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Assay

An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity of a target entity. The measured entity is often called the analyte, the measurand, or the target of the assay. The analyte can be a drug, biochemical substance, chemical element or compound, or cell in an organism or organic sample. An assay usually aims to measure an analyte's intensive property and express it in the relevant measurement unit (e.g. molarity, density, functional activity in enzyme international units, degree of effect in comparison to a standard, etc.).

If the assay involves exogenous reactants (the reagents), then their quantities are kept fixed (or in excess) so that the quantity and quality of the target are the only limiting factors. The difference in the assay outcome is used to deduce the unknown quality or quantity of the target in question. Some assays (e.g., biochemical assays) may be similar to chemical analysis and titration. However, assays typically involve biological material or phenomena that are intrinsically more complex in composition or behavior, or both. Thus, reading of an assay may be noisy and involve greater difficulties in interpretation than an accurate chemical titration. On the other hand, older generation qualitative assays, especially bioassays, may be much more gross and less quantitative (e.g., counting death or dysfunction of an organism or cells in a population, or some descriptive change in some body part of a group of animals).

Assays have become a routine part of modern medical, environmental, pharmaceutical, and forensic technology. Other businesses may also employ them at the industrial, curbside, or field levels. Assays in high commercial demand have been well investigated in research and development sectors of professional industries. They have also undergone generations of development and sophistication. In some cases, they are protected by intellectual property regulations such as patents granted for inventions. Such industrial-scale assays are often performed in well-equipped laboratories and with automated organization of the procedure, from ordering an assay to pre-analytic sample processing (sample collection, necessary manipulations e.g. spinning for separation, aliquoting if necessary, storage, retrieval, pipetting, aspiration, etc.). Analytes are generally tested in high-throughput autoanalyzers, and the results are verified and automatically returned to ordering service providers and end-users. These are made possible through the use of an advanced laboratory informatics system that interfaces with multiple computer terminals with end-users, central servers, the physical autoanalyzer instruments, and other automata.

Etymology
According to Etymology Online, the verb assay means "to try, endeavor, strive, test the quality of"; from Anglo-French assaier, from assai (noun), from Old French essai, "trial". Thus the noun assay means "trial, test of quality, test of character" (from mid-14th century), from Anglo-French assai; and its meaning "analysis" is from the late 14th century.

For assay of currency coins this literally meant analysis of the purity of the gold or silver (or whatever the precious component) that represented the true value of the coin. This might have translated later (possibly after the 14th century) into a broader usage of "analysis", e.g., in pharmacology, analysis for an important component of a target inside a mixture—such as the active ingredient of a drug inside the inert excipients in a formulation that previously was measured only grossly by its observable action on an organism (e.g., a lethal dose or inhibitory dose).

General steps
An assay (analysis) is never an isolated process, as it must be accompanied with pre- and post-analytic procedures. Both the communication order (the request to perform an assay plus related information) and the handling of the specimen itself (the collecting, documenting, transporting, and processing done before beginning the assay) are pre-analytic steps. Similarly, after the assay is completed the results must be documented, verified and communicated—the post-analytic steps. As with any multi-step information handling and transmission system, the variation and errors in reporting final results entail not only those intrinsic to the assay itself but also those occurring in the pre-analytic and post-analytic procedures.

While the analytic steps of the assay itself get much attention, it is those that get less attention of the chain of users—the pre-analytic and post-analytic procedures—that typically accumulate the most errors; e.g., pre-analytic steps in medical laboratory assays may contribute 32–75% of all lab errors.

Assays can be very diverse, but generally involve the following general steps:
 * 1) Sample processing and manipulation in order to selectively present the target in a discernible or measurable form to a discrimination/identification/detection system. It might involve a simple centrifugal separation or washing or filtration or capture by some form of selective binding or it may even involve modifying the target e.g. epitope retrieval in immunological assays or cutting down the target into pieces e.g. in Mass Spectrometry. Generally there are multiple separate steps done before an assay and are called preanalytic processing. But some of the manipulations may be inseparable part of the assay itself and will not thus be considered pre-analytic.
 * 2) Target-specific discrimination/identification principle: to discriminate from background (noise) of similar components and specifically identify a particular target component ("analyte") in a biological material by its specific attributes. (e.g. in a PCR assay a specific oligonucleotide primer identifies the target by base pairing based on the specific nucleotide sequence unique to the target).
 * 3) Signal (or target) amplification system: The presence and quantity of that analyte is converted into a detectable signal generally involving some method of signal amplification, so that it can be easily discriminated from noise and measured - e.g. in a PCR assay among a mixture of DNA sequences only the specific target is amplified into millions of copies by a DNA polymerase enzyme so that it can be discerned as a more prominent component compared to any other potential components. Sometimes the concentration of the analyte is too large and in that case the assay may involve sample dilution or some sort of signal diminution system which is a negative amplification.
 * 4) Signal detection (and interpretation) system: A system of deciphering the amplified signal into an interpretable output that can be quantitative or qualitative. It can be visual or manual very crude methods or can be very sophisticated electronic digital or analog detectors.
 * 5) Signal enhancement and noise filtering may be done at any or all of the steps above. Since the more downstream a step/process during an assay, the higher the chance of carrying over noise from the previous process and amplifying it, multiple steps in a sophisticated assay might involve various means of signal-specific sharpening/enhancement arrangements and noise reduction or filtering arrangements. These may simply be in the form of a narrow band-pass optical filter, or a blocking reagent in a binding reaction that prevents nonspecific binding or a quenching reagent in a fluorescence detection system that prevents "autofluorescence" of background objects.

Time and number of measurements taken
Depending on whether an assay just looks at a single time point or timed readings taken at multiple time points, an assay may be:
 * 1) An end point assay, in which a single measurement is performed after a fixed incubation period; or
 * 2) A kinetic assay, in which measurements are performed multiple times over a fixed time interval. Kinetic assay results may be visualized numerically (for example, as a slope parameter representing the rate of signal change over time), or graphically (for example, as a plot of the signal measured at each time point). For kinetic assays, both the magnitude and shape of the measured response over time provide important information.
 * 3) A high throughput assay can be either an endpoint or a kinetic assay usually done on an automated platform in 96-, 384- or 1536-well microplate formats (High Throughput Screening). Such assays are able to test large number of compounds or analytes or make functional biological readouts in response to a stimuli and/or compounds being tested.

Number of analytes detected
Depending on how many targets or analytes are being measured:
 * 1) Usual assays are simple or single target assays which is usually the default unless it is called multiplex.
 * 2) Multiplex assays are used to simultaneously measure the presence, concentration, activity, or quality of multiple analytes in a single test. The advent of multiplexing enabled rapid, efficient sample testing in many fields, including immunology, cytochemistry, genetics/genomics, pharmacokinetics, and toxicology.

Result type
Depending on the quality of the result produced, assays may be classified into:
 * 1) Qualitative assays, i.e. assays which generally give just a pass or fail, or positive or negative or some such sort of only small number of qualitative gradation rather than an exact quantity.
 * 2) Semi-quantitative assays, i.e. assays that give the read-out in an approximate fashion rather than an exact number for the quantity of the substance. Generally they have a few more gradations than just two outcomes, positive or negative, e.g. scoring on a scale of 1+ to 4+ as used for blood grouping tests based on RBC agglutination in response to grouping reagents (antibody against blood group antigens).
 * 3) Quantitative assays, i.e. assays that give accurate and exact numeric quantitative measure of the amount of a substance in a sample. An example of such an assay used in coagulation testing laboratories for the most common inherited bleeding disease - Von Willebrand disease is VWF antigen assay where the amount of VWF present in a blood sample is measured by an immunoassay.
 * 4) Functional assays, i.e. an assay that tries to quantify functioning of an active substance rather than just its quantity. The functional counterpart of the VWF antigen assay is Ristocetin Cofactor assay, which measures the functional activity of the VWF present in a patient's plasma by adding exogenous formalin-fixed platelets and gradually increasing quantities of drug named ristocetin while measuring agglutination of the fixed platelets. A similar assay but used for a different purpose is called Ristocetin Induced Platelet Aggregation or RIPA, which tests response of endogenous live platelets from a patient in response to Ristocetin (exogenous) & VWF (usually endogenous).

Sample type and method
Depending on the general substrate on which the assay principle is applied:
 * 1) Bioassay: when the response is biological activity of live objects. Examples include
 * 2) in vivo, whole organism (e.g. mouse or other subject injected with a drug)
 * 3) ex vivo body part (e.g. leg of a frog)
 * 4) ex vivo organ (e.g. heart of a dog)
 * 5) ex vivo part of an organ (e.g. a segment of an intestine).
 * 6) tissue (e.g. limulus lysate)
 * 7) cell (e.g. platelets)
 * 8) Ligand binding assay when a ligand (usually a small molecule) binds a receptor (usually a large protein).
 * 9) Immunoassay when the response is an antigen antibody binding type reaction.

Signal amplification
Depending on the nature of the signal amplification system assays may be of numerous types, to name a few:
 * 1) Enzyme assay: Enzymes may be tested by their highly repeating activity on a large number of substrates when loss of a substrate or the making of a product may have a measurable attribute like color or absorbance at a particular wavelength or light or Electrochemiluminescence or electrical/redox activity.
 * 2) Light detection systems that may use amplification e.g. by a photodiode or a photomultiplier tube or a cooled charge coupled device.
 * 3) Radioisotope labeled substrates as used in radioimmunoassays and equilibrium dialysis assays and can be detected by the amplification in Gamma counters or X-ray plates, or phosphorimager
 * 4) Polymerase Chain Reaction Assays that amplify a DNA (or RNA) target rather than the signal
 * 5) Combination Methods Assays may utilize a combination of the above and other amplification methods to improve sensitivity. e.g. Enzyme-linked immunoassay or EIA, enzyme linked immunosorbent assay.

Detection method or technology
Depending on the nature of the Detection system assays can be based on:
 * 1) Colony forming or virtual colony count: e.g. by multiplying bacteria or proliferating cells.
 * 2) Photometry / spectrophotometry When the absorbance of a specific wavelength of light while passing through a fixed path-length through a cuvette of liquid test sample is measured and the absorbance is compared with a blank and standards with graded amounts of the target compound. If the emitted light is of a specific visible wavelength it may be called colorimetry, or it may involve specific wavelength of light e.g. by use of laser and emission of fluorescent signals of another specific wavelength which is detected via very specific wavelength optical filters.
 * 3) Transmittance of light may be used to measure e.g. clearing of opacity of a liquid created by suspended particles due to decrease in number of clumps during a platelet agglutination reaction.
 * 4) Turbidimetry when the opacity of straight-transmitted light passing through a liquid sample is measured by detectors placed straight across the light source.
 * 5) Nephelometry where a measurement of the amount of light scattering that occurs when a beam of light is passed through the solution is used to determine size and/or concentration and/or size distribution of particles in the sample.
 * 6) Reflectometry When color of light reflected from a (usually dry) sample or reactant is assessed e.g. the automated readings of the strip urine dipstick assays.
 * 7) Viscoelastic measurements e.g. viscometry, elastography (e.g. thromboelastography)
 * 8) Counting assays: e.g. optic Flow cytometric cell or particle counters, or coulter/impedance principle based cell counters
 * 9) Imaging assays, that involve image analysis manually or by software:
 * 10) Cytometry: When the size statistics of cells is assessed by an image processor.
 * 11) Electric detection e.g. involving amperometry, Voltammetry, coulometry may be used directly or indirectly for many types of quantitative measurements.
 * 12) Other physical property based assays may use
 * 13) Osmometer
 * 14) Viscometer
 * 15) Ion Selective electrodes
 * 16) Syndromic testing

DNA
Assays for studying interactions of proteins with DNA include:
 * DNase footprinting assay
 * Filter binding assay
 * Gel shift assay

Protein

 * Bicinchoninic acid assay (BCA assay)
 * Bradford protein assay
 * Lowry protein assay
 * Secretion assay

RNA

 * Nuclear run-on
 * Ribosome profiling

Cell counting, viability, proliferation or cytotoxicity assays
A cell-counting assay may determine the number of living cells, the number of dead cells, or the ratio of one cell type to another, such as enumerating and typing red versus different types of white blood cells. This is measured by different physical methods (light transmission, electric current change). But other methods use biochemical probing cell structure or physiology (stains). Another application is to monitor cell culture (assays of cell proliferation or cytotoxicity). A cytotoxicity assay measures how toxic a chemical compound is to cells.
 * MTT assay
 * Cell Counting Kit-8 (WST-8 based cell viability assay)
 * SRB (Sulforhodamine B) assay
 * CellTiter-Glo® Luminescent Cell Viability Assay
 * Cell counting instruments and methods: CASY cell counting technology, Coulter counter, Electric cell-substrate impedance sensing
 * Cell viability assays: resazurin method, ATP test, Ethidium homodimer assay (detect dead or dying cells), Bacteriological water analysis, Clonogenic assays, ...

Environmental or food contaminants

 * Bisphenol F
 * Aquatic toxicity tests

Surfactants

 * An MBAS assay indicates anionic surfactants in water with a bluing reaction.

Other cell assays
Many cell assays have been developed to assess specific parameters or response of cells (biomarkers, cell physiology). Techniques used to study cells include : Metastasis Assay
 * reporter assays using i.e. Luciferase, calcium signaling assays using Coelenterazine, CFSE or Calcein
 * Immunostaining of cells on slides by Microscopy (ImmunoHistoChemistry or Fluorescence), on microplates by photometry including the ELISpot (and its variant FluoroSpot) to enumerate B-Cells or antigen-specific cells, in solution by Flow cytometry
 * Molecular biology techniques such as DNA microarrays, in situ hybridization, combined to PCR, Computational genomics, and Transfection; Cell fractionation or Immunoprecipitation
 * Migration assays, Chemotaxis assay
 * Secretion assays
 * Apoptosis assays such as the DNA laddering assay, the Nicoletti assay, caspase activity assays, and Annexin V staining
 * Chemosensitivity assay measures the number of tumor cells that are killed by a cancer drug
 * Tetramer assay detect the presence of antigen specific T-cells
 * Gentamicin protection assay or survival assay or invasion assay to assess ability of pathogens (bacteria) to invade eukaryotic cells

Petrochemistry

 * Crude oil assay

Virology
The HPCE-based viral titer assay uses a proprietary, high-performance capillary electrophoresis system to determine baculovirus titer.

The Trofile assay is used to determine HIV tropism.

The viral plaque assay is to calculate the number of viruses present in a sample. In this technique the number of viral plaques formed by a viral inoculum is counted, from which the actual virus concentration can be determined.

Cellular secretions
A wide range of cellular secretions (say, a specific antibody or cytokine) can be detected using the ELISA technique. The number of cells which secrete those particular substances can be determined using a related technique, the ELISPOT assay.

Drugs

 * Testing for Illegal Drugs
 * Radioligand binding assay

Quality
When multiple assays measure the same target their results and utility may or may not be comparable depending on the natures of the assay and their methodology, reliability etc. Such comparisons are possible through study of general quality attributes of the assays e.g. principles of measurement (including identification, amplification and detection), dynamic range of detection (usually the range of linearity of the standard curve), analytic sensitivity, functional sensitivity, analytic specificity, positive, negative predictive values, turn around time i.e. time taken to finish a whole cycle from the preanalytic steps till the end of the last post analytic step (report dispatch/transmission), throughput i.e. number of assays done per unit time (usually expressed as per hour) etc. Organizations or laboratories that perform Assays for professional purposes e.g. medical diagnosis and prognostics, environmental analysis, forensic proceeding, pharmaceutical research and development must undergo well regulated quality assurance procedures including method validation, regular calibration, analytical quality control, proficiency testing, test accreditation, test licensing and must document appropriate certifications from the relevant regulating bodies in order to establish the reliability of their assays, especially to remain legally acceptable and accountable for the quality of the assay results and also to convince customers to use their assay commercially/professionally.

Bioactivity databases
Bioactivity databases correlate structures or other chemical information to bioactivity results taken from bioassays in literature, patents, and screening programs.

Protocol databases
Protocol databases correlate results from bioassays to their metadata about experimental conditions and protocol designs.

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Nuclease

In biochemistry, a nuclease (also archaically known as nucleodepolymerase or polynucleotidase) is an enzyme capable of cleaving the phosphodiester bonds between nucleotides of nucleic acids. Nucleases variously effect single and double stranded breaks in their target molecules. In living organisms, they are essential machinery for many aspects of DNA repair. Defects in certain nucleases can cause genetic instability or immunodeficiency. Nucleases are also extensively used in molecular cloning.

There are two primary classifications based on the locus of activity. Exonucleases digest nucleic acids from the ends. Endonucleases act on regions in the middle of target molecules. They are further subcategorized as deoxyribonucleases and ribonucleases. The former acts on DNA, the latter on RNA.

History
In the late 1960s, scientists Stuart Linn and Werner Arber isolated examples of the two types of enzymes responsible for phage growth restriction in Escherichia coli (E. coli) bacteria. One of these enzymes added a methyl group to the DNA, generating methylated DNA, while the other cleaved unmethylated DNA at a wide variety of locations along the length of the molecule. The first type of enzyme was called a "methylase" and the other a "restriction nuclease". These enzymatic tools were important to scientists who were gathering the tools needed to "cut and paste" DNA molecules. What was then needed was a tool that would cut DNA at specific sites, rather than at random sites along the length of the molecule, so that scientists could cut DNA molecules in a predictable and reproducible way.

An important development came when H.O. Smith, K.W. Wilcox, and T.J. Kelly, working at Johns Hopkins University in 1968, isolated and characterized the first restriction nuclease whose functioning depended on a specific DNA nucleotide sequence. Working with Haemophilus influenzae bacteria, this group isolated an enzyme, called HindII, that always cut DNA molecules at a particular point within a specific sequence of six base pairs. They found that the HindII enzyme always cuts directly in the center of this sequence (between the 3rd and 4th base pairs).

Numerical Classification System
Most nucleases are classified by the Enzyme Commission number of the "Nomenclature Committee of the International Union of Biochemistry and Molecular Biology" as hydrolases (EC-number 3). The nucleases belong just like phosphodiesterase, lipase and phosphatase to the esterases (EC-number 3.1), a subgroup of the hydrolases. The esterases to which nucleases belong are classified with the EC-numbers 3.1.11 - EC-number 3.1.31.

Structure
Nuclease primary structure is by and large poorly conserved and minimally conserved at active sites, the surfaces of which primarily comprise acidic and basic amino acid residues. Nucleases can be classified into folding families.

Site recognition
A nuclease must associate with a nucleic acid before it can cleave the molecule. That entails a degree of recognition. Nucleases variously employ both nonspecific and specific associations in their modes of recognition and binding. Both modes play important roles in living organisms, especially in DNA repair.

Nonspecific endonucleases involved in DNA repair can scan DNA for target sequences or damage. Such a nuclease diffuses along DNA until it encounters a target, upon which the residues of its active site interact with the chemical groups of the DNA. In the case of endonucleases such as EcoRV, BamHI, and PvuII, this nonspecific binding involves electrostatic interactions between minimal surface area of the protein and the DNA. This weak association leaves the overall shape of the DNA undeformed, remaining in B-form.

A forms far stronger associations by contrast. It draws DNA into the deep groove of its DNA-binding domain. This results in significant deformation of the DNA tertiary structure and is accomplished with a surfaces rich in basic (positively charged) residues. It engages in extensive electrostatic interaction with the DNA.

Some nucleases involved in DNA repair exhibit partial sequence-specificity. However most are nonspecific, instead recognizing structural abnormalities produced in the DNA backbone by base pair mismatches.

Structure specific nuclease
For details see flap endonuclease.

Sequence specific nuclease
There are more than 900 restriction enzymes, some sequence specific and some not, have been isolated from over 230 strains of bacteria since the initial discovery of HindII. These restriction enzymes generally have names that reflect their origin—The first letter of the name comes from the genus and the second two letters come from the species of the prokaryotic cell from which they were isolated. For example, EcoRI comes from Escherichia coli RY13 bacteria, while HindII comes from Haemophilus influenzae strain Rd. Numbers following the nuclease names indicate the order in which the enzymes were isolated from single strains of bacteria: EcoRI, EcoRII.

Endonucleases
A restriction endonuclease functions by "scanning" the length of a DNA molecule. Once it encounters its particular specific recognition sequence, it will bind to the DNA molecule and makes one cut in each of the two sugar-phosphate backbones. The positions of these two cuts, both in relation to each other, and to the recognition sequence itself, are determined by the identity of the restriction endonuclease. Different endonucleases yield different sets of cuts, but one endonuclease will always cut a particular base sequence the same way, no matter what DNA molecule it is acting on. Once the cuts have been made, the DNA molecule will break into fragments.

Staggered cutting
Not all restriction endonucleases cut symmetrically and leave blunt ends like HindII described above. Many endonucleases cleave the DNA backbones in positions that are not directly opposite each other, creating overhangs. For example, the nuclease EcoRI has the recognition sequence.

When the enzyme encounters this sequence, it cleaves each backbone between the G and the closest A base residues. Once the cuts have been made, the resulting fragments are held together only by the relatively weak hydrogen bonds that hold the complementary bases to each other. The weakness of these bonds allows the DNA fragments to separate from each other. Each resulting fragment has a protruding 5' end composed of unpaired bases. Other enzymes create cuts in the DNA backbone which result in protruding 3' ends. Protruding ends—both 3' and 5'—are sometimes called "sticky ends" because they tend to bond with complementary sequences of bases. In other words, if an unpaired length of bases  encounters another unpaired length with the sequence   they will bond to each other—they are "sticky" for each other. Ligase enzyme is then used to join the phosphate backbones of the two molecules. The cellular origin, or even the species origin, of the sticky ends does not affect their stickiness. Any pair of complementary sequences will tend to bond, even if one of the sequences comes from a length of human DNA, and the other comes from a length of bacterial DNA. In fact, it is this quality of stickiness that allows production of recombinant DNA molecules, molecules which are composed of DNA from different sources, and which has given birth to the genetic engineering technology.

DNA repair
With all cells depending on DNA as the medium of genetic information, genetic quality control is an essential function of all organisms. DNA replication is an error prone process, and DNA molecules themselves are vulnerable to modification by many metabolic and environmental stressors. Ubiquitous examples include reactive oxygen species, near ultraviolet, and ionizing radiation. Many nucleases participate in DNA repair by recognizing damage sites and cleaving them from the surrounding DNA. These enzymes function independently or in complexes. Most nucleases involved in DNA repair are not sequence-specific. They recognize damage sites through deformation of double stranded DNA (dsDNA) secondary structure.

Replication proofreading
During DNA replication, DNA polymerases elongate new strands of DNA against complementary template strands. Most DNA polymerases comprise two different enzymatic domains: a polymerase and a proofreading exonuclease. The polymerase elongates the new strand in the 5' → 3' direction. The exonuclease removes erroneous nucleotides from the same strand in the 3’ → 5’ direction. This exonuclease activity is essential for a DNA polymerase's ability to proofread. Deletions inactivating or removing these nucleases increase rates of mutation and mortality in affected microbes and cancer in mice.

Halted replication fork
Many forms of DNA damage stop progression of the replication fork, causing the DNA polymerases and associated machinery to abandon the fork. It must then be processed by fork-specific proteins. The most notable is MUS81. Deletions of which causes UV or methylation damage sensitivity in yeast, in addition to meiotic defects.

Okazaki fragment processing
A ubiquitous task in cells is the removal of Okazaki fragment RNA primers from replication. Most such primers are excised from newly synthesized lagging strand DNA by endonucleases of the family RNase H. In eukaryotes and in archaea, the flap endonuclease FEN1 also participates in the processing of Okazaki fragments.

Mismatch repair
DNA mismatch repair in any given organism is effected by a suite of mismatch-specific endonucleases. In prokaryotes, this role is primarily filled by MutSLH and very short patch repair (VSP repair) associated proteins.

The MutSLH system (comprising MutS, MutL, and MutH) corrects point mutations and small turns. MutS recognizes and binds to mismatches, where it recruits MutL and MutH. MutL mediates the interaction between MutS and MutH, and enhances the endonucleasic activity of the latter. MutH recognizes hemimethylated  sites and cleaves next to the   of the non-methylated strand (the more recently synthesized strand).

VSP repair is initiated by the endonuclease Vsr. It corrects a specific  mismatch caused by the spontaneous deamination of methylated cytosines to thymines. Vsr recognizes the sequence , where it nicks the DNA strand on the 5' side of the mismatched thymine (underlined in the previous sequence). One of the exonucleases RecJ, ExoVII, or ExoI then degrades the site before DNA polymerase resynthesizes the gap in the strand.

Base excision repair
AP site formation is a common occurrence in dsDNA. It is the result of spontaneous hydrolysis and the activity of DNA glycosylases as an intermediary step in base excision repair. These AP sites are removed by AP endonucleases, which effect single strand breaks around the site.

Nucleotide excision repair
Nucleotide excision repair, not to be confused with base excision repair, involves the removal and replacement of damaged nucleotides. Instances of crosslinking, adducts, and lesions (generated by ultraviolet light or reactive oxygen species) can trigger this repair pathway. Short stretches of single stranded DNA containing such damaged nucleotide are removed from duplex DNA by separate endonucleases effecting nicks upstream and downstream of the damage. Deletions or mutations which affect these nucleases instigate increased sensitivity to ultraviolet damage and carcinogenesis. Such abnormalities can even impinge neural development.

In bacteria, both cuts executed by the UvrB-UvrC complex. In budding yeast, Rad2 and the Rad1-Rad10 complex make the 5' and 3' cuts, respectively. In mammals, the homologs XPG and XPF-ERCC1 affect the same respective nicks.

Double-strand break repair
Double-strand breaks, both intentional and unintentional, regularly occur in cells. Unintentional breaks are commonly generated by ionizing radiation, various exogenous and endogenous chemical agents, and halted replication forks. Intentional breaks are generated as intermediaries in meiosis and V(D)J recombination, which are primarily repaired through homologous recombination and non-homologous end joining. Both cases require the ends in double strand breaks be processed by nucleases before repair can take place. One such nuclease is Mre11 complexed with Rad50. Mutations of Mre11 can precipitate ataxia-telangiectasia-like disorder.

V(D)J recombination involves opening stem-loops structures associated with double-strand breaks and subsequently joining both ends. The Artemis-DNAPKcs complex participates in this reaction. Although Artemis exhibits 5' → 3' ssDNA exonuclease activity when alone, its complexing with DNA-PKcs allows for endonucleasic processing of the stem-loops. Defects of either protein confers severe immunodeficiency.

Homologous recombination, on the other hand, involves two homologous DNA duplexes connected by D-loops or Holliday junctions. In bacteria, endonucleases like RuvC resolve Holliday junctions into two separate dsDNAs by cleaving the junctions at two symmetrical sites near the junction centre. In eukaryotes, FEN1, XPF-ERCC1, and MUS81 cleave the D-loops, and Cce1/Ydc2 processes Holliday junctions in mitochondria.

Meganucleases
The frequency at which a particular nuclease will cut a given DNA molecule depends on the complexity of the DNA and the length of the nuclease's recognition sequence; due to the statistical likelihood of finding the bases in a particular order by chance, a longer recognition sequence will result in less frequent digestion. For example, a given four-base sequence (corresponding to the recognition site for a hypothetical nuclease) would be predicted to occur every 256 base pairs on average (where 4^4=256), but any given six-base sequence would be expected to occur once every 4,096 base pairs on average (4^6=4096).

One unique family of nucleases is the meganucleases, which are characterized by having larger, and therefore less common, recognition sequences consisting of 12 to 40 base pairs. These nucleases are particularly useful for genetic engineering and Genome engineering applications in complex organisms such as plants and mammals, where typically larger genomes (numbering in the billions of base pairs) would result in frequent and deleterious site-specific digestion using traditional nucleases.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Nuclease


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User talk:Pcalcado

Welcome. Are you William Sawyer? Do you have permission to upload the images which appear to be created by him and from his web site? Jamesday 01:30, 1 Mar 2004 (UTC)

title: User talk:Pcalcado


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Operator topologies

In the mathematical field of functional analysis there are several standard topologies which are given to the algebra $B(X)$ of bounded linear operators on a Banach space $X$.

Introduction
Let $$(T_n)_{n \in \mathbb N}$$ be a sequence of linear operators on the Banach space $X$. Consider the statement that $$(T_n)_{n \in \N}$$ converges to some operator $T$ on $X$. This could have several different meanings:
 * If $$\|T_n - T\| \to 0$$, that is, the operator norm of $$T_n - T$$ (the supremum of $$\| T_n x - T x \|_X$$, where $x$ ranges over the unit ball in $X$ ) converges to 0, we say that $$T_n \to T$$ in the uniform operator topology.
 * If $$T_n x \to Tx$$ for all $$x \in X$$, then we say $$T_n \to T$$ in the strong operator topology.
 * Finally, suppose that for all $x ∈ X$ we have $$T_n x \to Tx$$ in the weak topology of $X$. This means that $$F(T_n x) \to F(T x)$$ for all continuous linear functionals $F$ on $X$. In this case we say that $$T_n \to T$$ in the weak operator topology.

List of topologies on B(H)

There are many topologies that can be defined on $B(X)$ besides the ones used above; most are at first only defined when $B(X)$ is a Hilbert space, even though in many cases there are appropriate generalisations. The topologies listed below are all locally convex, which implies that they are defined by a family of seminorms.

In analysis, a topology is called strong if it has many open sets and weak if it has few open sets, so that the corresponding modes of convergence are, respectively, strong and weak. (In topology proper, these terms can suggest the opposite meaning, so strong and weak are replaced with, respectively, fine and coarse.) The diagram on the right is a summary of the relations, with the arrows pointing from strong to weak.

If $H$ is a Hilbert space, the linear space of Hilbert space operators $X = H$ has a (unique) predual $$B(H)_*$$, consisting of the trace class operators, whose dual is $B(X)$. The seminorm $B(X)$ for w positive in the predual is defined to be $p_{w}(x)$.

If $B$ is a vector space of linear maps on the vector space $A$, then $B(w, x^{*}x)^{1/2}$ is defined to be the weakest topology on $A$ such that all elements of $B$ are continuous.

 * The norm topology or uniform topology or uniform operator topology is defined by the usual norm ||x|| on $σ(A, B)$. It is stronger than all the other topologies below.
 * The weak (Banach space) topology is $B(H)$, in other words the weakest topology such that all elements of the dual $σ(B(H), B(H)^{*})$ are continuous. It is the weak topology on the Banach space $B(H)^{*}$. It is stronger than the ultraweak and weak operator topologies. (Warning: the weak Banach space topology and the weak operator topology and the ultraweak topology are all sometimes called the weak topology, but they are different.)
 * The Mackey topology or Arens-Mackey topology is the strongest locally convex topology on $B(H)$ such that the dual is $B(H)$, and is also the uniform convergence topology on $B(H)_{*}$, $Bσ(B(H)_{*}$-compact convex subsets of $B(H)$. It is stronger than all topologies below.
 * The σ-strong-* topology or ultrastrong-* topology is the weakest topology stronger than the ultrastrong topology such that the adjoint map is continuous. It is defined by the family of seminorms $B(H)_{*}$ and $p_{w}(x)$ for positive elements $w$ of $p_{w}(x^{*})$. It is stronger than all topologies below.
 * The σ-strong topology or ultrastrong topology or strongest topology or strongest operator topology is defined by the family of seminorms $B(H)_{*}$ for positive elements $w$ of $p_{w}(x)$. It is stronger than all the topologies below other than the strong* topology. Warning: in spite of the name "strongest topology", it is weaker than the norm topology.)
 * The σ-weak topology or ultraweak topology or weak-* operator topology or weak-* topology or weak topology or $B(H)_{*}$) topology is defined by the family of seminorms |(w, x)| for elements w of $σ(B(H), B(H)_{*}$. It is stronger than the weak operator topology. (Warning: the weak Banach space topology and the weak operator topology and the ultraweak topology are all sometimes called the weak topology, but they are different.)
 * The strong-* operator topology or strong-* topology is defined by the seminorms ||x(h)|| and ||x*(h)|| for $B(H)_{*}$. It is stronger than the strong and weak operator topologies.
 * The strong operator topology (SOT) or strong topology is defined by the seminorms ||x(h)|| for $h ∈ H$. It is stronger than the weak operator topology.
 * The weak operator topology (WOT) or weak topology is defined by the seminorms |(x(h1), h2)| for $h ∈ H$. (Warning: the weak Banach space topology, the weak operator topology, and the ultraweak topology are all sometimes called the weak topology, but they are different.)

Relations between the topologies
The continuous linear functionals on $h_{1}, h_{2} ∈ H$ for the weak, strong, and strong* (operator) topologies are the same, and are the finite linear combinations of the linear functionals (xh1, h2) for $B(H)$. The continuous linear functionals on $h_{1}, h_{2} ∈ H$ for the ultraweak, ultrastrong, ultrastrong* and Arens-Mackey topologies are the same, and are the elements of the predual $B(H)$.

By definition, the continuous linear functionals in the norm topology are the same as those in the weak Banach space topology. This dual is a rather large space with many pathological elements.

On norm bounded sets of $B(H)_{*}$, the weak (operator) and ultraweak topologies coincide. This can be seen via, for instance, the Banach–Alaoglu theorem. For essentially the same reason, the ultrastrong topology is the same as the strong topology on any (norm) bounded subset of $B(H)$. Same is true for the Arens-Mackey topology, the ultrastrong*, and the strong* topology.

In locally convex spaces, closure of convex sets can be characterized by the continuous linear functionals. Therefore, for a convex subset $K$ of $B(H)$, the conditions that $K$ be closed in the ultrastrong*, ultrastrong, and ultraweak topologies are all equivalent and are also equivalent to the conditions that for all $B(H)$, $K$ has closed intersection with the closed ball of radius $r$ in the strong*, strong, or weak (operator) topologies.

The norm topology is metrizable and the others are not; in fact they fail to be first-countable. However, when $H$ is separable, all the topologies above are metrizable when restricted to the unit ball (or to any norm-bounded subset).

Topology to use
The most commonly used topologies are the norm, strong, and weak operator topologies. The weak operator topology is useful for compactness arguments, because the unit ball is compact by the Banach–Alaoglu theorem. The norm topology is fundamental because it makes $r > 0$ into a Banach space, but it is too strong for many purposes; for example, $B(H)$ is not separable in this topology. The strong operator topology could be the most commonly used.

The ultraweak and ultrastrong topologies are better-behaved than the weak and strong operator topologies, but their definitions are more complicated, so they are usually not used unless their better properties are really needed. For example, the dual space of $B(H)$ in the weak or strong operator topology is too small to have much analytic content.

The adjoint map is not continuous in the strong operator and ultrastrong topologies, while the strong* and ultrastrong* topologies are modifications so that the adjoint becomes continuous. They are not used very often.

The Arens–Mackey topology and the weak Banach space topology are relatively rarely used.

To summarize, the three essential topologies on $B(H)$ are the norm, ultrastrong, and ultraweak topologies. The weak and strong operator topologies are widely used as convenient approximations to the ultraweak and ultrastrong topologies. The other topologies are relatively obscure.

title: Operator topologies


text:
Argentine (disambiguation)

Argentine is a citizen of Argentina.

Argentine, Argentinian and Argentinean may also refer to:

Places

 * Argentine, Kansas, United States
 * Argentine, Michigan, United States
 * Argentine, Savoie, a commune in France
 * Argentine Township, Michigan, United States
 * Argentine Township, Fall River County, South Dakota, United States
 * Argentine (Paris Métro)
 * L'Argentine, a mountain in the Alps

Other uses

 * Silver and other similar metals
 * Argentine (fish), a fish in the family Argentinidae or the herring smelts
 * Spatalia argentina or Argentine, a moth in the family Notodontidae
 * The Argentine, the subtitle for part one of the 2008 biopic Che about Che Guevara starring Benicio del Toro

title: Argentine (disambiguation)


text:
User:Fibonacci

es:Usuario:Fibonacci

Bonjourno, my neme ists Georgie. English is not my mother tongue, so there may (will) be grammar and/or spelling mistakes on this page. However, I think my English is good enough so as to get my point across.

I'm from Milan, but I've been living in Bogotá (Colombia) for a long time. I'm a physicist and mathematician from the Universidad de Los Andes (that's the reason for my nickname), and am currently working on my master's degree.

I found out about Wikipedia some time ago, thanks to a search on Google about furry (yes, I'm a furry, a red fox, if you want to know), and now I search it for almost anything, everyday. I think it's great and everybody should know about it (thanks, Jimbo!).

Contributions? There is a link at the bottom of this page, but if you're as lazy as I am (i.e. too lazy to go to the bottom), click here. Or here, to see the files I've uploaded.

Wanna send me a message? go to this page.

Other Wikimedia sites I contribute to
... though I spend most of my (not so) free time here, even more than on es:.
 * Meta-Wiki (my user page)
 * Wikimedia Commons (my user page)
 * Wikiquote (my user page)
 * Wiktionary (my user page)

My sandbox, I don't know why did I put this link here since probably it will be useful only to me. Anyway...

title: User:Fibonacci


text:
Sigma factor

A sigma factor (σ factor or specificity factor) is a protein needed for initiation of transcription in bacteria. It is a bacterial transcription initiation factor that enables specific binding of RNA polymerase (RNAP) to gene promoters. It is homologous to archaeal transcription factor B and to eukaryotic factor TFIIB. The specific sigma factor used to initiate transcription of a given gene will vary, depending on the gene and on the environmental signals needed to initiate transcription of that gene. Selection of promoters by RNA polymerase is dependent on the sigma factor that associates with it. They are also found in plant chloroplasts as a part of the bacteria-like plastid-encoded polymerase (PEP).

The sigma factor, together with RNA polymerase, is known as the RNA polymerase holoenzyme. Every molecule of RNA polymerase holoenzyme contains exactly one sigma factor subunit, which in the model bacterium Escherichia coli is one of those listed below. The number of sigma factors varies between bacterial species. E. coli has seven sigma factors. Sigma factors are distinguished by their characteristic molecular weights. For example, σ70 is the sigma factor with a molecular weight of 70 kDa.

The sigma factor in the RNA polymerase holoenzyme complex is required for the initiation of transcription, although once that stage is finished, it is dissociated from the complex and the RNAP continues elongation on its own.

Specialized sigma factors
Different sigma factors are utilized under different environmental conditions. These specialized sigma factors bind the promoters of genes appropriate to the environmental conditions, increasing the transcription of those genes.

Sigma factors in E. coli:
 * σ70(RpoD) – σA – the "housekeeping" sigma factor or also called as primary sigma factor (Group 1), transcribes most genes in growing cells. Every cell has a "housekeeping" sigma factor that keeps essential genes and pathways operating. In the case of E. coli and other gram-negative rod-shaped bacteria, the "housekeeping" sigma factor is σ70.  Genes recognized by σ70 all contain similar promoter consensus sequences consisting of two parts.  Relative to the DNA base corresponding to the start of the RNA transcript, the consensus promoter sequences are characteristically centered at 10 and 35 nucleotides before the start of transcription (−10 and −35).
 * σ19 (FecI) – the ferric citrate sigma factor, regulates the fec gene for iron transport and metabolism
 * σ24 (RpoE) – extreme heat stress response and the extracellular proteins sigma factor
 * σ28 (RpoF/FliA) – the flagellar synthesis and chemotaxis sigma factor
 * σ32 (RpoH) – the heat shock sigma factor, it is turned on when the bacteria are exposed to heat. Due to the higher expression, the factor will bind with a high probability to the polymerase-core-enzyme. Doing so, other heatshock proteins are expressed, which enable the cell to survive higher temperatures. Some of the enzymes that are expressed upon activation of σ32 are chaperones, proteases and DNA-repair enzymes.
 * σ38 (RpoS) – the starvation/stationary phase sigma factor
 * σ54 (RpoN) – the nitrogen-limitation sigma factor

There are also anti-sigma factors that inhibit the function of sigma factors and anti-anti-sigma factors that restore sigma factor function.

Structure

By sequence similarity, most sigma factors are σ70-like. They have four main regions (domains) that are generally conserved:

N-terminus - C-terminus 1.1   2    3    4

The regions are further subdivided. For example, region 2 includes 1.2 and 2.1 through 2.4.

Domain 1.1 is found only in "primary sigma factors" (RpoD, RpoS in E.coli; "Group 1"). It is involved in ensuring the sigma factor will only bind the promoter when it is complexed with the RNA polymerase. Domains 2-4 each interact with specific promoter elements and with RNAP. Region 2.4 recognizes and binds to the promoter −10 element (called the "Pribnow box"). Region 4.2 recognizes and binds to the promoter −35 element.

Not every sigma factor of the σ70 family contains all the domains. Group 2, which includes RpoS, is very similar to Group 1 but lacks domain 1. Group 3 also lacks domain 1, and includes σ28. Group 4, also known as the Extracytoplasmic Function (ECF) group, lack both σ1.1 and σ3. RpoE is a member.

Other known sigma factors are of the σ54/RpoN type. They are functional sigma factors, but they have significantly different primary amino acid sequences.

Retention during transcription elongation
The core RNA polymerase (consisting of 2 alpha (α), 1 beta (β), 1 beta-prime (β'), and 1 omega (ω) subunits) binds a sigma factor to form a complex called the RNA polymerase holoenzyme. It was previously believed that the RNA polymerase holoenzyme initiates transcription, while the core RNA polymerase alone synthesizes RNA. Thus, the accepted view was that sigma factor must dissociate upon transition from transcription initiation to transcription elongation (this transition is called "promoter escape"). This view was based on analysis of purified complexes of RNA polymerase stalled at initiation and at elongation. Finally, structural models of RNA polymerase complexes predicted that, as the growing RNA product becomes longer than ~15 nucleotides, sigma must be "pushed out" of the holoenzyme, since there is a steric clash between RNA and a sigma domain. However, σ70 can remain attached in complex with the core RNA polymerase in early elongation and sometimes throughout elongation. Indeed, the phenomenon of promoter-proximal pausing indicates that sigma plays roles during early elongation. All studies are consistent with the assumption that promoter escape reduces the lifetime of the sigma-core interaction from very long at initiation (too long to be measured in a typical biochemical experiment) to a shorter, measurable lifetime upon transition to elongation.

Sigma cycle
It had long been thought that the sigma factor obligatorily leaves the core enzyme once it has initiated transcription, allowing it to link to another core enzyme and initiate transcription at another site. Thus, the sigma factor would cycle from one core to another. However, fluorescence resonance energy transfer was used to show that the sigma factor does not obligatorily leave the core. Instead, it changes its binding with the core during initiation and elongation. Therefore, the sigma factor cycles between a strongly bound state during initiation and a weakly bound state during elongation.

Sigma factor competition
The number of RNAPs in bacterial cells (e.g., E. coli) have been shown to be smaller than the number of sigma factors. Consequently, if a certain sigma factor is overexpressed, not only will increase the expression levels of genes whose promoters have preference for that sigma factor, but it will also reduce the probability that genes with promoters with preference for other sigma factors.

Meanwhile, transcription initiation has two major rate limiting steps: the closed and the open complex formation. However, only the dynamics of the first step depends on the concentration of sigma factors. Interestingly, the fastest is the closed complex formation relative to the open complex formation, the less responsive is a promoter to changes in sigma factors’ concentration (see for a model and empirical data of this phenomenon).

Genes with dual sigma factor preference
While most genes of E. coli can be recognized by an RNAP with one and only one type of sigma factor (e.g. sigma 70), a few genes (~ 5%) have what is called a “dual sigma factor preference”, that is, they can respond to two different sigma factors, as reported in RegulonDB. The most common ones are those promoters that can respond to both sigma 70 and to sigma 38 (iIlustrated in the figure). Studies of the dynamics of these genes showed that when the cells enter stationary growth they are almost as induced as those genes that have preference for σ38 alone. This induction level was shown to be predictable from their promoter sequence. A model of their dynamics is shown in the figure. In the future, these promoters may become useful tools in synthetic genetic constructs in E. coli.

title: Sigma factor


text:
Bishop of Blackburn

The Bishop of Blackburn is the Ordinary of the Church of England Diocese of Blackburn in the Province of York.

The diocese covers much of the county of Lancashire and has its see in the town of Blackburn, where the seat of the diocese is located at the Cathedral Church of Saint Mary. Despite having a cathedral Blackburn is not a city.

The office has existed since the foundation of the see from part of the Diocese of Manchester in 1926 under George V. The current bishop is Philip North, since the confirmation on 25 April 2023 of his election. The bishop's residence is Bishop's House, Salesbury.

Assistant bishops
Among those who have served as assistant bishops in the diocese were:
 * 1982 – 1999 (d.): Ken Giggall (former Bishop of St Helena and Auxiliary Bishop of Gibraltar) retired to Lytham
 * 1992 – 2000 (ret.): Donald Nestor, Priest-in-Charge of Bretherton and former Suffragan Bishop of Lesotho

title: Bishop of Blackburn


text:
Bishop of Bradford

The Bishop of Bradford is an episcopal title used by a suffragan bishop of the Church of England Diocese of Leeds, in the Province of York, England. The title takes its name after Bradford, a city in West Yorkshire.

Upon the creation of the Diocese of Leeds on 20 April 2014, the diocesan see was dissolved and its diocese's territory added to the new diocese, within which there is a newly created suffragan see for the Area Bishop of Bradford. On 26 August 2014, it was announced that Toby Howarth was to become the first area bishop of Bradford; he was consecrated on 17 October 2014.

title: Bishop of Bradford


text:
Muldraugh Hill

Muldraugh Hill is an escarpment in Bullitt, Hardin, Jefferson, and Nelson counties of central Kentucky separating the Bluegrass on the north and north-east from the Pennyrile on the south and south-west. This escarpment fades into the Pottsville Escarpment on the east and terminates at the Ohio River in the west. However, in truth, it continues in Indiana as Floyds Knobs.

In parts of its eastern stretches, Muldraugh Hill is little more than a slight hill, but in some of the western areas, it is represented by extensive areas of knobs. This landform consists mostly of siltstones and shales, with some minor limestones, lying between the limestones and dolomites of the older Bluegrass and the limestones of the newer Pennyrile. Rock outcrops are minor except where the overlying limestones are exposed in the north of Fort Knox.

The Jefferson Memorial Forest in Louisville, Kentucky and Bernheim Forest in Bullitt and Nelson Counties are both located within the knobs of Muldraugh Hill, as is part of Fort Knox.

title: Muldraugh Hill


text:
University of Bridgeport

The University of Bridgeport (UB or UBPT) is a private university in Bridgeport, Connecticut. The university is accredited by the New England Commission of Higher Education. In 2021, the university was purchased by Goodwin University; it retained its own name, brand, and board of trustees.

Founded originally as the Junior College of Connecticut, it is the only university in Bridgeport and one of the largest in Connecticut. The university offers more than 60 degree programs to over 5,000 students at the bachelor's, master's, and doctoral levels. This includes the only Chinese medicine program in Connecticut; one of two, along with University of Connecticut, medical laboratory sciences programs in Connecticut; and one of the few chiropractic schools on the East Coast. The university hosted a program in naturopathic medicine until it was discontinued in 2019.

E. Everett Cortright, Alfred Fones, and former Raybestos President Sumner Simpson opened the Junior College of Connecticut, the first of its kind in the Northeastern United States. The school purchased the former P. T. Barnum estate and neighboring property adjacent to Seaside Park and became a four-year institution in 1947, when it was renamed the University of Bridgeport.

Origins
The university began in 1927 as the first junior college in Connecticut. Founders E. Everett Cortright, Alfred Fones, and Sumner Simpson saw a need in Bridgeport, then one of only six American cities of more than 100,000 residents lacking a college or university. The school expanded significantly, adding dormitories and a school of business. The school purchased the former P. T. Barnum estate and neighboring property adjacent to Seaside Park and became a four-year institution in 1947, when it was renamed the University of Bridgeport.

Naming and development
Founder and first President Everett Cortright and Alfred Civillion Fones chartered the Junior College of Connecticut in November 1927 to expand the academic opportunities for local Connecticut youth. It was the first junior college chartered in the Northeastern United States. Cortright, the former superintendent of schools in Bridgeport and a professor of education at Columbia University, knew there was a great desire for higher education, given there were no colleges easily accessible to people in the region.

On the twentieth anniversary of the Junior College of Connecticut in 1947, the governor of Connecticut chartered the institution as a four-year university with authority to grant the baccalaureate degree. By that time, the P.T. Barnum estate at Seaside Park had been purchased. The Junior College of Connecticut was retained and the College of Arts and Sciences and the Colleges of Business Administration were established at once. These were followed soon after by the Colleges of Nursing, Education and Engineering. The legislature of Connecticut acknowledged the school's growth by renaming the institution "University of Bridgeport" in 1947.

The university's merger with the Weylister Secretarial Junior College of Milford, Connecticut, afforded additional expansion. The school became a division of the Junior College of Connecticut, as did the Fones School of Dental Hygiene which, at its inception in 1949, was the only such school in Connecticut and the second in New England.

The school began awarding master's degrees in 1951. Under President James Halsey, the university was among the first American universities to enroll a significant number of international students. In 1953, Arnold College merged with and was incorporated into the College of Education. Founded in 1886, Arnold was the oldest co-educational school of physical education in the United States. It was directed for many years by E. Herman Arnold, an eminent and pioneering educator.

The university had moved all of its operations from its Fairfield Avenue location to the campus at Seaside Park by 1950. There it occupied 22 acres of land that now has grown to 52 acres. An enrollment of almost 3,500 students included the first influx of international students. The university awarded its first master's degree in 1951 and its first doctoral program in Educational Leadership in 1979, and added a Ph.D. degree program in Computer Science and Engineering in 2006. Two terminal, professional, alternative medicine programs in Chiropractic and Naturopathic Medicine were established in 1991 and 1996 respectively. The naturopathic medicine program was discontinued in 2019.

Affilitation with the Unification Church
In 1990, after severe endowment losses, discussion began about affiliating or possibly merging the university with either the University of New Haven or Sacred Heart University. The university was approached by the Professors World Peace Academy (PWPA), an affiliate of the Unification Church, but its offer to bail out the university was spurned by the trustees who said the school was "not going to have anything to do with the offer" and were concerned that such an affiliation would damage the university's reputation.

Problems continued to plague the university; enrollment fell to 1,300 in 1991. Debt rose to over $22 million in 1991–92. Serious plans to merge the university with Sacred Heart fell through in 1992; the law school instead wanted to associate with Quinnipiac University, but Sacred Heart maintained that any takeover would have to include the Law School. There were other universities willing to take over the school, but were unwilling to take on its debt. The university's charter required the trustees to enter into "serious negotiations", and they accepted the offer, giving the PWPA sixteen spots as trustees, constituting a majority. The PWPA invested $50.5 million in the university on May 30, 1992, enabling the university to keep its accreditation.

A two-year faculty strike, started in the midst of the university's financial troubles, intensified when the trustees gave control to the PWPA. Eventually, sixty-six professors and librarians agreed to a "divorce" with the university in return for compensation of up to a year's salary. In a similar move, the Law School decided to cut ties with the university, separating from it. In order for the law school to remain open it had to merge with a financially sound university. The law school faculty and students voted to merge with Quinnipiac University and the name was officially changed to the Quinnipiac University School of Law.

Once PWPA-appointed trustees constituted a majority on the board of trustees, the trustees retained the president at the time, Edwin G. Eigel, Jr. (1932–2008). Eigel served as president until 1995. He was succeeded by distinguished Holocaust scholar, professor emeritus at Florida State, and former PWPA president Richard L. Rubenstein, who served from 1995 to 1999. Neil Albert Salonen, a member of the Unification Church, was the chairman of the university's board of trustees when he was chosen to serve as ninth University president in 1999. He had earlier managed several Unification Church related organizations, and had served as president of the Unification Church of the United States from 1973 to 1980, and as chairman of the International Cultural Foundation, prior to becoming the chief executive of the university. Salonen retired in 2018.

Since 2003 the university has been financially independent from PWPA after having received funding from the PWPA from 1992 until 2002. It has remained non-sectarian throughout. Turnover on the board of trustees had led, over time, to a very different composition, when compared to the 1991 board. As he retired, Salonen stated that "2 or 3" members of the board of trustees were church members. Under his successor, Laura Skandera Trombley, the board of trustees was enlarged to 36 members. She announced, in an email to faculty, staff, and students on May 24, 2019, that "During the May 17 meeting of the UB Board of Trustees, the body unanimously voted to amend the university's bylaws to remove any references to and governance rights of the Professors World Peace Academy, an affiliate of the Unification Church...This amendment finalizes a termination process, which was long under way. The board expressed its gratitude for previous support."

Present day
Enrollment grew from 1,383 total students in 1992 to 5,323 students in fall 2008, a trend which continued throughout the decade, with 5,434 students enrolled in fall 2018. In 1991, the school added a chiropractic program, the first university-affiliated program of its kind in the U.S. Additional doctoral programs in naturopathic medicine and computer science and engineering were added in 1996 and 2006. The Physician Assistant Institute matriculated its first class at the university in January 2011. In 2014, the school partnered with the Peace Corps to offer New England's first Peace Corps Preparatory Program. In 2014, the School of Nursing at Bridgeport Hospital began a merger with the university which was completed over the next few years.

As of 2014, the university consisted of thirteen schools, institutes and colleges:

In 2018, the university reorganized these colleges and schools into three colleges (with constituent programs and schools), in order to encourage interdisciplinary collaboration, streamline administrative channels, and create clarity and identity for current and potential students:
 * School of Arts and Sciences
 * Ernest C. Trefz School of Business
 * College of Public and International Affairs (CPIA)
 * School of Engineering
 * Shintaro Akatsu School of Design (SASD)
 * Fones School of Dental Hygiene
 * School of Continuing and Professional Studies
 * College of Chiropractic
 * School of Education
 * College of Naturopathic Medicine
 * Acupuncture Institute (UBAI)
 * Nutrition Institute
 * Physician Assistant Institute (PAI)
 * School of Nursing (In April 2014 the University of Bridgeport and Bridgeport Hospital announced an agreement to absorb the Bridgeport Hospital School of Nursing into the university, forming the University of Bridgeport School of Nursing.)

 * The College of Arts & Sciences
 * The College of Business, Education, & Engineering
 * The College of Health Sciences

On July 25, 2019, the University of Bridgeport and Marlboro College announced plans to enter into a merger that would create an expanded university with deeper connections between professional programs and the liberal arts. It was announced in September 2019 that the merger was no longer in the works. On April 2, 2020, Laura Skandera Trombley resigned as president to assume the presidency of Southwestern University in Texas. Provost Stephen Healey was appointed interim president, and Tarek Sobh, vice president for research & economic development and dean of the College of Business, Education, and Engineering, was appointed interim provost.

In 2019, the university announced that the College of Naturopathic Medicine would be discontinued.

In January 2021, it was announced that the non-profit Goodwin University would be taking over the University of Bridgeport, and operating it as a subsidiary, although UB would retain its own name and brand. Two months later, Paier College (formerly Paier College of Art) announced plans to move its campus to Bridgeport, into facilities formerly used by the University of Bridgeport, before the start of the fall 2021 session.

Region and campus
The stately old Victorian homes on campus date from the late 1800s to the early 1900s, some owned by leading area industrialists and some by family and friends of showman P. T. Barnum. The university has restored two of the homes, and done substantial work on a third. These homes, as well as a newer 1937 home in International style, form the Marina Park Historic District, which is on the National Register of Historic Places.

Academics
The University of Bridgeport is accredited by the New England Association of Schools and Colleges. The university is also accredited by the board of governors of the Connecticut Department of Higher Education.

Academic programs range from associate degrees in areas such as Business Administration and Dental Hygiene, to Bachelor of Arts, Bachelor of Fine Arts, Bachelor of Music, and Bachelor of Science degrees in areas such as Accounting, Psychology, Graphic Design, Computer Science, Mathematics, Biology, Music, Computer Engineering, and International Business. The school also offers master's and doctoral programs in areas such as business, counseling, engineering, and education. UB also has adult and continuing education/distance learning programs on their main campus, as well as their Waterbury branch campus, with a total of 125 different programs of study.

For undergraduates, as of 2004, the school started an honors program that allows for the awarding of an honors degree upon graduation, if certain honors course requirements and academic standards (such as a cumulative grade point average of at least 3.0) have been maintained. The program also offers additional course options to students enrolled in the honors program.

In its 2012 rankings, University of Bridgeport placed in Tier 2 of National Universities, by U.S. News & World Report, with a 57.5% acceptance rate. According to the university's website incoming students had an average GPA of 3.0, and an average SAT score of 1000 (Math and Verbal), 80% went on to get a master's degree.

In 2006, The Washington Monthly ranked University of Bridgeport 147th of all 245 National universities, with criteria based on research, community service, and social mobility.

In its 2013 rankings, the online graduate computer information technology program was ranked #4 by U.S. News & World Report and it was ranked # 1 in its 2012 rankings while the online bachelor's degree program at UB was ranked #12. The online master's degree in engineering was also ranked #16 in 2013.

In 2021, University of Bridgeport was ranked #298–#389 in National Universities by U.S. News & World Report.

Athletics
The University of Bridgeport competes in NCAA Division II athletics and has eight women's sports, and five men's sports. The Women's Soccer Team were the 2018 National NCAA Division II Champions.

Greek life
Recognized fraternities and sororities at the university include:

Campus safety
Around 2000, to address safety concerns both on and off-campus, the university instituted a program where students are issued a portable alarm unit (PAL) that pinpoints their position and enables campus security to get to them in under two minutes. This system works immediately on the university campus, and in the neighborhood surrounding campus. Further, the Campus Security Department has 40 unarmed personnel that provide security services 24 hours a day, with both on-foot and on-bicycle patrols. In 2018, in the midst of a rapid gentrification in the neighborhood surrounding the campus, the global security firm ADT ranked UB as the safest campus in Connecticut. In 2019, the university discontinued the use of PALs in favor of the LiveSafe app for mobile devices.

Palmetto
In front of the Eleanor N. Dana Hall at the College of Naturopathic Medicine, there is a Sabal Palmetto, a small palm about six feet in height with a spread of five feet. This tree is notable for growing so far north from it common cultivation range., which ends at about Virginias eastern shore. What is also notable is it is growing in USDA zone 7a-7b, while palmettos usually grow in 8a and higher. This tree suffered die-back over the harsh 2017-2018 winter and its height was reduced from about 8 feet using the tip of the tallest frond. This Sabal Palmetto was grown from seed from collected in Sun City Center, FL, in 2005. It was planted outside in its current location in 2009 by Eugene Zampieron. It is in a favorable microclimate, very close to a south-facing masonry wall, and is about 500 ft from Long Island Sound with it getting protection each winter. It is listed by Connecticut's Notable Trees website as the first plant of its species and the first palm tree on the database. It is also a Connecticut champion tree.

University seal
Bridgeport's seal combines four core elements of its traditions and distinct character. In the upper left quadrant, the lamp of learning, which has been an element of the official Bridgeport's seal since 1931, is shown. In the upper right quadrant of the seal, the tree of life is shown, symbolizing personal and institutional growth. The lower left shows Bridgeport's seascape, illustrating the university's campus on Long Island Sound. The lower right quadrant shows the Perry Arch, representing tradition, solid foundations, and performance.

Alumni

 * George Dixon, former professional football player, collegiate football coach, and Canadian Football Hall of Fame member
 * Kenichi Ebina, winner of America's Got Talent (season 8)
 * Tommy Edison, YouTuber and radio presenter known for his blindness and internet presence
 * Lee Harry, director
 * Henry Buttelmann, flying ace during the Korean and Vietnam War
 * Michael J. Jarjura, mayor of Waterbury, Connecticut
 * Lamont Jones (born 1972), basketball player
 * David Mosser, biologist
 * George Logan, member of the Connecticut Senate from the 17th district
 * Rodrigo Paz, Businessman
 * Norman Taylor, basketball player
 * Bill Smitrovich, actor
 * Dave Weckl, jazz drummer
 * Tom Shopay, left-handed hitter who played outfielder for the New York Yankees
 * Irwin Chusid, journalist, music historian, radio personality, and record producer
 * Ernesto Pernia, former Director-General of the National Economic and Development Authority
 * Mark Lasky, cartoonist known for having succeeded Ernie Bushmiller on Nancy
 * Jerry Penacoli, host with the US syndicated magazine show Extra
 * Joe Tacopina, attorney
 * Faisal Shahzad, terrorist
 * Kenneth P. Weiss, Entrepreneur

Faculty

 * Robert V. Bruce, 1988 winner of the Pulitzer Prize for History
 * Bill Finegan, jazz bandleader, pianist, arranger, and composer.
 * Seth Roland (born 1957), soccer player and coach
 * Sal Salvador, bebop jazz guitarist and music educator.
 * James Shomate, pianist
 * Igor Sikorsky, aviation pioneer
 * Clark L. Wilson, psychologist
 * John Worley, saxophonist
 * Denis Collins, business ethicist
 * Douglas Townsend, composer and musicologist
 * Tarek Sobh, former Dean of the College of Engineering, Business, and Education of the University of Bridgeport, current president of Lawrence Technological University
 * Lili Qiu, computer scientist known for her research on wireless networks

title: University of Bridgeport


text:
La Blue Girl

La Blue Girl (淫獣学園 La☆Blue Girl) is an erotic anime and manga series by Toshio Maeda. Like Maeda's other hentai series (e.g., Urotsukidōji), La Blue Girl features a large amount of tentacle rape. It departs somewhat from its predecessors, however, by lightening the atmosphere with humor, lightly parodying the "tentacle hentai" genre.

An immensely successful series, La Blue Girl has inspired, over the years, several OVA series for a total of 14 episodes, a comic book adaptation, three live action movies, some PC games and some art books.

Story
The story involves various ninja clans in a constant state of war with one another. The female protagonist is Miko Mido, a young ninja-in-training and the next leader of the Miroku ninja clan. This clan has control over the Shikima, a perverted race of sex-hungry demons led by Miko's father, the Shikima Lord. However, when thieves steal the magic compact that grants the clan this power, Miko has to fight the Shikima, utilizing her "sexcraft" ninjutsu in order to save the world. The Shikima live in a parallel dimension called the Shikima Realm, and one must perform specific sexual rituals in order to travel there.

Characters

 * Miko Midō (美童 巫女)
 * Miko is the heroine of all La Blue Girl OVAs and a kunoichi. She is the last descendant of the Miroku kunoichi clan, which has been feuding with the Suzuka clan for many generations. She is often very annoyed at being a sex ninja and having to use her body as a weapon against opponents. Miko can use many unusual sexual techniques, such as hardening her pubic hair into needles and firing them at an opponent, or the 'Nyoninboh' technique which allows her to swell her clitoris to the size of a man's penis and use it to arouse the passions of her female rivals. If strands of her hair are torn out, she can use them as acupuncture needles to stimulate her opponent's erotic pleasure points. Her most powerful attack is the 'Aoi Tatsumaki' (Blue Whirlwind), in which her hair turns into a giant blue tornado that invariably rips away all of her clothing (although most of her clothing is invariably in tatters by the time she employs this climactic tactic anyway). Miko is the daughter of Seikima, the King of the Shikima, and of Maria, the Queen, who is human and a former Miroku woman. As such, Miko is a demon-half-breed and has the blue-colored blood of the Shikima, hence the title La Blue Girl.
 * Miko is the heroine of all La Blue Girl OVAs and a kunoichi. She is the last descendant of the Miroku kunoichi clan, which has been feuding with the Suzuka clan for many generations. She is often very annoyed at being a sex ninja and having to use her body as a weapon against opponents. Miko can use many unusual sexual techniques, such as hardening her pubic hair into needles and firing them at an opponent, or the 'Nyoninboh' technique which allows her to swell her clitoris to the size of a man's penis and use it to arouse the passions of her female rivals. If strands of her hair are torn out, she can use them as acupuncture needles to stimulate her opponent's erotic pleasure points. Her most powerful attack is the 'Aoi Tatsumaki' (Blue Whirlwind), in which her hair turns into a giant blue tornado that invariably rips away all of her clothing (although most of her clothing is invariably in tatters by the time she employs this climactic tactic anyway). Miko is the daughter of Seikima, the King of the Shikima, and of Maria, the Queen, who is human and a former Miroku woman. As such, Miko is a demon-half-breed and has the blue-colored blood of the Shikima, hence the title La Blue Girl.

 * Nin-Nin (ニン忍)
 * Nin-Nin is a dwarf ninja who is always hooded. He is Miko's loyal, yet sexually perverted, companion and sidekick. He likes to peep when Miko is bathing or masturbating and beams with joy whenever he can see her naked, barely dressed, or in any troublesome sexual encounter with demons or other ninja. On the other hand, he takes seriously to heart his role as Miko's protector and always try to help her out whenever she is in trouble, or at least whenever he is not busy taping her "exploits" for future reference.
 * Nin-Nin is a dwarf ninja who is always hooded. He is Miko's loyal, yet sexually perverted, companion and sidekick. He likes to peep when Miko is bathing or masturbating and beams with joy whenever he can see her naked, barely dressed, or in any troublesome sexual encounter with demons or other ninja. On the other hand, he takes seriously to heart his role as Miko's protector and always try to help her out whenever she is in trouble, or at least whenever he is not busy taping her "exploits" for future reference.

 * Fubuki Kai (甲斐 吹雪)
 * A self-made ninja, Fubuki Kai sees Miko Mido as her adversary, as she wishes to prove that she is more talented than her, and more worthy of the title of headmaster of the Miroku ninja clan. After she is defeated by Miko in a sexual duel, however, she is adopted by the Shikima and becomes a friend of Miko. When adopted by the Shikima, she metamorphoses into a Shikima, since she desired enough power to equal Miko Mido. She is fond of her new form, but also irritates Miko by being better than her.
 * A self-made ninja, Fubuki Kai sees Miko Mido as her adversary, as she wishes to prove that she is more talented than her, and more worthy of the title of headmaster of the Miroku ninja clan. After she is defeated by Miko in a sexual duel, however, she is adopted by the Shikima and becomes a friend of Miko. When adopted by the Shikima, she metamorphoses into a Shikima, since she desired enough power to equal Miko Mido. She is fond of her new form, but also irritates Miko by being better than her.

 * Yaku (夜久)
 * Yaku is another ninja of the Miroku clan, whom Miko meets when she decides to travel to the secret Miroku village. She is the only survivor (with Miko) of the Miroku massacre caused by Kamiri and Kugutsumen. Yaku is a powerful—and potentially very threatening—girl, for she shapeshifts into a werewolf unless she reaches an orgasm in time. Her most notable other attributes are her large breasts, of which Miko is envious.
 * Yaku is another ninja of the Miroku clan, whom Miko meets when she decides to travel to the secret Miroku village. She is the only survivor (with Miko) of the Miroku massacre caused by Kamiri and Kugutsumen. Yaku is a powerful—and potentially very threatening—girl, for she shapeshifts into a werewolf unless she reaches an orgasm in time. Her most notable other attributes are her large breasts, of which Miko is envious.

 * Kamiri
 * Kamiri was at one time the Miroku clan's sexcraft instructor, but she was banished by the clan for treachery because she became the lover of the renegade ninja Kugutsumen. Before being driven away, she was also punished by being raped with a thorny phallus that mangled her vagina. As a result, she swore to take vengeance on the Miroku clan. When Kamiri returns and steals the Miroku treasure, the magical sword Jipang, its evil spirit possesses her and makes her want to conquer the Shikima Realm, kill King Seikima, and rule over it. For that she needs Miko, who is the only one who knows how to get there. After several fights between Kamiri, Miko and Yaku, Kamiri is destroyed by the evil spirit of Jipang.
 * Kamiri was at one time the Miroku clan's sexcraft instructor, but she was banished by the clan for treachery because she became the lover of the renegade ninja Kugutsumen. Before being driven away, she was also punished by being raped with a thorny phallus that mangled her vagina. As a result, she swore to take vengeance on the Miroku clan. When Kamiri returns and steals the Miroku treasure, the magical sword Jipang, its evil spirit possesses her and makes her want to conquer the Shikima Realm, kill King Seikima, and rule over it. For that she needs Miko, who is the only one who knows how to get there. After several fights between Kamiri, Miko and Yaku, Kamiri is destroyed by the evil spirit of Jipang.

 * Kugutsumen
 * A renegade ninja of the Suzuka clan who became the lover of Kamiri, the Miroku sexcraft instructor, after he was able to take control of her when a drop of his semen entered her body during a fight. It was he who killed all the Miroku ninja by mangling their vaginas and causing fatal hemorrhages, mimicking their punishment of his lover. Because of her wounds and her possession by Jipang's evil spirit, Kamiri refuses to have sex with him and so he rapes several young girls. He is a tough opponent for Miko and Yaku, for he often tricks them by disguising himself and so lures them into his traps.
 * A renegade ninja of the Suzuka clan who became the lover of Kamiri, the Miroku sexcraft instructor, after he was able to take control of her when a drop of his semen entered her body during a fight. It was he who killed all the Miroku ninja by mangling their vaginas and causing fatal hemorrhages, mimicking their punishment of his lover. Because of her wounds and her possession by Jipang's evil spirit, Kamiri refuses to have sex with him and so he rapes several young girls. He is a tough opponent for Miko and Yaku, for he often tricks them by disguising himself and so lures them into his traps.

 * Various Shikima and tentacled monsters
 * The monsters, who generally have irregular and grotesque shapes, try to make the women reach orgasm, to kill the women, or both, depending on the monsters' various agendas and natures (one poltergeist is depicted in the manga as merging with a kappa in order to heal himself after being defeated by Miko and Nin-Nin and thus get revenge against Miko; the Shikima King is said to be Miko's father, but a Shikima curse leads to her being violated anyhow, as two examples).

 * Miyu Mido (美童 美夕)
 * An older sister of Miko and a drama actress, she was kidnapped by the demons from the Shikima World and was rescued by her sister. It is revealed that Miyu was not born of a Shikima but of a human, born through the joining of a member of the Suzuka clan; this disqualified Maria of holding the title of chief of the Miroku clan and, thus, she was driven away, while Miko was given to her grandmother for a proper raising and training.
 * An older sister of Miko and a drama actress, she was kidnapped by the demons from the Shikima World and was rescued by her sister. It is revealed that Miyu was not born of a Shikima but of a human, born through the joining of a member of the Suzuka clan; this disqualified Maria of holding the title of chief of the Miroku clan and, thus, she was driven away, while Miko was given to her grandmother for a proper raising and training.

 * Kanako (香菜子)
 * Introduced in the third episode of La Blue Girl Returns, Kanako is a student at a nursing college. Before her grandmother died, she had trained Kanako in the carnal arts in order to offer her services to Miko Mido and the Miroku clan. It then became her dream to be summoned by Miko, and she developed a crush on her. She got in touch with the other main characters through a website posted by Fubuki in their search for more members of the Miroku clan.

 * Kochō (胡蝶)
 * The leader of the Mahoroba clan.

 * Rokuga
 * Another member of the Mahoroba clan. Posing as Miyu's new boyfriend, he succeeds in stealing the Shikima seal case.

 * Ruri (瑠璃)
 * Miko's classmate.

 * Maho (真帆)
 * Ruri's brother, introduced in the third episode. It is love at first sight between him and Miko, but she continually dreams of him wearing a strange outfit, a hint that they were lovers in the past.

La Blue Girl
Injū Gakuen / La Blue Girl (four episodes, 1992–93) is an adaptation of the original manga. Miko Mido is a teenage girl who is to be the next leader of the ancestral Miroku ninja clan. But the Suzuka clan steals the treasured compact that symbolizes the truce between the Miroku and the Shikima, a race of perverted otherworldly demons, and soon Miko has to use the sexual techniques of the Miroku to survive the assaults of the demons and protect her sister. After learning the truth behind her heritage and the identity of her true parents, she embarks on a journey to become a real Miroku ninja and would have to fight an ex-mistress-turned-traitor of the Miroku clan.

New La Blue Girl
Shin Injū Gakuen / New La Blue Girl (two episodes, 1993) adapts the end of the manga, and as such is a follow-up and the conclusion to Miko's adventures in the first series. This time the enemies are Fubuki Kai, a rogue ninja who wants to defeat Miko and claim the title of best ninja, and the cybernetized survivors of the Suzuka clan. La Blue Girl 6 was initially released on VHS in two 30-minute long semi-episodes, while later releases (including the licensed English one) combine them into an hour long episode.

Lady Blue
Injuu Gakuen EX (淫獣学園EX) a.k.a. Lady Blue (four episodes, 1994). Features an original story about two ghosts, Kyoshiro and Shanahime, harboring an old grudge against the Shikima and attacking several of Miko's friends, including her first love.

Lady Blue is about Miko's first love. Miko meets a young man named Hidemasa outside her apartment building and falls in love at first sight. Just when Miko thinks she can finally live like a normal girl and enjoy being in love, a mysterious female phantom appears in her school, sucking the life out of Miko's pretty young schoolmates. Fubuki reports that something is very wrong in the Shikima realm. Miko's parents are being tortured by the sound of flutes playing and no one knows why.

Miko and Fubuki investigate and find out that there is actually a love story behind it all, for the flutes belonged to a betrothed couple (Kyoshiro and Shanahime) 400 years ago, but treachery got in the way, so their love was never realized. The flutes are now cursed and Miko's dream guy, Hidemasa, is kidnapped by the vengeful phantom of Shanahime in order to resurrect her Kyoshiro.

Compilation episodes
The first was a 90 minute compilation video of the first 4 episodes titled 'Climax Taizen', a 60 minute compilation video of the 'Shin' series titled 'Ecstasy Taizen' and a 60 minute compilation video of the 'EX' series. Included in the 'Injuu Gakuen La☆Blue Girl Memorial Collection' LD-Box set.

La Blue Girl Returns

Injuu Gakuen Fukkatsu-hen (淫獣学園 復活篇) a.k.a. La Blue Girl Returns (four episodes, 2001) is an anime series that continues the adventures of Miko Mido. Another original story, this time about the legendary Shikima Brain, a place rumored to bring total power over the universe. It is coveted by the insectoid ninja clan of the Mahoroba and protected by a mysterious clan, who may have a relation with Miko's previous life.

The plot begins when a race of butterfly-like demons named the Mahoroba want to enslave Miko Mido and her sister to steal the seal case that controls the Shikima. Their ultimate goal is to conquer the Shikima Brain, a legendary place of the Shikima realm which is said to confer the power to rule the universe.

Censorship issues
Censorship is practiced differently both in Japan and in the U.S. due to their different laws: Japanese law technically discourages showing of genital hair or explicit genitalia, while the United States is more concerned about forbidding the display of sexual acts involving people under 18. Hence, there are censoring mosaics in Japan and scene removals and different ages of characters in the U.S.

While not featuring the censoring mosaics of the original Japanese version, the U.S. release of La Blue Girl was edited during the initial VHS release and all scenes featuring Miko's companion Nin-Nin engaged in a sexual act were removed, probably to avoid the charge of hebephilia.

For similar reasons, the age of the heroine was also altered: initially stated to be a 16-year-old high-schooler in the original Japanese version, she is an 18-year-old college student in the U.S. version. The various U.S. DVD releases contain this edited version.

In the U.K., the British Board of Film Classification famously refused to give it a certificate; meaning it was banned from release in the region.

Live action movies

 * Injū Gakuen: Shikima-kai no gyakushū (Revenge of the Sex Demon King) (1994)
 * Injū Gakuen 2: Mashō no hime tanjō jissha-hen (Birth of the Demon Child) (1996)
 * Injū Gakuen 3: Kunoichi-gari (Lady Ninja) (1996)

Printed material

 * La Blue Girl, Toshio Maeda's manga of six volumes.
 * La Blue Girl, a U.S. comic book by Matt Lunsford and José Calderon. It has the distinction of retelling the two distinctly separate story arcs of the first four episodes of the first anime series by merging them together, albeit with story changes to the plots of episodes 2 to 4. Whereas Toshio Maeda's manga established him to be a young Shikima demon able to transform into an adult form, the U.S. series reveals that he is a product of his human mother's rape by a Shikima, that she died giving birth to him, and that his dual heritage resulted in his deformed face, which is shown unmasked.
 * The Graffiti book, a compilation of screenshots from episodes 1 to 4.
 * The In no Shou and You no Shou art books contain screenshots and illustrations from La Blue Girl and Lady Blue.
 * The Art Book of Injuu Gakuen / Youjuu Kyoushitu contains CG illustrations from the PC98 game.
 * Rin Shin's art book contains illustrations used for the promotion of the series.
 * A novelization of the OVA series (two volumes for episodes 1–5, and two volumes for the EX series) features a completely different plot, different characters (most notably the Ranmaru-Bosatsu duo) and a more sexualized and violent tone than the original.

Video games

 * La Blue Girl for NEC PC-9801 and FM-Towns, featuring a different character design from the manga and the anime. The story is an adaptation of both the first volume of the manga and OVA: Miko's friends at school are assaulted by demons and her professor is kidnapped and sent to their infernal dimension; Miko travels there and saves her; everyone goes back to Earth, where a final showdown is awaiting Miko at school. Gameplay-wise, it is a "digital comics" adventure game with some shooting phases (in a Snatcher fashion, and with shuriken instead of a pistol).
 * La Blue Girl for Windows 95. The art is more faithful to the anime character design, while the story is an adaptation of the La Blue Girl EX OVA.

title: La Blue Girl