History.

Protease inhibitory activity in blood plasma was first reported in the late 1800s, but it was not until the 1950s that the serpins antithrombin and alpha 1-antitrypsin were isolated. Initial research focused on their role in human disease: alpha 1-antitrypsin deficiency is one of the most common genetic disorders, causing emphysema, and antithrombin deficiency results in thrombosis.  In the 1980s, it became clear that these inhibitors were part of superfamily of related proteins that included both protease inhibitors (e.g. alpha 1-antitrypsin) and non-inhibitory members (e.g. ovalbumin). The name "serpin" was coined based on the most common activity of the superfamily (serine protease inhibitors). Around the same time, the first structures were solved for serpin proteins (first in the relaxed, and later in the stressed conformation). The structures indicated that the inhibitory mechanism involved an unusual conformational change and prompted the subsequent structural focus of serpin studies.  Over 1000 serpins have now been identified, including 36 human proteins, as well as molecules in all kingdoms of life—animals, plants, fungi, bacteria, and archaea—and some viruses. In the 2000s, a systematic nomenclature was introduced in order to categorise members of the serpin superfamily based on their evolutionary relationships. Serpins are therefore the largest and most diverse superfamily of protease inhibitors.

Activity.

Most serpins are protease inhibitors, targeting extracellular, chymotrypsin-like serine proteases. These proteases possess a nucleophilic serine residue in a catalytic triad in their active site. Examples include thrombin, trypsin, and human neutrophil elastase. Serpins act as irreversible, suicide inhibitors by trapping an intermediate of the protease's catalytic mechanism.  Some serpins inhibit other protease classes, typically cysteine proteases, and are termed "cross-class inhibitors". These enzymes differ from serineproteases in that they use a nucleophilic cysteine residue, rather than a serine, in their active site. Nonetheless, the enzymatic chemistry is similar, and the mechanism of inhibition by serpins is the same for both classes of protease. Examples of cross-class inhibitory serpins include serpin B4 a squamous cell carcinoma antigen 1 (SCCA-1) and the avian serpin myeloid and erythroid nuclear termination stage-specific protein (MENT), which both inhibit papain-like cysteine proteases.

Biological function and localization.

Protease inhibition.

Approximately two-thirds of human serpins perform extracellular roles, inhibiting proteases in the bloodstream in order to modulate their activities. For example, extracellular serpins regulate the proteolytic cascades central to blood clotting (antithrombin), the inflammatory and immune responses (antitrypsin, antichymotrypsin, and C1-inhibitor) and tissue remodelling (PAI-1). By inhibiting signalling cascade proteases, they can also affect development. The table of human serpins (below) provides examples of the range of functions performed by human serpin, as well as some of the diseases that result from serpin deficiency.  The protease targets of intracellular inhibitory serpins have been difficult to identify, since many of these molecules appear to perform overlapping roles. Further, many human serpins lack precise functional equivalents in model organisms such as the mouse. Nevertheless, an important function of intracellular serpins may be to protect against the inappropriate activity of proteases inside the cell. For example, one of the best-characterised human intracellular serpins is Serpin B9, which inhibits the cytotoxic granule protease granzyme B. In doing so, Serpin B9 may protect against inadvertent release of granzyme B and premature or unwanted activation of cell death pathways.  Some viruses use serpins to disrupt protease functions in their host. The cowpox viral serpin CrmA (cytokine response modifier A) is used in order to avoid inflammatory and apoptotic responses of infected host cells. CrmA increases infectivity by suppressing its host's inflammatory response through inhibition of IL-1 and IL-18 processing by the cysteine protease caspase-1. In eukaryotes, a plant serpin inhibits both metacaspases and a papain-like cysteine protease.

Non-inhibitory roles.

Non-inhibitory extracellular serpins also perform a wide array of important roles. Thyroxine-binding globulin and transcortin transport the hormones thyroxine and cortisol, respectively. The non-inhibitory serpin ovalbumin is the most abundant protein in egg white. Its exact function is unknown, but it is thought to be a storage protein for the developing foetus. Heat shock serpin 47 is a chaperone, essential for proper folding of collagen. It acts by stabilising collagen's triple helix whilst it is being processed in the endoplasmic reticulum.  Some serpins are both protease inhibitors and perform additional roles. For example, the nuclear cysteine protease inhibitor MENT, in birds also acts as a chromatin remodelling molecule in a bird's red blood cells.

Structure.

All serpins share a common structure (or fold), despite their varied functions. All typically have three β-sheets (named A, B and C) and eight or nine α-helices (named hA–hI). The most significant regions to serpin function are the A-sheet and the reactive centre loop (RCL). The A-sheet includes two β-strands that are in a parallel orientation with a region between them called the'shutter', and upper region called the 'breach'. The RCL forms the initial interaction with the target protease in inhibitory molecules. Structures have been solved showing the RCL either fully exposed or partially inserted into the A-sheet, and serpins are thought to be in dynamic equilibrium between these two states. The RCL also only makes temporary interactions with the rest of the structure, and is therefore highly flexible and exposed to the solvent.  The serpin structures that have been determined cover several different conformations, which has been necessary for the understanding of their multiple-step mechanism of action. Structural biology has therefore played a central role in the understanding of serpin function and biology.

Conformational change and inhibitory mechanism.

Inhibitory serpins do not inhibit their target proteases by the typical competitive ("lock-and-key") mechanism used by most small protease inhibitors (e.g. Kunitz-type inhibitors). Instead, serpins use an unusual conformational change, which disrupts the structure of the protease and prevents it from completing catalysis. The conformational change involves the RCL moving to the opposite end of the protein and inserting into β-sheet A, forming an extra antiparallel β-strand. This converts the serpin from a stressed state, to a lower-energy relaxed state (S to R transition).  Serine and cysteine proteases catalyse peptide bond cleavage by a two-step process. Initially, the catalytic residue of the active site triad performs a nucleophilic attack on the peptide bond of the substrate. This releases the new N-terminus and forms a covalent ester-bond between the enzyme and the substrate. This covalent complex between enzyme and substrate is called an acyl-enzyme intermediate. For standard substrates, the ester bond is hydrolysed and the new C-terminus is released to complete catalysis. However, when a serpin is cleaved by a protease, it rapidly undergoes the S to R transition before the acyl-enzyme intermediate is hydrolysed. The efficiency of inhibition depends on fact that the relative kinetic rate of the conformational change is several orders of magnitude faster than hydrolysis by the protease.  Since the RCL is still covalently attached to the protease via the ester bond, the S to R transition pulls protease from the top to the bottom of the serpin and distorts the catalytic triad. The distorted protease can only hydrolyse the acyl enzyme intermediate extremely slowly and so the protease remains covalently attached for days to weeks. Serpins are classed as irreversible inhibitors and as suicide inhibitors since each serpin protein permanently inactivates a single protease, and can only function once.

Allosteric activation.

The conformational mobility of serpins provides a key advantage over static lock-and-key protease inhibitors. In particular, the function of inhibitory serpins can be regulated by allosteric interactions with specific cofactors. The X-ray crystal structures of antithrombin, heparin cofactor II, MENT and murine antichymotrypsin reveal that these serpins adopt a conformation wherein the first two amino acids of the RCL are inserted into the top of the A β-sheet. The partially inserted conformation is important because co-factors are able to conformationally switch certain partially inserted serpins into a fully expelled form. This conformational rearrangement makes the serpin a more effective inhibitor.  The archetypal example of this situation is antithrombin, which circulates in plasma in a partially inserted relatively inactive state. The primary specificity determining residue (the P1 arginine) points toward the body of the serpin and is unavailable to the protease. Upon binding a high-affinity pentasaccharide sequence within long-chain heparin, antithrombin undergoes a conformational change, RCL expulsion, and exposure of the P1 arginine. The heparin pentasaccharide-bound form of antithrombin is, thus, a more effective inhibitor of thrombin and factor Xa. Furthermore, both of these coagulation proteases also contain binding sites (called exosites) for heparin. Heparin, therefore, also acts as a template for binding of both protease and serpin, further dramatically accelerating the interaction between the two parties. After the initial interaction, the final serpin complex is formed and the heparin moiety is released. This interaction is physiologically important. For example, after injury to the blood vessel wall, heparin is exposed, and antithrombin is activated to control the clotting response. Understanding of the molecular basis of this interaction enabled the development of Fondaparinux, a synthetic form of Heparin pentasaccharide used as an anti-clotting drug.

Latent conformation.

Certain serpins spontaneously undergo the S to R transition without having been cleaved by a protease, to form a conformation termed the latent state. Latent serpins are unable to interact with proteases and so are no longer protease inhibitors. The conformational change to latency is not exactly the same as the S to R transition of a cleaved serpin. Since the RCL is still intact, the first strand of the C-sheet has to peel off to allow full RCL insertion.  Regulation of the latency transition can act as a control mechanism in some serpins, such as PAI-1. Although PAI-1 is produced in the inhibitory S conformation, it "auto-inactivates" by changing to the latent state unless it is bound to the cofactor vitronectin. Similarly, antithrombin can also spontaneously convert to the latent state, as an additional modulation mechanism to its allosteric activation by heparin. Finally, the N-terminus of tengpin, a serpin from "Thermoanaerobacter tengcongensis", is required to lock the molecule in the native inhibitory state. Disruption of interactions made by the N-terminal region results in spontaneous conformational change of this serpin to the latent conformation.

Conformational change in non-inhibitory functions.

Certain non-inhibitory serpins also use the serpin conformational change as part of their function. For example, the native (S) form of thyroxine-binding globulin has high affinity for thyroxine, whereas the cleaved (R) form has low affinity. Similarly, transcortin has higher affinity for cortisol when in its native (S) state, than its cleaved (R) state. Thus, in these serpins, RCL cleavage and the S to R transition has been commandeered to allow for ligand release, rather than protease inhibition.  In some serpins, the S to R transition can activate cell signalling events. In these cases, a serpin that has formed a complex with its target protease, is then recognised by a receptor. The binding event then leads to downstream signalling by the receptor. The S to R transition is therefore used to alert cells to the presence of protease activity. This differs from the usual mechanism whereby serpins affect signalling simply by inhibiting proteases involved in a signalling cascade.

Degradation.

When a serpin inhibits a target protease, it forms a permanent complex, which needs to be disposed of. For extracellular serpins, the final serpin-enzyme complexes are rapidly cleared from circulation. One mechanism by which this occurs in mammals is via the low-density lipoprotein receptor-related protein (LRP), which binds to inhibitory complexes made by antithrombin, PA1-1, and neuroserpin, causing cellular uptake. Similarly, the "Drosophila" serpin, necrotic, is degraded in the lysosome after being trafficked into the cell by the Lipophorin Receptor-1 (homologous to the mammalian LDL receptor family).

Disease and serpinopathies.

Serpins are involved in a wide array of physiological functions, and so mutations in genes encoding them can cause a range of diseases. Mutations that change the activity, specificity or aggregation properties of serpins all affect how they function. The majority of serpin-related diseases are the result of serpin polymerisation into aggregates, though several other types of disease-linked mutations also occur. The disorder α-Antitrypsin deficiency is one of the most common hereditary diseases.

Inactivity or absence.

Since the stressed serpin fold is high-energy, mutations can cause them to incorrectly change into their lower-energy conformations (e.g. relaxed or latent) before they have correctly performed their inhibitory role.  Mutations that affect the rate or the extent of RCL insertion into the A-sheet can cause the serpin to undergo its S to R conformational change before having engaged a protease. Since a serpin can only make this conformational change once, the resulting misfired serpin is inactive and unable to properly control its target protease. Similarly, mutations that promote inappropriate transition to the monomeric latent state cause disease by reducing the amount of active inhibitory serpin. For example, the disease-linked antithrombin variants "wibble" and "wobble", both promote formation of the latent state.  The structure of the disease-linked mutant of antichymotrypsin (L55P) revealed another, inactive "δ-conformation". In the δ-conformation, four residues of the RCL are inserted into the top of β-sheet A. The bottom half of the sheet is filled as a result of one of the α-helices (the F-helix) partially switching to a β-strand conformation, completing the β-sheet hydrogen bonding. It is unclear whether other serpins can adopt this conformer, and whether this conformation has a functional role, but it is speculated that the δ-conformation may be adopted by Thyroxine-binding globulin during thyroxine release. The non-inhibitory proteins related to serpins can also cause diseases when mutated. For example, mutations in SERPINF1 cause osteogenesis imperfecta type VI in humans.  In the absence of a required serpin, the protease that it normally would regulate is over-active, leading to pathologies. Consequently, simple deficiency of a serpin (e.g. a null mutation) can result in disease. Gene knockouts, particularly in mice, are used experimentally to determine the normal functions of serpins by the effect of their absence.

Specificity change.

In some rare cases, a single amino acid change in a serpin's RCL alters its specificity to target the wrong protease. For example, the Antitrypsin-Pittsburgh mutation (M358R) causes the α1-antitrypsin serpin to inhibit thrombin, causing a bleeding disorder.

Polymerisation and aggregation.

The majority of serpin diseases are due to protein aggregation and are termed "serpinopathies". Serpins are vulnerable to disease-causing mutations that promote formation of misfolded polymers due to their inherently unstable structures. Well-characterised serpinopathies include α1-antitrypsin deficiency (alpha-1), which may cause familial emphysema and sometimes liver cirrhosis, certain familial forms of thrombosis related to antithrombin deficiency, types 1 and 2 hereditary angioedema (HAE) related to deficiency of C1-inhibitor, and familial encephalopathy with neuroserpin inclusion bodies (FENIB; a rare type of dementia caused by neuroserpin polymerisation).  Each monomer of the serpin aggregate exists in the inactive, relaxed conformation (with the RCL inserted into the A-sheet). The polymers are therefore hyperstable to temperature and unable to inhibit proteases. Serpinopathies therefore cause pathologies similarly to other proteopathies (e.g. prion diseases) via two main mechanisms. First, the lack of active serpin results in uncontrolled protease activity and tissue destruction. Second, the hyperstable polymers themselves clog up the endoplasmic reticulum of cells that synthesize serpins, eventually resulting in cell death and tissue damage. In the case of antitrypsin deficiency, antitrypsin polymers cause the death of liver cells, sometimes resulting in liver damage and cirrhosis. Within the cell, serpin polymers are slowly removed via degradation in the endoplasmic reticulum. However, the details of how serpin polymers cause cell death remains to be fully understood.  Physiological serpin polymers are thought to form via domain swapping events, where a segment of one serpin protein inserts into another. Domain-swaps occur when mutations or environmental factors interfere with the final stages of serpin folding to the native state, causing high-energy intermediates to misfold. Both dimer and trimer domain-swap structures have been solved. In the dimer (of antithrombin), the RCL and part of the A-sheet incorporates into the A-sheet of another serpin molecule. The domain-swapped trimer (of antitrypsin) forms via the exchange of an entirely different region of the structure, the B-sheet (with each molecule's RCL inserted into its own A-sheet). It has also been proposed that serpins may form domain-swaps by inserting the RCL of one protein into the A-sheet of another (A-sheet polymerisation). These domain-swapped dimer and trimer structures are thought to be the building blocks of the disease-causing polymer aggregates, but the exact mechanism is still unclear.

Therapeutic strategies.

Several therapeutic approaches are in use or under investigation to treat the most common serpinopathy: antitrypsin deficiency. Antitrypsin augmentation therapy is approved for severe antitrypsin deficiency-related pulmonary emphysema. In this therapy, antitrypsin is purified from the plasma of blood donors and administered intravenously (first marketed as Prolastin). To treat severe antitrypsin deficiency-related disease, lung and liver transplantation has proven effective. In animal models, gene targeting in induced pluripotent stem cells has been successfully used to correct an antitrypsin polymerisation defect and to restore the ability of the mammalian liver to secrete active antitrypsin. Small molecules have also been developed that block antitrypsin polymerisation "in vitro".

Evolution.

Serpins are the most widely distributed and largest superfamily of protease inhibitors. They were initially believed to be restricted to eukaryote organisms, but have since been found in bacteria, archaea and some viruses. It remains unclear whether prokaryote genes are the descendants of an ancestral prokaryotic serpin or the product of horizontal gene transfer from eukaryotes. Most intracellular serpins belong to a single phylogenetic clade, whether they come from plants or animals, indicating that the intracellular and extracellular serpins may have diverged before the plants and animals. Exceptions include the intracellular heat shock serpin HSP47, which is a chaperone essential for proper folding of collagen, and cycles between the cis-Golgi and the endoplasmic reticulum.  Protease-inhibition is thought to be the ancestral function, with non-inhibitory members the results of evolutionary neofunctionalisation of the structure. The S to R conformational change has also been adapted by some binding serpins to regulate affinity for their targets.

Distribution.

Animal.

Human.

The human genome encodes 16 serpin clades, termed serpinA through serpinP, including 29 inhibitory and 7 non-inhibitory serpin proteins. The human serpin naming system is based upon a phylogenetic analysis of approximately 500 serpins from 2001, with proteins named serpinXY, where X is the clade of the protein and Y the number of the protein within that clade. The functions of human serpins have been determined by a combination of biochemical studies, human genetic disorders, and knockout mouse models.

Specialised mammalian serpins.

Many mammalian serpins have been identified that share no obvious orthology with a human serpin counterpart. Examples include numerous rodent serpins (particularly some of the murine intracellular serpins) as well as the uterine serpins. The term uterine serpin refers to members of the serpin A clade that are encoded by the SERPINA14 gene. Uterine serpins are produced by the endometrium of a restricted group of mammals in the Laurasiatheria clade under the influence of progesterone or estrogen. They are probably not functional proteinase inhibitors and may function during pregnancy to inhibit maternal immune responses against the conceptus or to participate in transplacental transport.

Insect.

The "Drosophila melanogaster" genome contains 29 serpin encoding genes. Amino acid sequence analysis has placed 14 of these serpins in serpin clade Q and three in serpin clade K with the remaining twelve classified as orphan serpins not belonging to any clade. The clade classification system is difficult to use for "Drosophila" serpins and instead a nomenclature system has been adopted that is based on the position of serpin genes on the "Drosophila" chromosomes. Thirteen of the "Drosophila" serpins occur as isolated genes in the genome (including Serpin-27A, see below), with the remaining 16 organised into five gene clusters that occur at chromosome positions 28D (2 serpins), 42D (5 serpins), 43A (4 serpins), 77B (3 serpins) and 88E (2 serpins).  Studies on "Drosophila" serpins reveal that Serpin-27A inhibits the Easter protease (the final protease in the Nudel, Gastrulation Defective, Snake and Easter proteolytic cascade) and thus controls dorsoventral patterning. Easter functions to cleave Spätzle (a chemokine-type ligand), which results in toll-mediated signaling. As well as its central role in embryonic patterning, toll signaling is also important for the innate immune response in insects. Accordingly, serpin-27A also functions to control the insect immune response. In "Tenebrio molitor" (a large beetle), a protein (SPN93) comprising two discrete tandem serpin domains functions to regulate the toll proteolytic cascade.

Nematode.

The genome of the nematode worm "C. elegans" contains 9 serpins, all of which lack signal sequences and so are likely intracellular. However, only 5 of these serpins appear to function as protease inhibitors. One, SRP-6, performs a protective function and guards against stress-induced calpain-associated lysosomal disruption. Further, SRP-6 inhibits lysosomal cysteine proteases released after lysosomal rupture. Accordingly, worms lacking SRP-6 are sensitive to stress. Most notably, SRP-6 knockout worms die when placed in water (the hypo-osmotic stress lethal phenotype or Osl). It has therefore been suggested that lysosomes play a general and controllable role in determining cell fate.

Plant.

Plant serpins were amongst the first members of the superfamily that were identified. The serpin barley protein Z is highly abundant in barley grain, and one of the major protein components in beer. The genome of the model plant, "Arabidopsis thaliana" contain 18 serpin-like genes, although only 8 of these are full-length serpin sequences.  Plant serpins are potent inhibitors of mammalian chymotrypsin-like serine proteases "in vitro", the best-studied example being barley serpin Zx (BSZx), which is able to inhibit trypsin and chymotrypsin as well as several blood coagulation factors. However, close relatives of chymotrypsin-like serine proteases are absent in plants. The RCL of several serpins from wheat grain and rye contain poly-Q repeat sequences similar to those present in the prolamin storage proteins of the endosperm. It has therefore been suggested that plant serpins may function to inhibit proteases from insects or microbes that would otherwise digest grain storage proteins. In support of this hypothesis, specific plant serpins have been identified in the phloem sap of pumpkin (CmPS-1) and cucumber plants. Although an inverse correlation between up-regulation of CmPS-1 expression and aphid survival was observed, "in vitro" feeding experiments revealed that recombinant CmPS-1 did not appear to affect insect survival.  Alternative roles and protease targets for plant serpins have been proposed. The "Arabidopsis" serpin, AtSerpin1 (At1g47710; ), mediates set-point control over programmed cell death by targeting the 'Responsive to Desiccation-21' (RD21) papain-like cysteine protease. AtSerpin1 also inhibits metacaspase-like proteases "in vitro". Two other "Arabidopsis" serpins, AtSRP2 (At2g14540) and AtSRP3 (At1g64030) appear to be involved in responses to DNA damage.

Fungal.

A single fungal serpin has been characterized to date: celpin from "Piromyces" spp. strain E2. "Piromyces" is a genus of anaerobic fungi found in the gut of ruminants and is important for digesting plant material. Celpin is predicted to be inhibitory and contains two N-terminal dockerin domains in addition to its serpin domain. Dockerins are commonly found in proteins that localise to the fungal cellulosome, a large extracellular multiprotein complex that breaks down cellulose. It is therefore suggested that celpin may protect the cellulosome against plant proteases. Certain bacterial serpins similarly localize to the cellulosome.

Prokaryotic.

Predicted serpin genes are sporadically distributed in prokaryotes. "In vitro" studies on some of these molecules have revealed that they are able to inhibit proteases, and it is suggested that they function as inhibitors "in vivo". Several prokaryote serpins are found in extremophiles. Accordingly, and in contrast to mammalian serpins, these molecules possess elevated resistance to heat denaturation. The precise role of most bacterial serpins remains obscure, although "Clostridium thermocellum" serpin localises to the cellulosome. It is suggested that the role of cellulosome-associated serpins may be to prevent unwanted protease activity against the cellulosome.

Viral.

Serpins are also expressed by viruses as a way to evade the host's immune defense. In particular, serpins expressed by pox viruses, including cow pox (vaccinia) and rabbit pox (myxoma), are of interest because of their potential use as novel therapeutics for immune and inflammatory disorders as well as transplant therapy. Serp1 suppresses the TLR-mediated innate immune response and allows indefinite cardiac allograft survival in rats. Crma and Serp2 are both cross-class inhibitors and target both serine (granzyme B; albeit weakly) and cysteine proteases (caspase 1 and caspase 8). In comparison to their mammalian counterparts, viral serpins contain significant deletions of elements of secondary structure. Specifically, crmA lacks the D-helix as well as significant portions of the A- and E-helices.

Serpins are a superfamily of proteins with similar structures that were first identified for their protease inhibition activity and are found in all kingdoms of life. The acronym serpin was originally coined because the first serpins to be identified act on chymotrypsin-like serine proteases (serine protease inhibitors). They are notable for their unusual mechanism of action, in which they irreversibly inhibit their target protease by undergoing a large conformational change to disrupt its active site. This contrasts with the more common competitive mechanism for protease inhibitors that bind to and block access to the protease active site.

丝氨酸蛋白酶抑制剂(英语:serpin;serine protease inhibitors)是具有相似结构蛋白质的蛋白质超家族,它是由于蛋白酶抑制活性被识别的,和在生命的各个界被发现的第一个蛋白质超家族。英文缩写丝氨酸蛋白酶抑制剂(英语:serpin)最初被创造,是因为第一个丝氨酸蛋白酶抑制剂对胰凝乳蛋白酶样丝氨酸蛋白酶(丝氨酸蛋白酶抑制剂)将要被识别的行为。它们值得注意的是其动作的不同寻常的机制,它们不可逆地通过经历大的构象改变,扰乱其活性位点抑制它们的靶蛋白酶。与此相反,通过对于结合并阻止访问蛋白酶活性位点的蛋白酶抑制剂是更常见的竞争抑制剂机制。


History.

The name of the church derives from the fact that it replaced a smaller one, that belonged to the Carmelites of the Province of Monte Santo in Sicily. It was built in 1662, on the initiative of Pope Alexander VII, by Cardinal Girolamo Gastaldi, who was later buried there. The original design was the work of Carlo Rainaldi.  The works were interrupted on the dead of the Pontiff in 1667, then resumed in 1673 under the supervision of Gian Lorenzo Bernini and the cooperation of Carlo Fontana and finished in 1679, except for a belfry that was added in the 18th Century.  In July 1825 Pope Leo XII elevated the church to the dignity of Minor basilica.  In this church, on 10 August 1904, Angelo Roncalli, the future Pope John XXIII, was ordained a priest; the event is remembered by a plaque affixed during his pontificate.  Since 1953 the church has become the seat of the "Mass of the artists", a singular initiative conceived in 1941 by presbyter and art historian Ennio Francia; after changing several places for worship, the liturgical event took place in the church in Piazza del Popolo, where every Sunday, for over sixty years, this Eucharistic celebration has been celebrated with representatives of the world of culture and art. It is also in this church that the funeral of people linked to the world of culture and television is often celebrated. For these reasons, it is also known as "Church of the artists".

Description.

The statues of saints on the exterior have been attributed to Bernini's design.  The interior has an elliptical plan, while its so-called "twin" Santa Maria dei Miracoli has a circular plan. It has six side chapels (in the "twin" church they are four). The cupola is dodecagonal.  The first chapel on the left is the "Cappella di Santa Lucia" ("Saint Lucy"). The second chapel, dedicated to St. Mary Magdalene de' Pazzi, was designed by Carlo Rainaldi to honor the Carmelite nun canonized by Pope Clement XI in 1669. The ceiling and the altarpiece of the "Miracle of the Saint" (ca. 1685) was painted by Ludovico Gimignani.  The third chapel is the "Cappella Montioni". The Montioni family commissioned the design to Tommaso Mattei, a pupil of Carlo Fontana. The altarpiece of the "Madonna with Child and Saints Francis and Jacob" (ca. 1687) was completed by Carlo Maratta. The "Assumption" fresco was painted by Giuseppe Chiari. Upon the altar is a modern statue of the "Angel for the artists" by Guelfo (1937–1997).  The presbytery is stuccoed with angels by Filippo Carcani and houses the miraculous 15th-century altarpiece of the "Virgin of Montesanto", which, according to the tradition, was painted by an 11-year-old girl. The sacristy has a frescoed vault with angels and the instruments of passion, the altarpiece of the "Deposition "(ca. 1600) is attributed to Biagio Puccini.  Under the two twin churches are the remains of two pyramid-shaped funerary monuments, which, in shape and size, are very similar to the Pyramid of Cestius and to the demolished Pyramid of Romulus; like these ones, both the tombs probably date back to the Augustan age and served as a monumental entrance to the Campus Martius, precisely the same function that the two churches have today.

Santa Maria in Montesanto is a church of Rome, in the Rione Campo Marzio, which stands in Piazza del Popolo, between Via del Corso and Via del Babuino. It is also known as the Church of the Artists. The church is popularly known as the "twin church" of Santa Maria dei Miracoli, though it shows significant differences especially in the planimetry.

灵迹圣母堂()和圣山圣母堂()是意大利罗马市的两座教堂,都位于人民广场上,面对奥宙连城垣的东北门,即科尔索街在广场上的入口。这两座教堂由于外观非常相似,常被称为“双子”;但是它们确实在平面和外观细节部分有一些差异。


Early and personal life.

Born at Valandovo, Ivanov finished primary and secondary school in his hometown. He lived there until the age of 27, then moved to Skopje, which has since been his permanent residence.  Ivanov is married to Maja Ivanova. Together they have a son named Ivan.

Political and civil society activism.

Ivanov has been politically active since the Yugoslav era, when he pushed for political pluralism and market economy. Until 1990 he was an activist in the League of Socialist Youth of Yugoslavia and a member of the last presidency of the organisation, where he worked on reforming the political system and promoting political plurality and free market economy.  Ivanov is considered a leading expert on civil society, specialising in political management. He is the founder and honorary president of the Macedonian Political Science Association and one of the founding members of the Institute for Democracy Societas "Civilis", a leading analytical centre in North Macedonia.

Academic career.

His professional career began in 1988, when he became an editor at the Macedonian Radio and Television, the national broadcasting station. He later taught political theory and political philosophy at the Law Faculty of the University of Skopje. In 1999, he became a visiting professor for the Southeast European programme at the University of Athens in Greece.  A series of academic appointments followed, including at universities in Bologna and Sarajevo. Ss. Cyril and Methodius University of Skopje named him associate professor in 1992 and a full-time professor in 2008. The same year, he became president of the Council for Accreditation in Higher Education in Macedonia.

President of the Republic of Macedonia.

Campaign and election.

On 25 January 2009, the strongest party in the Macedonian parliament, VMRO-DPMNE, appointed Ivanov as the party's presidential candidate for the 2009 Macedonian presidential election. 1,016 party delegates voted for his candidacy at the party's convention. Although he was proposed as a candidate by VMRO-DPMNE, he is not a member of the party.  During his campaign, Ivanov announced that if he is going to be elected president, he would "insist on a meeting between the President of the Republic of Macedonia and the President of the Republic of Greece" and that one of his highest priorities is the resolution of the country's long-running name dispute with Greece.  In the first round of the 2009 Macedonian presidential election 343,374 (35.06%) citizens of The Republic Of Macedonia voted for Ivanov, the second being the candidate of the Social Democrats, Ljubomir Frčkoski, with 20.45% of the votes.  Ivanov won the second round of the presidential election with 453,616 votes; opposition candidate Ljubomir Frčkoski got 264,828 votes.  One day after his election, Ivanov reaffirmed his intention for a meeting to be realised between him and the president of Greece, Karolos Papoulias. He added that he will officialise his invitation just after taking office. After a meeting with the president of the Democratic Union for Integration, Ali Ahmeti, Ivanov announced that he will also include ethnic Albanian intellectuals in his future presidential cabinet.  On 16 April, Ivanov on a ceremony received the presidential certificate from the State Election Commission.

Inauguration.

Ivanov took office on 12 May 2009, thereby succeeding Branko Crvenkovski. After taking the oath he held his inauguration speech in the Macedonian parliament and made public his priorities - EU and NATO membership, economic recovery, inner stability, interethnic relations and good relations with the neighbouring countries, especially with Greece.  The swearing-in ceremony was attended by Crvenkovski, prime minister Nikola Gruevski, the first president of independent Republic of Macedonia Kiro Gligorov, military officials, leaders of the religious communities in Macedonia and foreign ambassadors in the county.  Also, four foreign statesmen were present — the president of Serbia Boris Tadić, the president of Montenegro Filip Vujanović, the president of Croatia Stjepan Mesić and the president of Albania Bamir Topi. Later that day Ivanov held bilateral talks with the four presidents.  The second inauguration of President Ivanov was held on 12 May 2014 in the Macedonian parliament The swearing-in ceremony was attended the prime minister Nikola Gruevski, military officials, leaders of the religious communities in Macedonia and foreign ambassadors in the county. The inauguration was boycotted by the Democratic Union for Integration the largest Albanian political party in the Republic of Macedonia and the Social Democratic Union of Macedonia the largest opposition party in Macedonia.

First term.

On the day Ivanov officially became president of his country, he sent a letter to the president of the United States Barack Obama in which he underlined The Republic Of Macedonia's aim to join NATO and EU and to find a "mutually acceptable solution" to the "name difference" with neighbouring Greece. He also thanked Obama for his words of support at the 2009 NATO Summit.  One day after the inauguration, Ivanov together with Prime Minister Gruevski travelled to Brussels to meet with European Union and NATO officials.  Ivanov claims to promote a Macedonian model of a multi-ethnic society and Pax Europaea, a united Europe living in peace and respecting the diversity and identity of the nations of Europe.

Second term.

Ivanov was re-elected as President of the Republic of Macedonia for a second term in April 2014.  In March 2016 Ivanov stated that the European Union had failed the Republic of Macedonia and other Balkan countries in the European migrant crisis.  On 12 April 2016 Ivanov halted judicial inquiries into officials involved in a wiretap scandal. Ivanov stated to have done so in the best interest of the country, and to end the political crisis. A move that the opposition called Ivanov's coup d'état and an effective disagreement to cooperate and find a common ground solution to the problem. His own party, the VMRO-DPMNE did not agree with his action. Opposition media called it a political manoeuvre to prevent further judicial inquiry by the special prosecutor Katica Janeva, proposed by the international community to normalise the political situation. Opposition leader Zoran Zaev subsequently called for protests. A demonstration occurred in Skopje on 13 April, with the presidential offices being attacked by rioters and several people detained.

Gjorge Ivanov (, ; born 2 May 1960) is a Macedonian politician, who served as President of North Macedonia from 2009 to 2019.

格奥尔基·伊万诺夫(,Gjorge Ivanov,1960年-5月2日),北马其顿前总统,代表马其顿内部革命组织民族统一民主党当选。


History.

TSW Pegasus was established on June 2008, and they had their first season in Hong Kong First Division League 2008–09 with a budget of about HKD$10,000,000.  On 21 December 2008, Pegasus won their first trophy, defeating Sun Hei in the 2008 Senior Shield Final.  In July 2012, the club was renamed as Sun Pegasus following introduction of a new sponsor.  After the 2014–15 season, Sun International Resources Limited withdrew their sponsorship. Their club was renamed Hong Kong Pegasus following a takeover by Canny Leung.

Colours and badge.

Pegasus's home colours are a red shirt with white shorts. Their away colours are a white shirt with black shorts. The current kits are designed by adidas. The team historically has played with an all yellow kit as their home colours, but after their name change to Hong Kong Pegasus, the club owners decided to make a change. It proved to be a largely unpopular decision with the club's fans.  The current Pegasus badge is a pegasus inside a yellow and red shield, which is representative of "creating miracles", "vigor", "vitality" and "creativeness" in Greek mythology.

Club equipment.

TSW Pegasus has a bus for team transportation which is sponsored by Fuso.  The team also rented an entire 48th floor of a block of Central Park Towers in Tin Shui Wai as accommodation for team members. Renovation work is already completed.

Stadium.

TSW Pegasus applied to the Hong Kong Football Association for the use of Yuen Long Stadium and Tin Shui Wai Sports Ground for its home matches. HKFA replied that it will grant the application provided the grass turf at the stadium is up to standard after its examination. Later, the HKFA accepted the application of having the Yuen Long Stadium as TSW Pegasus's home ground for the game against South China on 5 October 2008. The team's directors promised to make a fanfare at the stadium on the day.  HKFA chairman Leung Hung Tak later claimed that a total of three home games for TSW Pegasus will be played at Yuen Long Stadium in the 2008–09 season.  For the 2013–14 season, TSW Pegasus has moved its home ground from Yuen Long Stadium to Mong Kok Stadium.  From 2015 to 2018, the club used Hong Kong Stadium as their home ground.  By virtue of their third-place finish in the 2017–18 season, Pegasus exercised their right to use the Mong Kok Stadium for 2018–19.

Supporters.

Pegasus has a fanbase mainly based in Yuen Long and Tin Shui Wai as they are Pegasus' original home districts. The club has an official fanclub known as "Pegasus Base". The club's slogan is "Pegasus, our team".

Community contribution.

TSW Pegasus held a big recruitment event at Tin Shui Wai Sports Ground to recruit U-15 and U-19 team players on 3 August 2008. At the same time, the team also recruited a few team assistants in order to provide job opportunity for the local residents. It played a friendly game against South China in the afternoon and the teams drew 1–1, TSW Pegasus lost (3–5) on penalties.

Hong Kong Pegasus FC () are a Hong Kong professional football club based in Kwai Chung. Founded in 2008, the club currently competes in the Hong Kong Premier League.

香港飞马足球会(英文:Hong Kong Pegasus FC)简称香港飞马或飞马,是香港一间职业足球会。香港飞马的前身,是于2008年由元朗区的热心人士筹组的「天水围飞马」(TSW Pegasus)。


Background.

AOL website.

In 1996, 15-year-old Eric Harris created a private website on America Online (AOL). It was initially to host levels (WADs) Harris created for use in the first-person shooter video games "Doom" and "Doom II", as well as "Quake". On the site, Harris began a blog, which included jokes and his thoughts on his family, friends and school. It also detailed Harris sneaking out of the house to cause mischief and vandalism, such as lighting fireworks, with his friend Dylan Klebold and others.  Harris worked at a fireworks stand, and had received several fireworks as a result. The mascot of Columbine High School (CHS) is the Rebels, and they called the sneaking out "Rebel Missions". Harris and Klebold adopted the nicknames "Reb" and "Vodka", respectively. Beginning in early 1997, the blog postings began to show the first signs of Harris's anger against society.

Van break-in.

On January 30, 1998, Harris and Klebold were arrested for breaking into a van parked near Littleton and stealing tools and computer equipment. They would subsequently attend a joint court hearing, where they pled guilty to the felony theft. The judge sentenced them to a juvenile diversion program. As a result, both delinquents

Journals.

Harris and Klebold kept journals, which were released to the public in 2006. In the journals, the pair would eventually document their arsenal and plan of attack.  Shortly after the court hearing for the van break-in, Harris reverted his website back to just posting user-created levels of "Doom". He

Schoolwork.

Harris and Klebold also used their schoolwork to foreshadow the massacre. They both displayed themes of violence in their creative writing projects. Harris wrote a paper on school shootings, and a poem from the perspective of a bullet. Klebold wrote a short story

Tapes.

Harris and Klebold were both enrolled in video production classes and kept five videotapes that were recorded with school video equipment. Only two of these, "Hitmen for Hire" and Rampart Range, and part of a third have been released.  The remaining three tapes detail their plans and reasons for the massacre, including the ways they hid their weapons and deceived their parents. Most of these were shot in the Harris family basement, and are known as the Basement Tapes. Thirty minutes before the attack, they made a final video saying goodbye and apologizing to their friends and families.  In December 1999, before anybody else had seen them, "Time" magazine published an article on these tapes. The victims' family members threatened to sue Jeffco. As a result, select victim families and journalists were allowed to see them, and they were then kept from the public indefinitely for fear of inspiring future massacres. The tapes have since allegedly been destroyed. There are only transcripts

Weaponry.

Guns.

In the months prior to the attacks, Harris and Klebold acquired two 9 mm firearms and two 12-gauge shotguns. Harris had a Hi-Point 995 Carbine with thirteen 10-round magazines and a Savage-Springfield 67H pump-action shotgun. Klebold used a 9×19mm Intratec TEC-9 semi-automatic handgun with one 52-, one 32-, and one 28-round magazine and a Stevens 311D double-barreled shotgun. Harris's shotgun was sawed-off to around and Klebold shortened his shotgun's length to, a felony under the National Firearms Act.

Tanner Gun Show.

On November 22, 1998, their friend Robyn Anderson purchased the carbine rifle and the two shotguns for the pair at the Tanner Gun Show, as they were too young to legally purchase

Mark Manes and Phil Duran.

Harris and Klebold both held part-time jobs at a local Blackjack Pizza. Through Philip Duran, a coworker, Klebold bought a TEC-9 handgun from Mark Manes for $500 at another gun show on January 23. Manes, Manes' girlfriend, and Duran are all in the Rampart Range video.  After the massacre, Manes and Duran were both prosecuted. Each was charged with supplying a handgun to a minor and possession of a sawed-off shotgun. Manes and Duran were sentenced to a total of six years and four-and-a-half years in prison, respectively.

Explosives.

In addition to the firearms, the complex and highly planned attack involved several improvised explosive devices. Using instructions obtained via the Internet and the "Anarchist Cookbook", Harris and Klebold constructed a total of 99 bombs.  These included pipe bombs, carbon dioxide cartridges filled with gunpowder (called "crickets"), Molotov cocktails, propane tanks converted to bombs, car bombs, and diversionary bombs. For ignition, they used kitchen matches and model rocket igniters as well as timing devices built from clocks and batteries for the propane, car, and diversion bombs. During the massacre, they carried lighters as well as match strikers taped to their forearms to light the pipe bombs and crickets. They had 45 crickets, 8 of which detonated, and 9 Molotov cocktails, 2 of which functioned.  Harris also attempted to make napalm, and envisioned a kind of backpack and flamethrower. They both attempted to get another friend and coworker Chris Morris, who was a part of the Trench Coat Mafia, to keep the napalm at his house, but he refused. Harris also tried to recruit him to be a third shooter, but would play it off as a joke when rebuked.

Pipe bombs.

Harris's website contained directions on making pipe bombs, including use of shrapnel. Harris's parents once discovered one of his pipe bombs. Harris's journal logged the creation of 25 pipe bombs. A total of 35 were

Propane bombs.

They had 8 propane tanks used for bombs. The weekend before the shootings, Harris and Klebold bought two propane tanks and other supplies from a hardware store for a few

Car bombs.

Each car bomb was made from pipe bombs and two 20-pound propane tanks, with gas cans and bottles set throughout. 8 pipe bombs were used in Klebold's car, and 1 in Harris's.

Knives.

Harris and Klebold each carried two knives, which were never used during the massacre. Harris had

The massacre.

According to their journals and video tapes, it is believed by investigators that the pair intended to detonate their propane bombs in the cafeteria at the busiest lunch hour, killing hundreds of students. After this they would shoot survivors. They would also be able to stab or toss bombs. Eventually bombs set in their cars in the parking lot would also detonate, killing more students as well as possibly any police vehicles, ambulances, fire trucks, or reporters who had come to the school. However this failed to occur since the bombs in the cafeteria and cars failed to detonate.  Several official sources claim they planned to shoot the fleeing survivors from the parking lot, but moved to the staircase on the hill at the west side of the school when the bombs failed. Other sources claim the top of the staircase where the massacre began was their preferred spot to wait for the bombs to go off all along.

Planting the bombs.

On Tuesday morning, April 20, 1999, Harris and Klebold placed two duffel bags in the cafeteria. Each bag contained propane bombs, which were set to detonate at 11:17 a.m., during the "A" lunch shift.  No witness recalled seeing the duffel bags being added to the 400 or so backpacks that were already in the cafeteria. The security staff at CHS did not observe the bags being placed in the cafeteria; a custodian was replacing the school security videotape at around 11:14 a.m., which might have been the time that the duffel bags were dropped off. Some

11:19 a.m.: Shooting begins.

At 11:19 a.m., 17-year-old Rachel Scott and her friend Richard Castaldo were having lunch and sitting on the grass next to the west entrance of the school. Klebold threw a pipe bomb towards the parking lot; the bomb only partially detonated, causing it to give off smoke. Castaldo thought it was no more than a crude senior prank. Several students during the incident first thought that they were watching a prank.  A witness reported hearing "Go! Go!" before Klebold and Harris pulled their guns from beneath their trench coats and began shooting. Scott was killed instantly when she was hit four

11:22 a.m.: Police response.

At 11:22 a.m., a custodian called Deputy Neil Gardner, the assigned resource officer to Columbine, on the school radio, requesting assistance in the senior parking lot. The only paved route took him around the school to the east and south on Pierce Street, where at 11:23 a.m., he heard on his police radio that a female was down, and assumed she had been struck by a car. While exiting his patrol car in the Senior lot at 11:24 a.m., he heard another call on the school radio, "Neil, there's a shooter in the school".  Harris, at the west entrance, immediately turned and fired ten shots from his carbine at Gardner, who was sixty yards away.

11:29–11:36 a.m.: Library massacre.

As the shooting unfolded, pipe bombs were tossed in the hallways and down into the cafeteria. Patti Nielson in the library called 9-1-1, telling her story and urging students in the library to take cover beneath desks. According to transcripts, her call was received by a 9–1–1 operator at 11:25:18 a.m. At 11:29 a.m., the gunmen entered the library. Fifty-two students, two teachers and two librarians were inside.  Harris yelled "Get up!" When nobody responded, Harris fired his shotgun twice at a desk. Student Evan Todd had been standing near a pillar when the shooters entered the library and had just taken cover behind a copier. Todd was hit by wood splinters in the eye and lower back but was not seriously injured. He then hid behind the administrative counter once Harris and Klebold moved.  The shooters walked into the library, towards the two rows of computers. Disabled student Kyle Velasquez was sitting at the north row. Klebold fired his shotgun twice at Velasquez, fatally hitting him in the head and back. The shooters put down their ammunition-filled duffel bags at the south—or lower—row of computers and reloaded their weapons. They walked between the computer rows, toward the windows facing the outside staircase. They – especially Klebold, began shouting and speaking to all the students in the library.  Throughout the massacre in the library, they ordered everybody in the library to get up and said the library was going to explode. They stated how long they had been waiting for this, and seemed to be enjoying themselves, shouting things like "yahoo" after shooting. They repeatedly ordered the jocks to stand up. One of them said "Anybody with a

12:08 pm: Suicides.

After leaving the library, Harris and Klebold entered the science area, where they caused a fire in an empty storage closet. It was extinguished by a teacher who had hidden in an adjacent room. The gunmen then proceeded toward the south hallway, where they shot into an empty science room. At 11:44 a.m., they were captured on the school security cameras as they re-entered the cafeteria. The recording shows Harris kneeling on the landing and firing a single shot toward one of the propane bombs left

Crisis ends.

SWAT response.

By 12:00 p.m., SWAT teams were stationed outside the school, and ambulances started taking the wounded to local hospitals. A call for additional ammunition for police officers in case of a shootout came at 12:20 pm. Authorities reported pipe

Leawood Elementary.

Meanwhile, families of students and staff were asked to gather at nearby Leawood Elementary School to await information. All students, teachers, and school employees were taken

The boy in the window.

Patrick Ireland had regained and lost consciousness several times after being shot by Klebold. Paralyzed on his right side, he crawled to the library windows where, on live television, at 2:38 pm, he stretched out the window, intending to fall into the arms of two SWAT team members standing on the roof of an emergency vehicle, but instead falling directly

"1 bleeding to death".

At 2:15 pm students placed a sign in the window: "1 bleeding to death," in order to alert police and medical personnel of Dave Sanders' location in the science room. Police initially feared it was a ruse by the shooters. A shirt was also tied to the doorknob. At 2:30 p.m. this was spotted,

Suicide mission; estimated 25 dead.

Kreutz was finally evacuated at 3:22 p.m., along with Patti Nielson, Brian Anderson, and the three library staff who had hidden in the rooms adjacent to the library.

Bomb squad response.

Stone said that police officers were searching the bodies of the gunmen. They feared they had used their pipe bombs to booby-trap corpses, including their own. At 4:30 pm the school was declared safe. At 5:30 pm, additional officers were called in, as more explosives were found in the parking lot and on the roof. By 6:15 pm, officials had found a

Immediate aftermath.

On the morning of April 21, bomb squads combed the high school. By 8:30 am the official death toll of 15 was released. The earlier estimate was ten over the true death toll count, but close to the total count of wounded students. The total count of deaths was 12 students (14 including the shooters) and one teacher; 20 students and one teacher were injured as a result of the shootings. Three more victims were injured indirectly as they tried to escape the school. It was then the worst school shooting in U.S. history.  At 10:00 am, the bomb squad declared the building safe for officials to enter. By 11:30 am, a spokesman of the sheriff declared the investigation underway. Thirteen of the bodies were still inside the high school as investigators photographed the building.  At 2:30 pm, a press conference was held by Jeffco District Attorney David Thomas and Sheriff John Stone, at which they said that they suspected others had helped plan the shooting. Formal identification of the dead had not yet taken place, but families of the children thought to have been killed had been notified.  Throughout the late afternoon and early evening, the bodies were gradually removed from the school and taken to the Jeffco Coroner's Office to be identified and autopsied. By 5:00 pm, the names of many of the dead were known. An official statement was released, naming the 15 confirmed deaths and 27 injuries related to the massacre. On April 22, the cafeteria bombs were discovered.  In the days following the shootings, Rachel Scott's car and John Tomlin's truck became memorials, and impromptu memorials were held in Clement Park. On April 30, carpenter Greg Zanis erected 15 six feet tall wooden crosses to honor those who had died at the school. Daniel Rohrbough's father cut down the two meant for the gunmen. There were also fifteen trees planted, and he cut down two of those as well.

Search warrant press conference.

Also on April 30, high-ranking officials of Jeffco and the Jeffco Sheriff's Office met to decide if they should reveal that Michael Guerra had drafted an affidavit for a search warrant of Harris's residence more than a year before the shootings, based on his previous investigation of Harris's website and activities. Since the affidavit's contents lacked the necessary probable cause, they decided not to disclose this information at a press conference held on April 30, nor did they mention it in

Christian martyrdom.

In the wake of the shooting, victims Rachel Scott and Cassie Bernall came to be regarded as Christian martyrs by Evangelical Christians. Christian churches used the martyr narrative of Scott's and Bernall's deaths to promote themselves and recruit members.  Considerable media attention focused upon Bernall, who had been killed by Harris in the library and who Harris was reported to have asked, "Do you believe in God?" immediately prior to her murder. Bernall was reported to have responded "Yes" to this question before her murder.

We are Columbine.

Classes at Columbine were held at nearby Chatfield Senior High for the remaining three weeks of the

Additional related-deaths.

Several former students and teachers suffer from PTSD. Six months after the shootings, Anne Marie Hochhalter's mother killed herself. Greg Barnes, a student who witnessed Sanders

Rationale.

The shooting was planned as a terrorist attack that would cause "the most deaths in U.S. history", but the motive has never been ascertained with any degree of certainty. Soon after the massacre, it was thought Harris and Klebold targeted jocks, blacks, and Christians. Both sought to provide answers in the journals and videotapes, but investigators found them lacking. In a letter provided with the May 15 report on the Columbine attack, Sheriff John Stone and Undersheriff John A. Dunaway wrote they "cannot answer the most fundamental question—why?" On May 3, 1999, an issue of "Newsweek" was dedicated to the massacre, with the cover asking "Why?" in large print.

FBI's theory: Psychopath and depressive.

The FBI concluded that the killers were victims of mental illness, that Harris was a clinical psychopath, and Klebold was depressive. Dr. Dwayne Fuselier, the supervisor in charge of the Columbine investigation, would later remark: "I believe Eric went to the school to kill and didn't care if he died, while Dylan wanted to die and didn't care if others died as well."  In April 1998 (a year before the shooting), Harris wrote a letter of apology to the owner of the van as part of his diversion program. Around the same time, he derided him in his journal, stating that he believed himself to have the right to steal something if he wanted to. By far the most prevalent theme in Klebold's journals is his

Other factors.

The FBI's theory has been met with criticism. Critics cite the fact that Klebold, not Harris, was the first to mention a killing spree in his journal. They also cite evidence that Harris was depressed as well, such as his prescription for antidepressants mentioned below.

Bullying.

Early stories following the massacre charged that school administrators and teachers at Columbine had long condoned jocks bullying and this explained the motive. The link between bullying and school violence has attracted increasing attention since.  Accounts from various parents and school staffers reported bullying in the school. Reportedly, Harris and Klebold were regularly called "faggots". Klebold said on the Basement Tapes, "You've been giving us shit for years." And when talking to his father about jocks had stated, "They sure give Eric hell." Brown also noted Harris was born with mild chest indent. This made him reluctant to take his shirt off in gym class, and other students would laugh at him. Nathan Vanderau, a friend of Klebold, and Alisa Owen, who knew Harris, noted they were picked on. Vanderau recalled that a "cup of fecal matter" was thrown at them.  It has been alleged that Harris and Klebold were once both confronted by a group of students at CHS who sprayed them with ketchup while referring to them as "faggots" and "queers". Klebold told his mother it had been

Outcasts.

During and after the initial investigations, social cliques within high schools such as the Trench Coat Mafia were widely discussed. One perception formed was that Harris and Klebold were both outcasts who had been isolated from their classmates, prompting feelings of helplessness, insecurity, and depression, as well as a strong need for power and attention. Harris's last

Political terrorism.

Sociologist Ralph Larkin has theorized the massacre was to trigger a revolution of outcast students and the dispossessed; "as an overtly political act in the name of oppressed students victimized by their peers...The Columbine shootings redefined such acts not merely as revenge but as a means of protest of bullying, intimidation, social isolation, and public rituals of humiliation." One author argues Columbine was only increasingly linked to terrorism after the September 11 attacks.  On the Basement Tapes, Harris claimed they would "kick-start a revolution". Klebold wore a Soviet Union pin on his boots during the massacre.  The attack occurred on April 20 (Adolf Hitler's birthday), which led to media speculation that the attack was political. Some people, such as Robyn Anderson, stated that the pair were not obsessed with National

Medication.

Opponents of contemporary psychiatry like Peter Breggin claimed that the psychiatric medications prescribed to Harris may have exacerbated his aggressiveness. Toxicology reports confirmed that Harris had Luvox in his bloodstream at the time of the shootings. Klebold had no medications in his system.  Also as a part of diversion, Harris began therapy with a psychologist and a psychiatrist. Harris continued his scheduled meetings with his

Music.

Blame for the shootings was also directed at other metal or 'dark music' bands.

Film.

Parents of some of the victims filed several unsuccessful lawsuits against film companies, over films such as "The Basketball Diaries", which includes a dream sequence with a student shooting his classmates in a trench coat. In the Basement Tapes, they debate on whether or not Steven Spielberg or Quentin Tarantino are appropriate choices to direct films about the massacre. Their home videos also show inspiration taken from "Pulp Fiction". Both were fans of the film "Lost Highway"."Apocalypse Now" was found in Harris's VCR.

Video games.

Violent video games were also blamed. Parents of some of the victims filed several unsuccessful lawsuits against video game manufacturers. Jerald Block believes their immersion in a virtual world best explains the massacre. While Brooks Brown disagrees that video games caused the shooting, he agrees elements of their plan came from video games.  Harris and Klebold were both fans of shooter video games such as "Doom", "Quake", "Duke Nukem 3D" and "Postal". Harris wrote the massacre will "be like the LA riots, the Oklahoma bombing, WWII, Vietnam, "Duke" and "Doom" all mixed together." In his last journal entry, Harris wished to "Get a few extra frags on the scoreboard."

Perpetrators.

Eric Harris.

Eric David Harris (April 9, 1981 – April 20, 1999) was born in Wichita, Kansas. The Harris family relocated often, as Harris's father was a U.S. Air Force transport pilot. His mother was a homemaker. The family moved from Plattsburgh, New York, to Littleton,

Dylan Klebold.

Dylan Bennet Klebold (; September 11, 1981 – April 20, 1999) was born in Lakewood, Colorado. His parents were pacifists and attended a Lutheran church with their children. Both Dylan and his older brother attended confirmation classes in accordance with the Lutheran tradition. As had been the case with his older brother, Klebold was named after a renowned poet – in his case the playwright Dylan Thomas.  At the family home,

Legacy.

Following the Columbine shooting, schools across the United States instituted new security measures such as see-through backpacks, metal detectors, school uniforms, and security guards. Some schools implemented the numbering of school doors in order to improve public safety response. Several schools throughout the country resorted to requiring students to wear computer-generated IDs.  Schools also adopted a zero tolerance approach to possession of weapons and threatening behavior by students. Despite the effort, several social science experts feel the zero tolerance approach adopted in schools has been implemented too harshly, with unintended consequences creating other problems. Despite the safety measures that were implemented in the wake of the tragedy at Columbine, school shootings continued to take place in the United States at an alarming rate. Virginia Tech, Sandy Hook, and Stoneman Douglas were three subsequent school shootings that far eclipsed the terror that took place at Columbine.  Some schools renewed existing anti-bullying policies. Rachel's Challenge was started by Rachel Scott's parents, and lectures schools about bullying and suicide.

Police tactics.

Police departments reassessed their tactics and now train for Columbine-like situations after criticism over the slow response and progress of the SWAT teams during the shooting. Sheriff Stone did not seek reelection.  Police followed a traditional tactic at Columbine: surround the building, set up a perimeter, and contain the damage. That approach has been replaced by a tactic known as the Immediate Action Rapid Deployment tactic. This tactic

Lawsuits.

After the massacre, many survivors and relatives of deceased victims filed lawsuits. Under Colorado state law at the time, the maximum a family could receive in a lawsuit against a government agency was $600,000. Most cases against the Jeffco police department and school district were dismissed by the federal court on the grounds of government immunity. The case against the sheriff's office regarding the death of Dave Sanders was not dismissed due to the police preventing paramedics from going to his aid for hours after they knew the gunmen were dead. The case was

Memorials.

Many impromptu memorials were created after the massacre, including victims Rachel Scott's car and John Tomlin's truck.  In 2000, youth advocate Melissa Helmbrecht organized a remembrance event in Denver featuring two surviving students, called "A Call to Hope." The library where most of the massacre took place was removed and replaced with an atrium. In 2001, a new library, the HOPE memorial library, was built next to the west entrance.  On February 26, 2004, thousands of pieces of evidence from the massacre were put on display at the Jeffco fairgrounds in Golden.  A permanent

Gun control.

The shooting resulted in calls for more gun control measures. The gun show loophole and background checks became a focus of a national debate. It was the deadliest mass shooting during the era of the Federal Assault Weapons Ban. Victim Daniel Mauser's father Tom Mauser has become a gun control advocate.  In 2000, federal and state legislation was introduced that would require safety locks on firearms as well as

Popular culture.

"Columbine" has since become a euphemism for a school shooting, rather like "going postal" is for workplace violence. A video game called "Super Columbine Massacre RPG!" was based on the massacre.  The 2016 biographical film "I'm Not Ashamed", based on the journals of Rachel Scott, includes glimpses of Harris's and Klebold's lives and interactions with other students at CHS. The 1999 black comedy, "Duck! The Carbine High Massacre" is inspired by the Columbine massacre. The 2003 Gus Van Sant film "Elephant" depicts a fictional school shooting, but is based in part on the Columbine massacre. The 2003 Ben Coccio film "Zero Day" was also based on the massacre.  The first documentary on the massacre may have been the TLC documentary "Lost Boys" in 2000. The 2002 Michael Moore documentary film "Bowling for Columbine" won several awards. Also in 2002, A&E made "Columbine: Understanding Why".  In 2004, the shooting was dramatized in the documentary "Zero

Copycats.

The Columbine shootings influenced subsequent school shootings, with several such plots mentioning it. Fear of copycats has sometimes led to the closing of entire school districts. Since Columbine, over 74 copycat cases have been reported, 21 of which resulted in attacks, while the rest were thwarted by law enforcement. In many of them, the perpetrators cited Harris and Klebold as heroes or martyrs. Harris and Klebold have become what the "Napa Valley Register" have called "cultural icons" for troubled youth. According to psychiatrist E. Fuller Torrey of the Treatment Advocacy Center, a legacy of the Columbine shootings is its "allure to disaffected youth."  Ralph Larkin examined twelve major school shootings in the US in the following eight years and found that in eight of those, "the shooters made explicit reference to Harris and Klebold." Larkin wrote that the Columbine massacre established a "script" for shootings. "Numerous post-Columbine rampage shooters referred directly to Columbine as their inspiration; others attempted to supersede the Columbine shootings in body count."  A 2015 investigation by CNN identified "more than 40 people...charged with Columbine-style plots." A 2014 investigation by ABC News identified "at least 17 attacks and another 36 alleged plots or serious threats against schools since the assault on Columbine High School that can be tied to the 1999 massacre." Ties identified by ABC News included online research by the perpetrators into the Columbine shooting, clipping news coverage and images of Columbine, explicit statements of admiration of Harris and Klebold, such as writings in journals and on social media, in video posts, and in police interviews, timing planned to an anniversary of Columbine, plans to exceed the Columbine victim counts, and other ties.  In 2015, journalist Malcolm Gladwell writing in "The New Yorker" magazine proposed a threshold model of school shootings in which Harris and Klebold were the triggering actors in "a slow-motion, ever-evolving riot, in which each new participant's action makes sense in reaction to and in combination with those who came before."  The first copycat may have been the W. R. Myers High School shooting, just eight days after Columbine, when a 14-year-old Canadian student went into his school

The Columbine High School massacre was a school shooting and attempted bombing that occurred on April 20, 1999, at Columbine High School in Columbine, Colorado, United States. The perpetrators, twelfth grade (senior) students Eric Harris and Dylan Klebold, murdered 12 students and one teacher. Ten students were killed in the school library, where the pair subsequently committed suicide. Twenty-one additional people were injured by gunshots, and gunfire was also exchanged with the police. Another three people were injured trying to escape the school. At the time, it was the deadliest school shooting in U.S. history. The crime has inspired several copycats (see Columbine effect) and "Columbine" has become a byword for mass shootings.

科伦拜校园事件是1999年4月20日于美国科罗拉多州杰佛逊郡哥伦拜恩高中发生的校园枪击事件。两名青少年学生—埃里克·哈里斯和迪伦·克莱伯德配备枪械和爆炸物进入校园,枪杀了12名学生和1名教师,造成其他24人受伤,两人随即自杀身亡。这起事件被视为美国历史上最血腥校园枪击事件。


曼苏尔·本·扎耶德·阿勒纳哈扬

Early life and education.

Mansour was born in the Abu Dhabi emirate on 20 November 1970, the fifth son of the Emir of Abu Dhabi Sheikh Zayed bin Sultan Al Nahyan. His mother is Sheikha Fatima bint Mubarak Al Ketbi and he has five full-brothers: Crown Prince Mohammed, Hamdan, Hazza, Tahnoun, and Abdullah. They are known as Bani Fatima or sons of Fatima.  Mansour attended Santa Barbara Community College as an English student in 1989. He is a graduate of United Arab Emirates University where he received a bachelor's degree in international affairs in 1993.

Political career.

In 1997, Mansour bin Zayed was appointed chairman of the presidential office, which his father Zayed II is the first and by-then president of UAE. After the death of his father, he was appointed by his eldest half brother, Khalifa II, as first minister of presidential affairs of the United Arab Emirates, which is the merger of the presidential office and presidential court. He also served in a number of positions in Abu Dhabi to support his brother, Crown Prince Mohammed bin Zayed Al Nahyan.  He was appointed chairman of the ministerial council for services, which is considered a ministerial entity attached to the Cabinet, comprising a number of ministers heading the services departments. Since 2000 he chaired National Center for Documentation and Research. In 2004 reshuffle, he became minister for presidential affairs. In 2005, he became the deputy chairman of the Abu Dhabi education council (ADEC), chairman of the Emirates Foundation, Abu Dhabi Food Control Authority, and Abu Dhabi Fund for Development. In 2006, he was named the chairman of the Abu Dhabi Judicial Department. In 2007, he was appointed chairman of Khalifa bin Zayed Charity Foundation.  Mansour served as the chairman of First Gulf Bank until 2006, and as a member of the board of trustees of the Zayed charitable and humanitarian foundation. Mansour has established scholarship programs for U.A.E students to study abroad. He is also chairman of the Emirates horse racing authority (EHRA). On 11 May 2009, he was appointed deputy prime minister, retaining his cabinet post of minister of presidential affairs.

Business portfolio.

Mansour heads IPIC, which owns 71% of Aabar Investments and is used as an investment vehicle. After the 1Malaysia Development Berhad (1MDB) scandal was highlighted and Khadem al-Qubaisi, who was managing IPIC, was arrested in 2016, IPIC was folded into Aabar Investments. Qubaisi blamed Mansour and the UAE authorities for using him as a scapegoat in the affair. Mansour is the chairman of the Abu Dhabi Judicial Department and Qubaisi is being held in prison without charge.  In 2005, he was appointed as a member of the Supreme Petroleum Council. In the same year he chaired the board of directors of IPIC and became the board member of the Abu Dhabi Investment Authority (ADIA). In 2007, he was appointed chairman of the Emirates Investment Authority, the sovereign wealth fund of UAE.  Mansour has a 32% stake in Virgin Galactic after investing $280m in the project through Aabar in July 2009. Aabar also has a 9.1% stake in Daimler after purchasing the stake for $2.7 billion in March 2009 and it was reported that Aabar wishes to increase its stake to 15% in August 2010. He owns the Abu Dhabi Media Investment Corporation (ADMIC) which partnered with British Sky Broadcasting to establish Sky News Arabia – a new Arabic-language news channel headquartered in the Emirate of Abu Dhabi. ADMIC also owns the English-language newspaper "The National".

Sport.

Mansour is an accomplished horse rider and has won a number of endurance racing tournaments held in the Middle East, and is chairman of the Emirates horse racing authority. He is a strong supporter of Arabian horse racing and the patron of the annual Zayed International Half Marathon competition in Abu Dhabi.  He is the chairman of the Al Jazira sports company and was a leading figure in the Emirate of Abu Dhabi’s successful bid to host in UAE the FIFA Club World Cup in 2009 and 2010. The company owns Al Jazira Club, which plays football, volleyball, handball and basketball. The football club won the President’s Cup in 2010-2011 and 2011-2012.  In September 2008, Sheikh Mansour acquired Manchester City football club from former Thai prime minister Thaksin Shinawatra. By September 23, 2008, the Abu Dhabi United Group, backed by Mansour, completed their takeover negotiations and the ownership was transferred to them. He also owns the City Football Group, which was founded in 2014 and consists of Manchester City FC, Melbourne City FC and New York City FC and others. City's ownership was deemed as United Arab Emirates’ attempt to “sportswash” its image and as an instrument of foreign policy by several human rights groups, including Amnesty International and Human Rights Watch (HRW).  In 2014, UEFA found that Mansour’s team breached the Financial Fair Play (FFP) rules. The club was fined £49 million, while £32 million were suspended. Moreover, City’s Champions League squad for 2014-15 was also reduced to only 21 players. In 2018, the club came under fresh allegations of breach. A German newspaper Der Spiegel wrote a four-chapter story highlighting that Mansour neglected FFP rules and bulked up ‘sponsorship’ deals with his own money. The Emirati provided £59.5 million of a £67.5 million for an agreement signed with Etihad Airways. The report also revealed a £15 million annual deal with an investment firm Aabar, through an internal email sent by executive Simon Pearce in April 2010. The club refused to comment and called it an attempt to damage their reputation was “organised and clear”. City stated that the emails and documents have been obtained illegally. A book called "Can We Have Our Football Back? How the Premier League Is Ruining Football And What We Can Do About It”, by John Nicholson reportedly claims that Premier League has corrupted football by turning the sport into a money making business. The alleged'sportswash' campaign run by Mansour's Manchester City is among the several scandals mentioned by John in his book, demanding scrutiny towards them. In May 2019, UEFA opened investigation into Manchester City on allegations that the club misled European soccer’s financial regulators. However, the club still reserved right to appeal to the Court of Arbitration for Sport. In November 2019, the Court of Arbitration for Sport ruled against Manchester City's attempt to block investigation into breach of financial fair play rules. As per the records published by Court of Arbitration, Manchester City in its appeal to block investigation for FFP claimed damages from UEFA. The club claimed that the alleged leaks by Der Spigel were "unlawful" in regards to possible inquiry. However, Yves Leterme dismissed the claims calling them "groundless" and "unacceptable in tone" In February 2020, Manchester City were banned from UEFA Champions League for two seasons after they were found guilty of violating the financial fair play rule.UEFA in its statement said: "Manchester City Football Club committed serious breaches of the UEFA club licensing and financial fair play regulations." The adjudicatory chamber also informed that the club overstated its sponsorship revenue and used biased calculating methods for the financial accounts submitted between 2012 to 2016. The club responding to the verdict said that it would now approach Court of Arbitration for Sport and initiate proceedings as soon as possible.

Personal life.

Mansour married Sheikha Alia bint Mohammed bin Butti Al Hamed in the mid-1990s. Alia is the sister of Abdulla Bin Mohammed Bin Butti Al Hamed. They have one son, Zayed.  In 2005, Mansour married Manal bint Mohammed bin Rashid Al Maktoum. She is the daughter of Mohammed bin Rashid Al Maktoum ruler of Dubai. They have two daughters and three sons: Fatima (2006), Mohammed (2007), Hamdan (2011), Latifa (2014) and Rashid (2017)  Mansour is the owner of the yacht Topaz.

Mansour bin Zayed bin Sultan bin Zayed bin Khalifa Al Nahyan (born 20 November 1970), often referred to as Sheikh Mansour, is an Emirati politician who is the deputy prime minister of the United Arab Emirates, minister of presidential affairs and member of the royal family of Abu Dhabi. He is the half brother of the current President of UAE, Khalifa bin Zayed Al Nahyan.

谢赫曼苏尔‧本‧扎耶德‧阿勒纳哈扬(,Mansour bin Zayed bin Sultan Al Nahyan,1970年-11月20日),阿联酋副总理和阿布扎比酋长国王室成员。他是阿联酋国父扎耶德·本·苏尔坦·阿勒纳哈扬的儿子,同胞兄弟包括王储穆罕默德。


Biography.

Vetemaa was born in Tallinn to the family of an architect. He graduated from Tallinn Polytechnic Institute in 1959 with a degree in chemical engineering. His choice of the subject was influenced by his grandfather, a pioneer photographer and radio-engineer, who started photography in 19th century and experimented with radio-transmitting two years after Alexander Popov.  Without working out the required three years Vetemaa abandoned his engineering career and entered Tallinn Conservatoire that he graduated from in 1965. Despite being a very successful student of music Vetemaa decided that he is not as strong as his classmates: now famous Arvo Pärt and Jaan Rääts. Vetemaa abandoned music and returned to writing poetry.  First publications of Vetemaa's poetry were in 1958. He published books of poetry "Critical Age" ( ) in 1962 and "Game of snowballs" () in 1966. He became a notable figure among the young poets of Estonia, but his ironic and rational intellect forces to switch into prose.  In 1964 he finished and in 1966 published his arguably most-famous novel "Monument". The novel already does something that is unusual in the context of Estonian literature: the narrator is a negative character. In this way Vetemaa makes his readers enter the mind of a character for whom they feel no empathy. The narrator, a young successful sculptor kandidat of architecture Sven Voore, returns from Moscow to Tallinn to work on a memorial to fallen Soviet soldiers. He is supposed to decorate the pedestal for the work of a young talented sculptor Ain Saarema, but the problem is that the monument eventually designed by Ain does not need any pedestals: it shows only arms that the dead soldiers rise from their graves through the ground. The narrator's intrigues eventually lead to the monument eventually finished by a Stalinist Magnus Tee, the narrator getting the job of the pedestal, promotion in the Estonian art unions and the wife of Ain Sarema. The resulting monument is done in the traditions of the socialist realism but has ghostly long arms (inherited from the project of Ain).  The novel was originally forbidden to be published but Vetemaa happened to meet the censor. After a few days of heavy drinking with Vetemaa, the censor found courage to allow the novel for publications. The novel was printed at the climax of the Khrushchev Thaw and was well received. Vetemaa won the USSR Writer's Union prize for the best novel. In 1978 the novel was adapted as a play directed by Valery Fokin in Moscow Sovremennik Theater. It is consider to be the best theater work of Konstantin Raikin.  After "Monument" Vetemaa published other "small novels": "Tiredness" (Усталость) (1967), "Väike reekviem suupillile" (written in 1967, printed in 1968), "Munad hiina moodi" (English: "Chinese Eggs") (written – 1967–1969, printed – 1972). All together Vetemaa wrote ten "short novels"  Vetemaa continues to work as a playwright. His play "Õhtusöök viiele" ("Dinner for Five"), first performed in 1972, and the comedy "Püha Susanna ehk Meistrite kool" ("Saint Susanna or the School of Masters"), first performed in 1974, demonstrate Vetemaa's sharp eye and witty lines; texts without which Estonian theatre history would not be complete.  In 1983 Vetemaa prepared his most famous text compilation "Eesti näkiliste välimäärja" ("The Reference Book of Estonian Mermaids"), which mixes frivolity with popular science. He also wrote a lot of variations on the themes of Estonian epic poetry.  Speaking about the controversy caused by relocation of the Bronze Soldier of Tallinn, Vetemma supported the idea of erecting a monument to Boris Yeltsin on the vacant place. But he would prefer to use that site for a monument to Lennart Meri, the first Estonian president after the dissolution of the Soviet Union

Enn Vetemaa (June 20, 1936March 28, 2017) was an Estonian writer sometimes referred to as a "forgotten classic", as well as "the unofficial master of the Estonian Modernist short novel".

恩·韦捷马阿 (1936年-6月20日-2017年-3月28日)爱沙尼亚小说家,诗人,作品被称为“遗忘的经典”韦捷马阿被认为是爱沙尼亚现代主义短篇小说的非官方大师。


Early life and education.

Cushing was born in Scituate, Massachusetts Bay, on March 1, 1732. The Cushing family had a long history in the area, settling Hingham in 1638. Cushing's father John Cushing (1695–1778) was a provincial magistrate who in 1747 became an associate justice of the Superior Court of Judicature, the province's high court. William Cushing's grandfather John Cushing (1662–1737/38) was also a superior court judge and member of the governor's council.  Cushing's mother, Mary Cotton Cushing, was a daughter of Josiah Cotton (1679/80–1756). They were descended from Rev. John Cotton, the great 17th century Puritan theologian. Josiah Cotton and Richard Fitzgerald, a teacher at a local Latin school, were responsible for young Cushing's early education.  Cushing graduated from Harvard College in 1751 and became a member of the bar of Boston in 1755. After briefly practicing law in Scituate, he moved to Pownalborough (present-day Dresden, Maine, then part of Massachusetts), and became the first practicing attorney in the province's eastern district (as Maine was then known). In 1762 he was called to become a barrister, again the first in Maine. He practiced law until 1772, when he was appointed by Governor Thomas Hutchinson to replace his father (who had resigned) on the Superior Court bench.

Career.

Not long after his tenure on the Massachusetts bench began, a controversy arose over revelations that court judges were to be paid by crown funds from London rather than by an appropriation of the provincial assembly. Cushing did not express any opinion on the matter, but declined the crown payment in preference to a provincial appropriation.  After the American Revolutionary War broke out in April 1775, the Massachusetts Provincial Congress (which exercised "de facto" control over the province outside besieged Boston), sought to reorganize the courts to remove the trappings of British sovereignty. Consequently, it essentially dissolved the Superior Court and reformed it in November 1775. Of all its justices, Cushing was the only one retained.  The congress offered the seat of Chief Justice first to John Adams, but he never sat, and resigned the post in 1776. The provincial congress appointed Cushing to be the court's first sitting Chief Justice in 1777. He was a charter member of the American Academy of Arts and Sciences (1780). He would sit as Massachusetts Chief Justice until 1789, during which period the court ruled in 1783 that slavery was irreconcilable with the new state constitution, and it was ended in the state.

Massachusetts chief justice.

In 1783, Cushing presided over a series of cases involving Quock Walker, a slave who filed a freedom suit based on the language of the new state constitution. In "Commonwealth v. Jennison", Cushing stated the following principles, in his charge to the jury:  This was taken to mean that slavery was incompatible with the state constitution ratified in 1779, and that slavery was therefore ended in the state. The case relied on a 1781 freedom suit brought by slave Elizabeth Freeman (Mum Bett), also known as Mum Bett, on the same grounds; a Massachusetts county court ruled in her favor in 1781.  During Shays' Rebellion (1786–87), Cushing ensured that court sessions continued, despite the aggressive protests of the armed rebels, and later presided over their trials. A year later, in 1788, he served as vice president of the Massachusetts convention, which narrowly ratified the United States Constitution.

U.S. Supreme Court.

On September 24, 1789, President George Washington nominated Cushing for one of the five associate justice positions on the newly established Supreme Court. His appointment (along with those of: John Blair Jr.; Robert H. Harrison; John Rutledge; and James Wilson; plus that of John Jay for Chief Justice) was confirmed by the Senate two days later. Cushing's service on the Court officially began February 2, 1790, when he took the Judicial oath. He generally held a nationalist view typically in line with the views of the Federalist Party, and often disagreed with Thomas Jefferson's Democratic-Republicans. His two most important decisions were probably "Chisholm v. Georgia" and "Ware v. Hylton", which held that treaties made under the Constitution supersede state law. Though he served on the Court for two decades, only 19 of his decisions appear in the "United States Reports".  Cushing administered the oath of office at Washington's second inauguration on March 4, 1793. This was the first inauguration to take place in Philadelphia (then the nation's capital).  When Chief Justice John Jay resigned from the Court in June 1795, during a long Senate recess, Washington appointed John Rutledge as the new chief justice by a recess appointment. On December 15, 1795, during the Senate's next session, it rejected Rutledge's nomination. Washington subsequently nominated Cushing on January 26, 1796; the Senate confirmed the nomination the following day.  Cushing received his commission on January 27, but returned it to Washington on February 2, declining appointment. An error in the rough minutes of the Court on February 3 and 4, 1796, lists Cushing as Chief Justice, although this entry was later crossed out. This error can be explained by the text of the Judiciary Act of 1789, which allowed for the Court to hear cases with a quorum of only four justices; that is, the Chief Justice need not always be present for the Court to conduct business. As Cushing was the most senior associate justice present on those dates, he would have been expected to serve as the presiding justice, directing the Court's business.  Washington then nominated Oliver Ellsworth to be chief justice, transmitting the nomination to the Senate in a March 3 message stating that Ellsworth would replace "William Cushing, resigned." Subsequent histories of the Court have not counted Cushing as chief justice, but instead report that he declined the appointment. Had Cushing accepted promotion to chief justice and then resigned, he would have had to leave the Court entirely; accepting the appointment would have implicitly required Cushing to resign his place as associate justice. That he continued on the Court as an Associate Justice for years afterward lends weight to the assertion that Cushing declined promotion. Additionally, Cushing's February 2 letter explicitly stated his return of the commission for chief justice, and his desire to retain his seat as Associate Justice.

Later life and death.

In 1810, Cushing died in his hometown of Scituate, Massachusetts. He is buried in a small cemetery there which is also a state park.

William Cushing (March 1, 1732 – September 13, 1810) was one of the original five associate justices of the United States Supreme Court; confirmed by the United States Senate on September 26, 1789, he served until his death. His Supreme Court tenure of 20 years and 11 months was the longest among the Court's inaugural members. In January 1796, he was nominated by President George Washington to become the Court's Chief Justice; though confirmed, he declined the appointment. He was the last judge in the United States to wear a full wig (Court dress).

威廉·库欣(英语:William Cushing;1732年-3月1日-1810年-9月13日)或译为威廉·顾盛,马萨诸塞州人,1789-1810年担任美国最高法院大法官, 为华盛顿总统任命的美国最早六位大法官之一,也是华盛顿任命的所有大法官中任期最长的一位,参与了著名的奇泽姆诉乔治亚州案审判。