caliber conversion kits in.22 LR or.41 AE. The operator just has to change the barrel, bolt and magazine. The.22 LR had 20-round magazines; the original IMI kit used a barrel insert while the aftermarket Action Arms kit used a full replacement barrel. The.41 AE also had a 20-round magazine; since it has the same bolt face as the 9×19mm Parabellum, only the barrel and magazine needed to be changed.  IMI also manufactured a.45ACP conversion kit both in full auto/open bolt with a 10.2" barrel for the 9mm SMG and a semi only/closed bolt with a 16" barrel for the carbine version. Magazine capacity is limited, with 2 sizes of 16 and 10 rds each.

Operational use.

The Uzi submachine gun was designed by Captain (later Major) Uziel Gal of the Israel Defense Forces (IDF) following the 1948 Arab–Israeli War. The weapon was submitted to the Israeli Army for evaluation and won out over more conventional designs due to its simplicity and economy of manufacture. Gal did not want the weapon to be named after him, but his request was ignored. The Uzi was officially adopted in 1951. First introduced to IDF special forces in 1954, the weapon was placed into general issue two years later. The first Uzis were equipped with a short, fixed wooden buttstock, and this is the version that initially saw combat during the 1956 Suez Campaign. Later models would be equipped with a folding metal stock.  The Uzi was used as a personal defense weapon by rear-echelon troops, officers, artillery troops and tankers, as well as a frontline weapon by elite light infantry assault forces. The Uzi's compact size and firepower proved instrumental in clearing Syrian bunkers and Jordanian defensive positions during the 1967 Six-Day War. Though the weapon was phased out of frontline IDF service in the 1980s, some Uzis and Uzi variants were still used by a few IDF units until December 2003, when the IDF announced that it was retiring the Uzi from all IDF forces. It was subsequently replaced by the fully automatic Micro Tavor.  In general, the Uzi was a reliable weapon in military service. However, even the Uzi fell victim to extreme conditions of sand and dust. During the Sinai Campaign of the Yom Kippur War, IDF Army units reaching the Suez Canal reported that of all their small arms, only the 7.62 mm FN MAG machine gun was still in operation.  The Uzi proved especially useful for mechanized infantry needing a compact weapon, and for infantry units clearing bunkers and other confined spaces. However, its limited range and accuracy in automatic fire (approximately 50 m) could be disconcerting when encountering enemy forces armed with longer-range small arms, and heavier support weapons could not always substitute for a longer-ranged individual weapon. These failings eventually caused the phasing out of the Uzi from IDF front-line assault units.  The Uzi has been used in various conflicts outside Israel and the Middle East during the 1960s and 1970s. Quantities of 9 mm Uzi submachine guns were used by Portuguese cavalry, police, and security forces during the Portuguese Colonial Wars in Africa.

Worldwide sales.

Total sales of the weapon to date (end 2001) has netted IMI over $2 billion (US), with over 90 countries using the weapons either for their armed forces or in law enforcement.

Military variants.

The Uzi Submachine Gun is a standard Uzi with a barrel. It has a rate of automatic fire of 600 rounds per minute (rpm) when chambered in 9mm Parabellum; the.45 ACP model's rate of fire is slower at 500 rpm.  The Mini Uzi is a smaller version of the regular Uzi, first introduced in 1980. The Mini Uzi is 600 mm (23.62 inches) long or 360 mm (14.17 inches) long with the stock folded. Its barrel length is 197 mm (7.76 inches), its muzzle velocity is 375 m/s (1230 f/s) and its effective range is 100 m. It has a greater automatic rate of fire of 950 rounds per minute due to the shorter bolt. Its weight is approximately. The Micro Uzi is an even further scaled down version of the Uzi, introduced in 1986. The Micro Uzi is 486 mm (19.13 in) long, reduced to 282 mm (11.10 in) with the stock folded and its barrel length is 117 mm and has a closed bolt compared to its original counterpart. Its muzzle velocity is 350 m/s (1148 f/s) and its cyclic rate of fire is 1,200 rpm. It weighs slightly over.  The Uzi Pro, an improved variant of the Micro Uzi, was launched in 2010 by Israel Weapon Industries Ltd. (I.W.I.), formerly the "magen" ("small arms") division of Israel Military Industries. The Uzi Pro is a blowback-operated, select-fire, closed-bolt submachine gun with a large lower portion, comprising grip and handguard, entirely made of polymer to reduce weight; the grip section was redesigned to allow two-handed operation and facilitate control in full-automatic fire with such a small-sized firearm. The Uzi Pro features four Picatinny rails, two at the sides of the barrel, which can be removed, one below the barrel for the addition of forgrips and one on the top for optics. The under barrel rail is often shown with a specialised foregrip which attaches to the pistol grip to form a hand guard. In addition, the cocking handle has been moved to the left side. The new weapon weighs 2.32 kg and has a length of 529 mm with an extended stock, and 30 cm while collapsed. It has been purchased by the IDF in limited numbers for evaluation and it is yet to be decided whether or not to order additional units for all of its special forces.

Civilian variants.

Uzi carbine.

The Uzi carbine is similar in appearance to the Uzi submachine gun. The Uzi carbine is fitted with a 400-mm (16-inch) barrel, to meet the minimum rifle barrel length requirement for civilian sales in the United States. A small number of Uzi carbines were produced with the standard length barrel for special markets. It fires from a closed-bolt position in semi-automatic mode only and uses a floating firing pin as opposed to a fixed firing pin. The FS-style selector switch has two positions (the automatic setting was blocked): "F" for "fire" (semi-auto) and "S" for "safe". Uzi carbines are available in calibers.22LR, 9mm,.41 AE, and.45 ACP.  The Uzi carbine has two main variants, the Model A (imported from 1980 to 1983) and the Model B (imported from 1983 until 1989). The Type A was the same as the fully automatic Uzi, while the Type B had a firing pin safety and improved sights and sling swivels. These two variants were imported and distributed by Action Arms.  The American firm Group Industries made limited numbers of a copy of the Uzi "B" model semiauto carbine for sale in the US along with copies of the Uzi submachine gun for the U.S. collectors' market. After registering several hundred submachine guns transferable to the general public through a special government regulated process, production was halted due to financial troubles at the company. Company assets (including partially made Uzi submachine guns, parts, and tooling) were purchased by an investment group later to become known as Vector Arms. Vector Arms built and marketed numerous versions of the Uzi carbine and the Mini Uzi.  Today, while the civilian manufacture, sale and possession of post 1986 select-fire Uzi and its variants is prohibited in the United States it is still legal to sell templates, tooling and manuals to complete such conversion. These items are typically marketed as being "post-sample" materials for use by federal firearm licensees for manufacturing/distributing select-fire variants of the Uzi to Law Enforcement, Military and Overseas customers.

Mini Uzi carbine.

The Mini Uzi carbine is similar in appearance to the Mini Uzi machine pistol. The Mini Uzi carbine is fitted with a 500-mm (19.8-in) barrel, to meet the minimum rifle overall length requirement for civilian sales in the United States. It fires from a closed-bolt position in semi-automatic mode only.

Uzi pistol.

The Uzi pistol is a semi-automatic, closed bolt, and blowback-operated pistol variant. Its muzzle velocity is 345 m/s. It is a Micro Uzi with no shoulder stock or full-automatic firing capability. The intended users of the pistol are various security agencies in need of a high-capacity semi-automatic pistol, or civilian shooters who want a gun with those qualities and the familiarity of the Uzi style. It was introduced in 1984 and produced until 1993.

Uzi Pro pistol.

The Uzi Pro pistol is a current version of the Uzi pistol. It has rails on the top and bottom, and there is an optional stabilizing brace. Unlike any other Uzi variant, the Uzi Pro pistol has a side charging handle, rather than a top charging handle, and has a three-stage safety. There are three safeties on the Uzi Pro pistol: a thumb safety, grip safety, and a firing pin block. This model was intended for law enforcement and civilian use, due to the compact size, rails, and a semi-automatic rate of fire. Unlike other Uzi variants, the Uzi Pro pistol is only chambered for 9x19 parabellum.

Copies.

AG Strojnica ERO.

The "Arma Grupa" Strojnica ERO (Arms Group "ERO machine-gun") was a Croatian Uzi clone made locally by "Arma Grupa" of Zagreb during the Yugoslav War. It was made entirely from steel stampings, causing it to weigh more (). The only difference from the Uzi is the selector switch, which is marked R ("Rafalno" {"burst"}, for full automatic fire), P ("Pojedinačno", for single shot) and Z ("Zaključan",{locked}, for safe) and its rate of fire is 650 rounds per minute. It uses the 32-round magazine as standard, but can use any 9mm Uzi-interface magazine of 25 rounds or larger.  The Strojnica Mini ERO is a clone of the Micro Uzi; it differs in that it had a heavy-gauge folding wire stock like the Vz.61 "Skorpion" Machine Pistol. It weighs 2.2 kg / 4.85 lbs. unloaded and is 545.5 mm / 21.47 inches overall with the folding stock extended and 250 mm / 9.84 inches with the stock folded. It uses the 20-round Mini Uzi magazine.  The EROs were used by the Croatians as early as 1992.

BA93 and BA94.

The BA93 and BA94 are Burma-made clones of the Uzi. Production started in Myanmar after 1991 when an Israeli delegation visited the country and supplied the "Tatmadaw" with Uzis. It also included the rights to manufacture the Uzi under license.  The BA93 is based on the Uzi, but with a longer barrel and fixed stock. It was introduced in 1993. It's commonly seen with Myanma soldiers and special forces units operating in commando or VIP protection operations.  The BA94 was introduced in 1994. Improvements made include moving the charging handle from the top to the left with a shorter barrel. This model is mostly seen with Myanma police forces.  As of 2018, both weapons were renamed MA-13.

Norinco M320.

Norinco of China manufactures an unlicensed copy of the Uzi Model B that is sold as the M320. Early versions were marked "POLICE Model" in English. Modifications were made to avoid the US Assault Weapon Import Ban: the folding stock was replaced with a wooden thumbhole stock, the barrel nut was welded in place, and the bayonet lug was removed. The gun had a gray parkerized finish, a 410-mm (16-inch) carbine-length barrel and is 800 mm (31.49 inches) overall.

Zastava M97.

The Zastava M97 is a Serbian clone of the Mini Uzi. Two variants consist of the M97 with an 8" barrel and the M97K with a 6.5" barrel and no folding stock with a vertical foregrip permanent attached.

The Uzi (, officially cased as UZI) is a family of Israeli open-bolt, blowback-operated submachine guns. Smaller variants are often considered to be machine pistols. The Uzi was one of the first weapons to use a telescoping bolt design which allows the magazine to be housed in the pistol grip for a shorter weapon.

Jako Uzi se označuje několik podobných samopalů, původem z Izraele. První prototyp byl vyvinut na konci 40. let. Jeho konstruktérem byl izraelský důstojník Uziel Gal, po němž se samopal jmenuje. V 80. letech byly vyvinuty dva menší modely, Mini-Uzi a Micro-Uzi. Vyráběl se v licenci v Belgii a Německu. Dodnes se vyrábí v Izraeli, používá ho izraelská armáda a je oblíbenou zbraní mnoha teroristických skupin. Je často zaměňován s americkým samopalem Ingram MAC-10 a obecně lze říct, že mezi laiky je výraz UZI "Uzík", "Uzina" používán pro libovolný samopal se zásobníkem umístěným v pistolové rukojeti. Konstrukčně vychází z československého samopalu ZK476.


History.

A process of osmosis through semipermeable membranes was first observed in 1748 by Jean-Antoine Nollet. For the following 200 years, osmosis was only a phenomenon observed in the laboratory. In 1950, the University of California at Los Angeles first investigated desalination of seawater using semipermeable membranes. Researchers from both University of California at Los Angeles and the University of Florida successfully produced fresh water from seawater in the mid-1950s, but the flux was too low to be commercially viable until the discovery at University of California at Los Angeles by Sidney Loeb and Srinivasa Sourirajan at the National Research Council of Canada, Ottawa, of techniques for making asymmetric membranes characterized by an effectively thin "skin" layer supported atop a highly porous and much thicker substrate region of the membrane. John Cadotte, of FilmTec Corporation, discovered that membranes with particularly high flux and low salt passage could be made by interfacial polymerization of "m"-phenylene diamine and trimesoyl chloride. Cadotte's patent on this process was the subject of litigation and has since expired. Almost all commercial reverse-osmosis membrane is now made by this method. By the end of 2001, about 15,200 desalination plants were in operation or in the planning stages, worldwide.  In 1977 Cape Coral, Florida became the first municipality in the United States to use the RO process on a large scale with an initial operating capacity of 11.35 million liters (3 million US gal) per day. By 1985, due to the rapid growth in population of Cape Coral, the city had the largest low-pressure reverse-osmosis plant in the world, capable of producing 56.8 million liters (15 million US gal) per day (MGD).  Formally, reverse osmosis is the process of forcing a solvent from a region of high solute concentration through a semipermeable membrane to a region of low-solute concentration by applying a pressure in excess of the osmotic pressure. The largest and most important application of reverse osmosis is the separation of pure water from seawater and brackish waters; seawater or brackish water is pressurized against one surface of the membrane, causing transport of salt-depleted water across the membrane and emergence of potable drinking water from the low-pressure side.  The membranes used for reverse osmosis have a dense layer in the polymer matrix—either the skin of an asymmetric membrane or an interfacially polymerized layer within a thin-film-composite membrane—where the separation occurs. In most cases, the membrane is designed to allow only water to pass through this dense layer while preventing the passage of solutes (such as salt ions). This process requires that a high pressure be exerted on the high-concentration side of the membrane, usually 2–17 bar (30–250 psi) for fresh and brackish water, and 40–82 bar (600–1200 psi) for seawater, which has around 27 bar (390 psi) natural osmotic pressure that must be overcome. This process is best known for its use in desalination (removing the salt and other minerals from sea water to produce fresh water), but since the early 1970s, it has also been used to purify fresh water for medical, industrial and domestic applications.

Fresh water applications.

Drinking water purification.

Around the world, household drinking water purification systems, including a reverse osmosis step, are commonly used for improving water for drinking and cooking.  Such systems typically include a number of steps: The latest developments in the sphere include nano materials and membranes.  In some systems, the carbon prefilter is omitted, and a cellulose triacetate membrane is used. CTA (cellulose triacetate) is a paper by-product membrane bonded to a synthetic layer and is made to allow contact with chlorine in the water. These require a small amount of chlorine in the water source to prevent bacteria from forming on it. The typical rejection rate for CTA membranes is 85–95%.  The cellulose triacetate membrane is prone to rotting unless protected by chlorinated water, while the thin film composite membrane is prone to breaking down under the influence of chlorine. A thin film composite (TFC) membrane is made of synthetic material, and requires chlorine to be removed before the water enters the membrane. To protect the TFC membrane elements from chlorine damage, carbon filters are used as pre-treatment in all residential reverse osmosis systems. TFC membranes have a higher rejection rate of 95–98% and a longer life than CTA membranes.  Portable reverse osmosis water processors are sold for personal water purification in various locations. To work effectively, the water feeding to these units should be under some pressure (280 kPa (40 psi) or greater is the norm). Portable reverse osmosis water processors can be used by people who live in rural areas without clean water, far away from the city's water pipes. Rural people filter river or ocean water themselves, as the device is easy to use (saline water may need special membranes). Some travelers on long boating, fishing, or island camping trips, or in countries where the local water supply is polluted or substandard, use reverse osmosis water processors coupled with one or more ultraviolet sterilizers.  In the production of bottled mineral water, the water passes through a reverse osmosis water processor to remove pollutants and microorganisms. In European countries, though, such processing of natural mineral water (as defined by a European directive) is not allowed under European law. In practice, a fraction of the living bacteria can and do pass through reverse osmosis membranes through minor imperfections, or bypass the membrane entirely through tiny leaks in surrounding seals. Thus, complete reverse osmosis systems may include additional water treatment stages that use ultraviolet light or ozone to prevent microbiological contamination.  Membrane pore sizes can vary from 0.1 to 5,000 nm depending on filter type. Particle filtration removes particles of 1 μm or larger. Microfiltration removes particles of 50 nm or larger. Ultrafiltration removes particles of roughly 3 nm or larger. Nanofiltration removes particles of 1 nm or larger. Reverse osmosis is in the final category of membrane filtration, hyperfiltration, and removes particles larger than 0.1 nm.

Decentralized use: solar-powered reverse osmosis.

A solar-powered desalination unit produces potable water from saline water by using a photovoltaic system that converts solar power into the required energy for reverse osmosis. Due to the extensive availability of sunlight across different geographies, solar-powered reverse osmosis lends itself well to drinking water purification in remote settings lacking an electricity grid. Moreover, Solar energy overcomes the usually high-energy operating costs as well as greenhouse emissions of conventional reverse osmosis systems, making it a sustainable freshwater solution compatible to developing contexts. For example, a solar-powered desalination unit designed for remote communities has been successfully tested in the Northern Territory of Australia.  While the intermittent nature of sunlight and its variable intensity throughout the day makes PV efficiency prediction difficult and desalination during night time challenging, several solutions exist. For example, batteries, which provide the energy required for desalination in non-sunlight hours can be used to store solar energy in daytime. Apart from the use of conventional batteries, alternative methods for solar energy storage exist. For example, thermal energy storage systems solve this storage problem and ensure constant performance even during non-sunlight hours and cloudy days, improving overall efficiency.

Military use: the reverse osmosis water purification unit.

A reverse osmosis water purification unit (ROWPU) is a portable, self-contained water treatment plant. Designed for military use, it can provide potable water from nearly any water source. There are many models in use by the United States armed forces and the Canadian Forces. Some models are containerized, some are trailers, and some are vehicles unto themselves.  Each branch of the United States armed forces has their own series of reverse osmosis water purification unit models, but they are all similar. The water is pumped from its raw source into the reverse osmosis water purification unit module, where it is treated with a polymer to initiate coagulation. Next, it is run through a multi-media filter where it undergoes primary treatment by removing turbidity. It is then pumped through a cartridge filter which is usually spiral-wound cotton. This process clarifies the water of any particles larger than 5 μm and eliminates almost all turbidity.  The clarified water is then fed through a high-pressure piston pump into a series of vessels where it is subject to reverse osmosis. The product water is free of 90.00–99.98% of the raw water's total dissolved solids and by military standards, should have no more than 1000–1500 parts per million by measure of electrical conductivity. It is then disinfected with chlorine and stored for later use.  Within the United States Marine Corps, the reverse osmosis water purification unit has been replaced by both the Lightweight Water Purification System and Tactical Water Purification Systems. The Lightweight Water Purification Systems can be transported by Humvee and filter per hour. The Tactical Water Purification Systems can be carried on a Medium Tactical Vehicle Replacement truck, and can filter per hour.

Water and wastewater purification.

Rain water collected from storm drains is purified with reverse osmosis water processors and used for landscape irrigation and industrial cooling in Los Angeles and other cities, as a solution to the problem of water shortages.  In industry, reverse osmosis removes minerals from boiler water at power plants. The water is distilled multiple times. It must be as pure as possible so it does not leave deposits on the machinery or cause corrosion. The deposits inside or outside the boiler tubes may result in under-performance of the boiler, reducing its efficiency and resulting in poor steam production, hence poor power production at the turbine.  It is also used to clean effluent and brackish groundwater. The effluent in larger volumes (more than 500 m/day) should be treated in an effluent treatment plant first, and then the clear effluent is subjected to reverse osmosis system. Treatment cost is reduced significantly and membrane life of the reverse osmosis system is increased.  The process of reverse osmosis can be used for the production of deionized water.  Reverse osmosis process for water purification does not require thermal energy. Flow-through reverse osmosis systems can be regulated by high-pressure pumps. The recovery of purified water depends upon various factors, including membrane sizes, membrane pore size, temperature, operating pressure, and membrane surface area.  In 2002, Singapore announced that a process named NEWater would be a significant part of its future water plans. It involves using reverse osmosis to treat domestic wastewater before discharging the NEWater back into the reservoirs.

Food industry.

In addition to desalination, reverse osmosis is a more economical operation for concentrating food liquids (such as fruit juices) than conventional heat-treatment processes. Research has been done on concentration of orange juice and tomato juice. Its advantages include a lower operating cost and the ability to avoid heat-treatment processes, which makes it suitable for heat-sensitive substances such as the protein and enzymes found in most food products.  Reverse osmosis is extensively used in the dairy industry for the production of whey protein powders and for the concentration of milk to reduce shipping costs. In whey applications, the whey (liquid remaining after cheese manufacture) is concentrated with reverse osmosis from 6% total solids to 10–20% total solids before ultrafiltration processing. The ultrafiltration retentate can then be used to make various whey powders, including whey protein isolate. Additionally, the ultrafiltration permeate, which contains lactose, is concentrated by reverse osmosis from 5% total solids to 18–22% total solids to reduce crystallization and drying costs of the lactose powder.  Although use of the process was once avoided in the wine industry, it is now widely understood and used. An estimated 60 reverse osmosis machines were in use in Bordeaux, France, in 2002. Known users include many of the elite-classed growths (Kramer) such as Château Léoville-Las Cases in Bordeaux.

Maple syrup production.

In 1946, some maple syrup producers started using reverse osmosis to remove water from sap before the sap is boiled down to syrup. The use of reverse osmosis allows about 75–90% of the water to be removed from the sap, reducing energy consumption and exposure of the syrup to high temperatures. Microbial contamination and degradation of the membranes must be monitored.

Low alcohol beer.

When beer at normal alcohol concentration is subject to reverse osmosis, both water and alcohol pass across the membrane more readily than the other components, leaving a "beer concentrate". The concentrate is then diluted with fresh water to restore the non-volatile components to their original intensity.

Hydrogen production.

For small-scale hydrogen production, reverse osmosis is sometimes used to prevent formation of mineral deposits on the surface of electrodes.

Aquariums.

Many reef aquarium keepers use reverse osmosis systems for their artificial mixture of seawater. Ordinary tap water can contain excessive chlorine, chloramines, copper, nitrates, nitrites, phosphates, silicates, or many other chemicals detrimental to the sensitive organisms in a reef environment. Contaminants such as nitrogen compounds and phosphates can lead to excessive and unwanted algae growth. An effective combination of both reverse osmosis and deionization is the most popular among reef aquarium keepers, and is preferred above other water purification processes due to the low cost of ownership and minimal operating costs. Where chlorine and chloramines are found in the water, carbon filtration is needed before the membrane, as the common residential membrane used by reef keepers does not cope with these compounds.  Freshwater aquarists also use reverse osmosis systems to duplicate the very soft waters found in many tropical water bodies. Whilst many tropical fish can survive in suitably treated tap water, breeding can be impossible. Many aquatic shops sell containers of reverse osmosis water for this purpose.

Window cleaning.

An increasingly popular method of cleaning windows is the so-called "water-fed pole" system. Instead of washing the windows with detergent in the conventional way, they are scrubbed with highly purified water, typically containing less than 10 ppm dissolved solids, using a brush on the end of a long pole which is wielded from ground level. Reverse osmosis is commonly used to purify the water.

Landfill leachate purification.

Treatment with reverse osmosis is limited, resulting in low recoveries on high concentration (measured with electrical conductivity) and fouling of the RO membranes. Reverse osmosis applicability is limited by conductivity, organics, and scaling inorganic elements such as CaSO4, Si, Fe and Ba. Low organic scaling can use two different technologies, one is using spiral wound membrane type of module, and for high organic scaling, high conductivity and higher pressure (up to 90 bars) disc tube modules with reverse-osmosis membranes can be used. Disc tube modules were redesigned for landfill leachate purification, that is usually contaminated with high levels of organic material. Due to the cross-flow with high velocity it is given a flow booster pump, that is recirculating the flow over the same membrane surface between 1.5 and 3 times before it is released as a concentrate. High velocity is also good against membrane scaling and allows successful membrane cleaning.

Desalination.

Areas that have either no or limited surface water or groundwater may choose to desalinate. Reverse osmosis is an increasingly common method of desalination, because of its relatively low energy consumption.  In recent years, energy consumption has dropped to around 3 kWh/m, with the development of more efficient energy recovery devices and improved membrane materials. According to the International Desalination Association, for 2011, reverse osmosis was used in 66% of installed desalination capacity (0.0445 of 0.0674 km3/day), and nearly all new plants. Other plants mainly use thermal distillation methods: multiple-effect distillation and multi-stage flash.  Sea-water reverse-osmosis (SWRO) desalination, a membrane process, has been commercially used since the early 1970s. Its first practical use was demonstrated by Sidney Loeb from University of California at Los Angeles in Coalinga, California, and Srinivasa Sourirajan of National Research Council, Canada. Because no heating or phase changes are needed, energy requirements are low, around 3 kWh/m, in comparison to other processes of desalination, but are still much higher than those required for other forms of water supply, including reverse osmosis treatment of wastewater, at 0.1 to 1 kWh/m. Up to 50% of the seawater input can be recovered as fresh water, though lower recoveries may reduce membrane fouling and energy consumption.  Brackish water reverse osmosis refers to desalination of water with a lower salt content than sea water, usually from river estuaries or saline wells. The process is substantially the same as sea water reverse osmosis, but requires lower pressures and therefore less energy. Up to 80% of the feed water input can be recovered as fresh water, depending on feed salinity.  The Ashkelon sea water reverse osmosis desalination plant in Israel is the largest in the world. The project was developed as a build-operate-transfer by a consortium of three international companies: Veolia water, IDE Technologies, and Elran.  The typical single-pass sea water reverse osmosis system consists of:

Pretreatment.

Pretreatment is important when working with reverse osmosis and nanofiltration membranes due to the nature of their spiral-wound design. The material is engineered in such a fashion as to allow only one-way flow through the system. As such, the spiral-wound design does not allow for backpulsing with water or air agitation to scour its surface and remove solids. Since accumulated material cannot be removed from the membrane surface systems, they are highly susceptible to fouling (loss of production capacity). Therefore, pretreatment is a necessity for any reverse osmosis or nanofiltration system. Pretreatment in sea water reverse osmosis systems has four major components:

High pressure pump.

The high pressure pump supplies the pressure needed to push water through the membrane, even as the membrane rejects the passage of salt through it. Typical pressures for brackish water range from 1.6 to 2.6 MPa (225 to 376 psi). In the case of seawater, they range from 5.5 to 8 MPa (800 to 1,180 psi). This requires a large amount of energy. Where energy recovery is used, part of the high pressure pump's work is done by the energy recovery device, reducing the system energy inputs.

Membrane assembly.

The membrane assembly consists of a pressure vessel with a membrane that allows feedwater to be pressed against it. The membrane must be strong enough to withstand whatever pressure is applied against it. Reverse-osmosis membranes are made in a variety of configurations, with the two most common configurations being spiral-wound and hollow-fiber.  Only a part of the saline feed water pumped into the membrane assembly passes through the membrane with the salt removed. The remaining "concentrate" flow passes along the saline side of the membrane to flush away the concentrated salt solution. The percentage of desalinated water produced versus the saline water feed flow is known as the "recovery ratio". This varies with the salinity of the feed water and the system design parameters: typically 20% for small seawater systems, 40% – 50% for larger seawater systems, and 80% – 85% for brackish water. The concentrate flow is at typically only 3 bar / 50 psi less than the feed pressure, and thus still carries much of the high-pressure pump input energy.  The desalinated water purity is a function of the feed water salinity, membrane selection and recovery ratio. To achieve higher purity a second pass can be added which generally requires re-pumping. Purity expressed as total dissolved solids typically varies from 100 to 400 parts per million (ppm or mg/litre)on a seawater feed. A level of 500 ppm is generally accepted as the upper limit for drinking water, while the US Food and Drug Administration classifies mineral water as water containing at least 250 ppm.

Energy recovery.

Energy recovery can reduce energy consumption by 50% or more. Much of the high pressure pump input energy can be recovered from the concentrate flow, and the increasing efficiency of energy recovery devices has greatly reduced the energy needs of reverse osmosis desalination. Devices used, in order of invention, are:

Remineralisation and pH adjustment.

The desalinated water is stabilized to protect downstream pipelines and storage, usually by adding lime or caustic soda to prevent corrosion of concrete-lined surfaces. Liming material is used to adjust pH between 6.8 and 8.1 to meet the potable water specifications, primarily for effective disinfection and for corrosion control. Remineralisation may be needed to replace minerals removed from the water by desalination. Although this process has proved to be costly and not very convenient if it is intended to meet mineral demand by humans and plants. The very same mineral demand that freshwater sources provided previously. For instance water from Israel's national water carrier typically contains dissolved magnesium levels of 20 to 25 mg/liter, while water from the Ashkelon plant has no magnesium. After farmers used this water, magnesium-deficiency symptoms appeared in crops, including tomatoes, basil, and flowers, and had to be remedied by fertilization. Current Israeli drinking water standards set a minimum calcium level of 20 mg/liter. The postdesalination treatment in the Ashkelon plant uses sulfuric acid to dissolve calcite (limestone), resulting in calcium concentration of 40 to 46 mg/liter. This is still lower than the 45 to 60 mg/liter found in typical Israeli fresh water.

Disinfection.

Post-treatment consists of preparing the water for distribution after filtration. Reverse osmosis is an effective barrier to pathogens, but post-treatment provides secondary protection against compromised membranes and downstream problems. Disinfection by means of ultraviolet (UV) lamps (sometimes called germicidal or bactericidal) may be employed to sterilize pathogens which bypassed the reverse-osmosis process. Chlorination or chloramination (chlorine and ammonia) protects against pathogens which may have lodged in the distribution system downstream, such as from new construction, backwash, compromised pipes, etc.

Disadvantages.

Household reverse-osmosis units use a lot of water because they have low back pressure. As a result, they recover only 5 to 15% of the water entering the system. The remainder is discharged as waste water. Because waste water carries with it the rejected contaminants, methods to recover this water are not practical for household systems. Wastewater is typically connected to the house drains and will add to the load on the household septic system. A reverse-osmosis unit delivering 19 L of treated water per day may discharge between 75–340 L of waste water daily. This has a disastrous consequence for mega cities like Delhi where large-scale use of household R.O. devices has increased the total water demand of the already water parched National Capital Territory of India.  Large-scale industrial/municipal systems recover typically 75% to 80% of the feed water, or as high as 90%, because they can generate the high pressure needed for higher recovery reverse osmosis filtration. On the other hand, as recovery of wastewater increases in commercial operations, effective contaminant removal rates tend to become reduced, as evidenced by product water total dissolved solids levels.  Reverse osmosis per its construction removes both harmful contaminants present in the water, as well as some desirable minerals. Modern studies on this matter have been quite shallow, citing lack of funding and interest in such study, as re-mineralization on the treatment plants today is done to prevent pipeline corrosion without going into human health aspect. They do, however link to older, more thorough studies that at one hand show some relation between long-term health effects and consumption of water low on calcium and magnesium, on the other confess that none of these older studies comply to modern standards of research

Waste-stream considerations.

Depending upon the desired product, either the solvent or solute stream of reverse osmosis will be waste. For food concentration applications, the concentrated solute stream is the product and the solvent stream is waste. For water treatment applications, the solvent stream is purified water and the solute stream is concentrated waste. The solvent waste stream from food processing may be used as reclaimed water, but there may be fewer options for disposal of a concentrated waste solute stream. Ships may use marine dumping and coastal desalination plants typically use marine outfalls. Landlocked reverse osmosis plants may require evaporation ponds or injection wells to avoid polluting groundwater or surface runoff.

New developments.

Since the 1970s, prefiltration of high-fouling waters with another larger-pore membrane, with less hydraulic energy requirement, has been evaluated and sometimes used. However, this means that the water passes through two membranes and is often repressurized, which requires more energy to be put into the system, and thus increases the cost.  Other recent developmental work has focused on integrating reverse osmosis with electrodialysis to improve recovery of valuable deionized products, or to minimize the volume of concentrate requiring discharge or disposal.  In the production of drinking water, the latest developments include nanoscale and graphene membranes.  The world's largest RO desalination plant was built in Sorek, Israel, in 2013. It has an output of 624,000 m a day. It is also the cheapest and will sell water to the authorities for US$0.58/m.

Reverse osmosis (RO) is a water purification process that uses a partially permeable membrane to remove ions, unwanted molecules and larger particles from drinking water. In reverse osmosis, an applied pressure is used to overcome osmotic pressure, a colligative property that is driven by chemical potential differences of the solvent, a thermodynamic parameter. Reverse osmosis can remove many types of dissolved and suspended chemical species as well as biological ones (principally bacteria) from water, and is used in both industrial processes and the production of potable water. The result is that the solute is retained on the pressurized side of the membrane and the pure solvent is allowed to pass to the other side. To be "selective", this membrane should not allow large molecules or ions through the pores (holes), but should allow smaller components of the solution (such as solvent molecules, i.e., water, HO) to pass freely.

Reverzní osmóza je proces, který dovoluje transport rozpouštědla membránou, zatímco rozpuštěné soli a nízkomolekulární složky zachycuje. Proces je založen na aplikaci vnějšího tlaku ze strany koncentrovanějšího roztoku, což způsobí obrácení přirozeného jevu osmózy.