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char = ;code = 32 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = f;code = 102 char = l;code = 108 char = a;code = 97 char = v;code = 118 char = o;code = 111 char = n;code = 110 char = o;code = 111 char = i;code = 105 char = d;code = 100 char = ;code = 32 char = q;code = 113 char = u;code = 117 char = e;code = 101 char = r;code = 114 char = c;code = 99 char = e;code = 101 char = t;code = 116 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = c;code = 99 char = a;code = 97 char = u;code = 117 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = i;code = 105 char = t;code = 116 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = w;code = 119 char = n;code = 110 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = t;code = 116 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = r;code = 114 char = c;code = 99 char = i;code = 105 char = n;code = 110 char = o;code = 111 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = e;code = 101 char = f;code = 102 char = f;code = 102 char = e;code = 101 char = c;code = 99 char = t;code = 116 char = .;code = 46 char = ;code = 32 char = T;code = 84 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = l;code = 108 char = e;code = 101 char = x;code = 120 char = ;code = 32 char = [;code = 91 char = V;code = 86 char = O;code = 79 char = (;code = 40 char = Q;code = 81 char = u;code = 117 char = e;code = 101 char = r;code = 114 char = );code = 41 char = (;code = 40 char = 2;code = 50 char = );code = 41 char = E;code = 69 char = t;code = 116 char = O;code = 79 char = H;code = 72 char = ];code = 93 char = (;code = 40 char = ;code = 32 char = n;code = 110 char = ;code = 32 char = );code = 41 char = ;code = 32 char = (;code = 40 char = Q;code = 81 char = u;code = 117 char = e;code = 101 char = r;code = 114 char = V;code = 86 char = O;code = 79 char = );code = 41 char = ;code = 32 char = h;code = 104 char = a;code = 97 char = s;code = 115 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = e;code = 101 char = n;code = 110 char = ;code = 32 char = s;code = 115 char = y;code = 121 char = n;code = 110 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = s;code = 115 char = i;code = 105 char = z;code = 122 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = c;code = 99 char = h;code = 104 char = a;code = 97 char = r;code = 114 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = e;code = 101 char = r;code = 114 char = i;code = 105 char = z;code = 122 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = b;code = 98 char = y;code = 121 char = ;code = 32 char = m;code = 109 char = e;code = 101 char = a;code = 97 char = n;code = 110 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = d;code = 100 char = i;code = 105 char = f;code = 102 char = f;code = 102 char = e;code = 101 char = r;code = 114 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = s;code = 115 char = p;code = 112 char = e;code = 101 char = c;code = 99 char = t;code = 116 char = r;code = 114 char = o;code = 111 char = s;code = 115 char = c;code = 99 char = o;code = 111 char = p;code = 112 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = t;code = 116 char = e;code = 101 char = c;code = 99 char = h;code = 104 char = n;code = 110 char = i;code = 105 char = q;code = 113 char = u;code = 117 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = (;code = 40 char = U;code = 85 char = V;code = 86 char = -;code = 45 char = v;code = 118 char = i;code = 105 char = s;code = 115 char = ,;code = 44 char = ;code = 32 char = F;code = 70 char = o;code = 111 char = u;code = 117 char = r;code = 114 char = i;code = 105 char = e;code = 101 char = r;code = 114 char = ;code = 32 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = n;code = 110 char = s;code = 115 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = ;code = 32 char = I;code = 73 char = R;code = 82 char = ,;code = 44 char = ;code = 32 char = e;code = 101 char = l;code = 108 char = e;code = 101 char = c;code = 99 char = t;code = 116 char = r;code = 114 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = p;code = 112 char = a;code = 97 char = r;code = 114 char = a;code = 97 char = m;code = 109 char = a;code = 97 char = g;code = 103 char = n;code = 110 char = e;code = 101 char = t;code = 116 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = s;code = 115 char = o;code = 111 char = n;code = 110 char = a;code = 97 char = n;code = 110 char = c;code = 99 char = e;code = 101 char = );code = 41 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = i;code = 105 char = t;code = 116 char = s;code = 115 char = ;code = 32 char = m;code = 109 char = a;code = 97 char = g;code = 103 char = n;code = 110 char = e;code = 101 char = t;code = 116 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = s;code = 115 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = i;code = 105 char = l;code = 108 char = i;code = 105 char = t;code = 116 char = y;code = 121 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = p;code = 112 char = e;code = 101 char = r;code = 114 char = t;code = 116 char = i;code = 105 char = e;code = 101 char = s;code = 115 char = .;code = 46 char = ;code = 32 char = T;code = 84 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = h;code = 104 char = i;code = 105 char = b;code = 98 char = i;code = 105 char = t;code = 116 char = o;code = 111 char = r;code = 114 char = y;code = 121 char = ;code = 32 char = e;code = 101 char = f;code = 102 char = f;code = 102 char = e;code = 101 char = c;code = 99 char = t;code = 116 char = ;code = 32 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = b;code = 98 char = o;code = 111 char = v;code = 118 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = l;code = 108 char = k;code = 107 char = a;code = 97 char = l;code = 108 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = p;code = 112 char = h;code = 104 char = o;code = 111 char = s;code = 115 char = p;code = 112 char = h;code = 104 char = a;code = 97 char = t;code = 116 char = a;code = 97 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = (;code = 40 char = A;code = 65 char = L;code = 76 char = P;code = 80 char = );code = 41 char = ;code = 32 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = i;code = 105 char = t;code = 116 char = y;code = 121 char = ;code = 32 char = h;code = 104 char = a;code = 97 char = s;code = 115 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = e;code = 101 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = f;code = 102 char = r;code = 114 char = e;code = 101 char = e;code = 101 char = ;code = 32 char = l;code = 108 char = i;code = 105 char = g;code = 103 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ,;code = 44 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = l;code = 108 char = e;code = 101 char = x;code = 120 char = ;code = 32 char = a;code = 97 char = s;code = 115 char = ;code = 32 char = w;code = 119 char = e;code = 101 char = l;code = 108 char = l;code = 108 char = ;code = 32 char = a;code = 97 char = s;code = 115 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = v;code = 118 char = a;code = 97 char = n;code = 110 char = a;code = 97 char = d;code = 100 char = y;code = 121 char = l;code = 108 char = (;code = 40 char = I;code = 73 char = V;code = 86 char = );code = 41 char = ;code = 32 char = (;code = 40 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = a;code = 97 char = r;code = 114 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = e;code = 101 char = ;code = 32 char = p;code = 112 char = u;code = 117 char = r;code = 114 char = p;code = 112 char = o;code = 111 char = s;code = 115 char = e;code = 101 char = s;code = 115 char = );code = 41 char = .;code = 46 char = ;code = 32 char = T;code = 84 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = b;code = 98 char = i;code = 105 char = o;code = 111 char = l;code = 108 char = o;code = 111 char = g;code = 103 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = i;code = 105 char = t;code = 116 char = y;code = 121 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = l;code = 108 char = e;code = 101 char = x;code = 120 char = ;code = 32 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = l;code = 108 char = i;code = 105 char = f;code = 102 char = e;code = 101 char = r;code = 114 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = w;code = 119 char = o;code = 111 char = ;code = 32 char = o;code = 111 char = s;code = 115 char = t;code = 116 char = e;code = 101 char = o;code = 111 char = b;code = 98 char = l;code = 108 char = a;code = 97 char = s;code = 115 char = t;code = 116 char = -;code = 45 char = l;code = 108 char = i;code = 105 char = k;code = 107 char = e;code = 101 char = ;code = 32 char = c;code = 99 char = e;code = 101 char = l;code = 108 char = l;code = 108 char = s;code = 115 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = c;code = 99 char = u;code = 117 char = l;code = 108 char = t;code = 116 char = u;code = 117 char = r;code = 114 char = e;code = 101 char = ,;code = 44 char = ;code = 32 char = a;code = 97 char = ;code = 32 char = n;code = 110 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = o;code = 111 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = (;code = 40 char = M;code = 77 char = C;code = 67 char = 3;code = 51 char = T;code = 84 char = 3;code = 51 char = E;code = 69 char = 1;code = 49 char = );code = 41 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = a;code = 97 char = ;code = 32 char = t;code = 116 char = u;code = 117 char = m;code = 109 char = o;code = 111 char = r;code = 114 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = o;code = 111 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = (;code = 40 char = U;code = 85 char = M;code = 77 char = R;code = 82 char = 1;code = 49 char = 0;code = 48 char = 6;code = 54 char = );code = 41 char = ,;code = 44 char = ;code = 32 char = h;code = 104 char = a;code = 97 char = s;code = 115 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = e;code = 101 char = n;code = 110 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = a;code = 97 char = r;code = 114 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = w;code = 119 char = i;code = 105 char = t;code = 116 char = h;code = 104 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = v;code = 118 char = a;code = 97 char = n;code = 110 char = a;code = 97 char = d;code = 100 char = y;code = 121 char = l;code = 108 char = (;code = 40 char = I;code = 73 char = V;code = 86 char = );code = 41 char = ;code = 32 char = c;code = 99 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = q;code = 113 char = u;code = 117 char = e;code = 101 char = r;code = 114 char = c;code = 99 char = e;code = 101 char = t;code = 116 char = i;code = 105 char = n;code = 110 char = .;code = 46 char = ;code = 32 char = T;code = 84 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = d;code = 100 char = i;code = 105 char = f;code = 102 char = f;code = 102 char = e;code = 101 char = r;code = 114 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = i;code = 105 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = s;code = 115 char = t;code = 116 char = e;code = 101 char = o;code = 111 char = b;code = 98 char = l;code = 108 char = a;code = 97 char = s;code = 115 char = t;code = 116 char = ;code = 32 char = m;code = 109 char = a;code = 97 char = r;code = 114 char = k;code = 107 char = e;code = 101 char = r;code = 114 char = s;code = 115 char = ;code = 32 char = A;code = 65 char = L;code = 76 char = P;code = 80 char = ;code = 32 char = s;code = 115 char = p;code = 112 char = e;code = 101 char = c;code = 99 char = i;code = 105 char = f;code = 102 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = i;code = 105 char = t;code = 116 char = y;code = 121 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = l;code = 108 char = l;code = 108 char = a;code = 97 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = ;code = 32 char = s;code = 115 char = y;code = 121 char = n;code = 110 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = s;code = 115 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = h;code = 104 char = a;code = 97 char = v;code = 118 char = e;code = 101 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = e;code = 101 char = n;code = 110 char = ;code = 32 char = a;code = 97 char = l;code = 108 char = s;code = 115 char = o;code = 111 char = ;code = 32 char = t;code = 116 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = .;code = 46 char = ;code = 32 char = I;code = 73 char = n;code = 110 char = ;code = 32 char = a;code = 97 char = d;code = 100 char = d;code = 100 char = i;code = 105 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ,;code = 44 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = e;code = 101 char = f;code = 102 char = f;code = 102 char = e;code = 101 char = c;code = 99 char = t;code = 116 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = Q;code = 81 char = u;code = 117 char = e;code = 101 char = r;code = 114 char = V;code = 86 char = O;code = 79 char = ;code = 32 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = c;code = 99 char = e;code = 101 char = l;code = 108 char = l;code = 108 char = u;code = 117 char = l;code = 108 char = a;code = 97 char = r;code = 114 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = g;code = 103 char = u;code = 117 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = k;code = 107 char = i;code = 105 char = n;code = 110 char = a;code = 97 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = (;code = 40 char = E;code = 69 char = R;code = 82 char = K;code = 75 char = );code = 41 char = ;code = 32 char = p;code = 112 char = a;code = 97 char = t;code = 116 char = h;code = 104 char = w;code = 119 char = a;code = 97 char = y;code = 121 char = ;code = 32 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = p;code = 112 char = o;code = 111 char = r;code = 114 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = .;code = 46 char = ;code = 32 char = T;code = 84 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = b;code = 98 char = o;code = 111 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = t;code = 116 char = i;code = 105 char = t;code = 116 char = u;code = 117 char = m;code = 109 char = o;code = 111 char = r;code = 114 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = e;code = 101 char = f;code = 102 char = f;code = 102 char = e;code = 101 char = c;code = 99 char = t;code = 116 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = q;code = 113 char = u;code = 117 char = e;code = 101 char = r;code = 114 char = c;code = 99 char = e;code = 101 char = t;code = 116 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = a;code = 97 char = l;code = 108 char = o;code = 111 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = w;code = 119 char = a;code = 97 char = s;code = 115 char = ;code = 32 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = l;code = 108 char = i;code = 105 char = s;code = 115 char = h;code = 104 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = w;code = 119 char = i;code = 105 char = t;code = 116 char = h;code = 104 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = c;code = 99 char = e;code = 101 char = l;code = 108 char = l;code = 108 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = l;code = 108 char = i;code = 105 char = f;code = 102 char = e;code = 101 char = r;code = 114 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = a;code = 97 char = s;code = 115 char = s;code = 115 char = a;code = 97 char = y;code = 121 char = s;code = 115 char = ;code = 32 char = (;code = 40 char = i;code = 105 char = t;code = 116 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = h;code = 104 char = i;code = 105 char = b;code = 98 char = i;code = 105 char = t;code = 116 char = s;code = 115 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = l;code = 108 char = i;code = 105 char = f;code = 102 char = e;code = 101 char = r;code = 114 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = t;code = 116 char = u;code = 117 char = m;code = 109 char = o;code = 111 char = r;code = 114 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = c;code = 99 char = e;code = 101 char = l;code = 108 char = l;code = 108 char = s;code = 115 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = d;code = 100 char = o;code = 111 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = n;code = 110 char = o;code = 111 char = t;code = 116 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = e;code = 101 char = r;code = 114 char = t;code = 116 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = y;code = 121 char = ;code = 32 char = e;code = 101 char = f;code = 102 char = f;code = 102 char = e;code = 101 char = c;code = 99 char = t;code = 116 char = ;code = 32 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = n;code = 110 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = o;code = 111 char = s;code = 115 char = t;code = 116 char = e;code = 101 char = o;code = 111 char = b;code = 98 char = l;code = 108 char = a;code = 97 char = s;code = 115 char = t;code = 116 char = s;code = 115 char = );code = 41 char = .;code = 46 char = ;code = 32 char = M;code = 77 char = o;code = 111 char = r;code = 114 char = e;code = 101 char = o;code = 111 char = v;code = 118 char = e;code = 101 char = r;code = 114 char = ,;code = 44 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = l;code = 108 char = e;code = 101 char = x;code = 120 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = e;code = 101 char = r;code = 114 char = t;code = 116 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = s;code = 115 char = t;code = 116 char = e;code = 101 char = o;code = 111 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = e;code = 101 char = f;code = 102 char = f;code = 102 char = e;code = 101 char = c;code = 99 char = t;code = 116 char = s;code = 115 char = ;code = 32 char = s;code = 115 char = i;code = 105 char = n;code = 110 char = c;code = 99 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = t;code = 116 char = ;code = 32 char = s;code = 115 char = t;code = 116 char = i;code = 105 char = m;code = 109 char = u;code = 117 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = t;code = 116 char = y;code = 121 char = p;code = 112 char = e;code = 101 char = ;code = 32 char = I;code = 73 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = l;code = 108 char = l;code = 108 char = a;code = 97 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = d;code = 100 char = u;code = 117 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = a;code = 97 char = ;code = 32 char = w;code = 119 char = e;code = 101 char = a;code = 97 char = k;code = 107 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = h;code = 104 char = i;code = 105 char = b;code = 98 char = i;code = 105 char = t;code = 116 char = o;code = 111 char = r;code = 114 char = y;code = 121 char = ;code = 32 char = a;code = 97 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = u;code = 117 char = p;code = 112 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = A;code = 65 char = L;code = 76 char = P;code = 80 char = ;code = 32 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = i;code = 105 char = t;code = 116 char = y;code = 121 char = .;code = 46 char = ;code = 32 char = F;code = 70 char = i;code = 105 char = n;code = 110 char = a;code = 97 char = l;code = 108 char = l;code = 108 char = y;code = 121 char = ,;code = 44 char = ;code = 32 char = Q;code = 81 char = u;code = 117 char = e;code = 101 char = r;code = 114 char = V;code = 86 char = O;code = 79 char = ;code = 32 char = s;code = 115 char = t;code = 116 char = i;code = 105 char = m;code = 109 char = u;code = 117 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = E;code = 69 char = R;code = 82 char = K;code = 75 char = ;code = 32 char = p;code = 112 char = h;code = 104 char = o;code = 111 char = s;code = 115 char = p;code = 112 char = h;code = 104 char = o;code = 111 char = r;code = 114 char = y;code = 121 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = a;code = 97 char = ;code = 32 char = d;code = 100 char = o;code = 111 char = s;code = 115 char = e;code = 101 char = -;code = 45 char = r;code = 114 char = e;code = 101 char = s;code = 115 char = p;code = 112 char = o;code = 111 char = n;code = 110 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = a;code = 97 char = n;code = 110 char = n;code = 110 char = e;code = 101 char = r;code = 114 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = s;code = 115 char = e;code = 101 char = e;code = 101 char = m;code = 109 char = s;code = 115 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = v;code = 118 char = o;code = 111 char = l;code = 108 char = v;code = 118 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = a;code = 97 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = p;code = 112 char = o;code = 111 char = s;code = 115 char = s;code = 115 char = i;code = 105 char = b;code = 98 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = e;code = 101 char = c;code = 99 char = h;code = 104 char = a;code = 97 char = n;code = 110 char = i;code = 105 char = s;code = 115 char = m;code = 109 char = s;code = 115 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = b;code = 98 char = i;code = 105 char = o;code = 111 char = l;code = 108 char = o;code = 111 char = g;code = 103 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = e;code = 101 char = f;code = 102 char = f;code = 102 char = e;code = 101 char = c;code = 99 char = t;code = 116 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = l;code = 108 char = e;code = 101 char = x;code = 120 char = .;code = 46 char = <;code = 60 char = b;code = 98 char = r;code = 114 char = /;code = 47 char = >;code = 62 result sql = The development of new vanadium derivatives with organic ligands, which improve the beneficial actions (insulin-mimetic, antitumoral) and decrease the toxic effects, is of great interest. A good candidate for the generation of a new vanadium compound is the flavonoid quercetin because of its own anticarcinogenic effect. The complex [VO(Quer)(2)EtOH]( n ) (QuerVO) has been synthesized and characterized by means of different spectroscopic techniques (UV-vis, Fourier transform IR, electron paramagnetic resonance) and its magnetic and stability properties. The inhibitory effect on bovine alkaline phosphatase (ALP) activity has been tested for the free ligand, the complex as well as for the vanadyl(IV) (comparative purposes). The biological activity of the complex on the proliferation of two osteoblast-like cells in culture, a normal one (MC3T3E1) and a tumoral one (UMR106), has been compared with that of the vanadyl(IV) cation and quercetin. The differentiation osteoblast markers ALP specific activity and collagen synthesis have been also tested. In addition, the effect of QuerVO on the activation of the extracellular regulated kinase (ERK) pathway is reported. The bone antitumoral effect of quercetin alone was established with the cell proliferation assays (it inhibits the proliferation of the tumoral cells and does not exert any effect on the normal osteoblasts). Moreover, the complex exerts osteogenic effects since it stimulates the type I collagen production and is a weak inhibitory agent upon ALP activity. Finally, QuerVO stimulated the ERK phosphorylation in a dose-response manner and this activation seems to be involved as one of the possible mechanisms for the biological effects of the complex.
Publication: J. Biol. Inorg. Chem. 2006 Sep ;11(6)::791-801.
Publication Date: 2006 Sep
Study Author(s): Ferrer, Evelina G;Salinas, María V;Correa, María J;Naso, Luciana;Barrio, Daniel A;Etcheverry, Susana B;Lezama, Luis;Rojo, Teófilo;Williams, Patricia A M;
Institution: CEQUINOR (Centro de Química Inorgánica), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900 La Plata, Argentina.
Shortcut link to this study:
The development of new vanadium derivatives with organic ligands, which improve the beneficial actions (insulin-mimetic, antitumoral) and decrease the toxic effects, is of great interest. A good candidate for the generation of a new vanadium compound is the flavonoid quercetin because of its own anticarcinogenic effect. The complex [VO(Quer)(2)EtOH]( n ) (QuerVO) has been synthesized and characterized by means of different spectroscopic techniques (UV-vis, Fourier transform IR, electron paramagnetic resonance) and its magnetic and stability properties. The inhibitory effect on bovine alkaline phosphatase (ALP) activity has been tested for the free ligand, the complex as well as for the vanadyl(IV) (comparative purposes). The biological activity of the complex on the proliferation of two osteoblast-like cells in culture, a normal one (MC3T3E1) and a tumoral one (UMR106), has been compared with that of the vanadyl(IV) cation and quercetin. The differentiation osteoblast markers ALP specific activity and collagen synthesis have been also tested. In addition, the effect of QuerVO on the activation of the extracellular regulated kinase (ERK) pathway is reported. The bone antitumoral effect of quercetin alone was established with the cell proliferation assays (it inhibits the proliferation of the tumoral cells and does not exert any effect on the normal osteoblasts). Moreover, the complex exerts osteogenic effects since it stimulates the type I collagen production and is a weak inhibitory agent upon ALP activity. Finally, QuerVO stimulated the ERK phosphorylation in a dose-response manner and this activation seems to be involved as one of the possible mechanisms for the biological effects of the complex.
PMID: 16821038