1. A device for a gym machine comprising a frame (2), at least one resistant load (3) mounted on the frame having at least one coupling surface (4), at least one flexible cable (5) associated with the resistant load (3) for performing a physical exercise, the device comprising at least one support (6) designed to be rigidly associated with the resistant load (3) at the coupling surface (4), at least one shaft (7) rotatably coupled to the support (6) on a first axis (8) at a first portion (9) and having a second portion (10) with a second, eccentric axis (11), power drive means (12) for rotationally driving the shaft (7) about the first axis (8), the shaft (7) being associated with the flexible cable (5) at the second portion (10) in such a way as to generate vibrations along the flexible cable (5).
2. The device according to claim 1, wherein the support comprises a first bracket (13) to which the first portion (9) of the shaft (7) is rotatably coupled to rotate about the first axis (8).
3. The device according to claim 2, wherein the first bracket (13) is U-shaped and has at least two coaxial annular grooves (14) for receiving respective bearings for coupling to the shaft (7).
4. The device according to claim 1, wherein the support (6) comprises a second bracket (15) for mounting the power drive means (12); said power drive means (12) comprising at least one motor (16) for driving at least one drive pulley (17) at least one predetermined rotation speed.
5. The device according to claim 4, comprising at least one driven pulley (18) keyed to the shaft (7); the drive pulley (17) being connected to the driven pulley (18) by a belt (19) so as to transmit rotational drive to the shaft (7).
6. The device according to claim 5, wherein the driven pulley (18) is keyed rigidly to the shaft (7) at a middle portion (20) by means of a key (21).
7. The device according to claim 1, comprising coupling means (22) freely rotatably associated with the shaft (7), at the second portion (10), on the second eccentric axis (11); the coupling means (22) being designed to connect the shaft (7) to the flexible cable (5) in such a way that the rotation of the shaft (7) about the first axis (8) causes the coupling means (22) to oscillate, thereby creating vibrations along the flexible cable (5).
8. The device according to claim 7, wherein the coupling means (22) comprise at least one idler pulley (23) freely rotatably associated with the shaft (7), at the second portion (10), on the second eccentric axis (11); the idler pulley (23) being designed to have the flexible cable (5) wound around it to apply an action opposing the resistant load (3) in such a way that the rotation of the shaft (7) about the first axis (8) causes the idler pulley (23) to oscillate, thereby creating vibrations along the flexible cable (5).
9. The device according to claim 8, wherein the idler pulley (23) is coupled to the second portion (10) by an interposed first bearing (24).
10. The device according to claim 9, wherein the second portion (10) has a threaded end part (25) for fastening the internal ring of the first bearing (24) to the shaft (7) with a bolt.
11. The device according to claim 7, wherein the coupling means (22) comprise at least one ring (26) freely rotatably associated with the shaft (7), at the second portion (10), on the second eccentric axis (11); the ring (26) being rigidly associated with one end (27) of the flexible cable (5) to apply an action opposing the resistant load (3) in such a way that the rotation of the shaft (7) about the first axis (8) causes the ring (26) to oscillate, thereby creating vibrations along the flexible cable (5).
12. The device according to claim 11, wherein the ring (26) has a radial seat (28) for rigidly housing the end (27) of the flexible cable (5).
13. The device according to claim 11, wherein the ring (26) comprises a radial cylindrical threaded extension (29); the flexible cable (5) being integrally connected at its end (27) to an internally threaded pipe (30) designed to be screwed to the ring (26) at the cylindrical extension (29), in such a way as to fix the flexible cable (5) to the ring (26).
14. The device according to claim 1, especially for weight-stack gym machines, where the resistant load (3) is mounted on the frame (2) slidably on vertical guides (2a) and whose top surface (4a) comprises the coupling surface (4), wherein the support (6) is rigidly fixed to the resistant load (3) at the coupling surface (4) by screw means (6a).
15. The device according to claim 14, comprising at least two cylindrical spacers (6b) having respective axial holes (6c) for the passage of respective screws (6d) designed to be screwed into corresponding threaded holes (6e) made in the resistant load (3) in order to fasten the support (6).
16. The device according to claim 1, wherein the device is removable.
The claims below are in addition to those above.
All refrences to claims which appear below refer to the numbering after this setence.
1. A compound of Formula I:
wherein:
R1 and R2 are each independently a member selected from the group consisting of hydrogen, and a hydroxyl group;
m and n are each independently selected from about 0-2;
R3 is selected from the group consisting of \u2014NR4R5 wherein R4 and R5 are each independently a member selected from the group consisting of a hydrogen, a saccharide residue, an optionally substituted alkyl, an optionally substituted acyl, an optionally substituted acyloxy, and a quaternary ammonium salt \u2014NR6R7R8X wherein R6, R7 and R8 are independently a member selected from the group consisting of hydrogen and C1-C4 alkyl, and X is the negatively charged ionically bound counterion selected from the group consisting of halogen and an optionally substituted carboxylate.
2. The compound of claim 1, wherein R1 and R2 are both hydroxyl groups.
3. The compound of claim 1, wherein m and n are each 1.
4. The compound of claim 3, wherein said compound has Formula II:
5. The compound of claim 1, wherein R4 is hydrogen; and
R5 is a member selected from the group consisting of a hydrogen, a saccharide residue, an optionally substituted alkyl, an optionally substituted acyl, and an optionally substituted acyloxy.
6. The compound of claim 3, wherein said compound has Formula III:
7. The compound of claim 5, wherein R5 is succinyl.
8. The compound of claim 5, wherein R5 is acyloxy.
9. The compound of claim 1, wherein R3 is a trimethylammonium salt.
10. The compound of claim 1, wherein R3 is a triethylammonium salt.
11. A composition for delivering an agent to a cell, the composition comprising the agent and a delivery enhancing compound of Formula I:
wherein:
R1 and R2 are each independently a member selected from the group consisting of hydrogen, and a hydroxyl group;
m and n are each independently selected from about 0-2;
R3 is selected from the group consisting of \u2014NR4R5 wherein R4 and R5 are each independently a member selected from the group consisting of a hydrogen, a saccharide residue, an optionally substituted alkyl, an optionally substituted acyl, an optionally substituted acyloxy, and a quaternary ammonium salt \u2014NR6R7R8X wherein R6, R7 and R8 are independently a member selected from the group consisting of hydrogen and C1-C4 alkyl, and X is the negatively charged ionically bound counterion selected from the group consisting of halogen and an optionally substituted carboxylate.
12. The composition according to claim 11, wherein R1 and R2 are both hydroxyl groups.
13. The composition according to claim 11, wherein m and n are each 1.
14. The composition according to claim 13, wherein said composition has Formula II:
15. The composition according to claim 11, wherein R4 is hydrogen; and
R5 is a member selected from the group consisting of a hydrogen, a saccharide residue, an optionally substituted alkyl, an optionally substituted acyl, and an optionally substituted acyloxy.
16. The composition according to claim 15, wherein said composition has Formula III:
17. The composition according to claim 15, wherein R5 is succinyl.
18. The composition according to claim 15, wherein R5 is acyloxy.
19. The composition according to claim 11, wherein R3 is a trimethylammonium salt.
20. The composition according to claim 11, wherein R3 is a triethylammonium salt.
21. The composition according to claim 11, wherein said agent is a diagnostic agent.
22. The composition according to claim 11, wherein said agent modulates a biological process in a cell when the agent is present in the cell.
23. The composition according to claim 22, wherein the biological process is selected from the group consisting of cell growth, differentiation, proliferation, a metabolic or biosynthetic pathway, gene expression, a disease-associated process, and an immune response.
24. The composition according to claim 11, wherein said agent comprises a polynucleotide or protein.
25. The composition according to claim 24, wherein said polynucleotide is selected from the group consisting of an antisense nucleic acid, a triplex-forming nucleic acid, and a nucleic acid that comprises a gene which encodes a polypeptide that modulates a biological process.
26. The composition according to claim 25, wherein the gene is a tumor suppressor gene.
27. The composition according to claim 26, wherein the tumor suppressor gene is selected from the group consisting of a retinoblastoma gene and a p53 gene.
28. The composition according to claim 11, wherein the composition further comprises a polymeric matrix.
29. The composition according to claim 11, wherein the composition further comprises a mucoadhesive.
30. The composition according to claim 24, wherein said agent comprises a protein.
31. The composition according to claim 30, wherein said protein is an interferon.
32. The method of claim 31, wherein the interferon is selected from the group consisting of interferon-\u03b1, interferon-\u03b2, interferon-\u03b4, and interferon-\u03b3, and a fusion interferon thereof.
33. The method of claim 31, wherein the interferon is selected from the group consisting of interferon \u03b1-2\u03b2, a fusion interferon is \u03b1-2\u03b1-1, and interferon \u03b1-2e.
34. The method of claim 31, wherein the in the interferon is human \u03b11 or \u03b12 interferon.
35. The composition according to claim 30, wherein said protein is an antibody.
36. The composition according to claim 35, wherein said antibody is selected from the group consisting of anti-interferon-\u03b1, anti-interferon-\u03b2, anti-interferon-\u03b4, anti-interferon-\u03b3, an anti-interleukin, anti-IL-1, anti-IL-2, anti-IL-4, anti-Il-6, anti-IL-7 and anti-IL-10.
37. A method of delivering an agent to a cell, said method comprising administering said agent to said cell in a composition comprising a compound of Formula I:
wherein:
R1 and R2 are each independently a member selected from the group consisting of hydrogen, and a hydroxyl group;
m and n are each independently selected from about 0-2;
R3 is selected from the group consisting of \u2014NR4R5 wherein R4 and R5 are each independently a member selected from the group consisting of a hydrogen, a saccharide residue, an optionally substituted alkyl, an optionally substituted acyl, an optionally substituted acyloxy, and a quaternary ammonium salt \u2014NR6R7R8X wherein R6, R7 and R8 are independently a member selected from the group consisting of hydrogen and C1-C4 alkyl, and X is the negatively charged ionically bound counterion selected from the group consisting of halogen and an optionally substituted carboxylate.
38. A method of treating bladder cancer by the administration of a recombinant viral vector encoding a cytostatic or a tumor suppressor gene in combination with a compound of Formula I:
wherein:
R1 and R2 are each independently a member selected from the group consisting of hydrogen, and a hydroxyl group;
m and n are each independently selected from about 0-2;
R3 is selected from the group consisting of \u2014NR4R5 wherein R4 and R5 are each independently a member selected from the group consisting of a hydrogen, a saccharide residue, an optionally substituted alkyl, an optionally substituted acyl, and an optionally substituted acyloxy, and a quaternary ammonium salt \u2014NR6R7R8X wherein R6, R7 and R8 are independently a member selected from the group consisting of hydrogen and C1-C4 alkyl, and X is the negatively charged ionically bound counterion selected from the group consisting of halogen and an optionally substituted carboxylate.
39. The method of claim 38, wherein said tumor suppressor gene is selected from the group consisting of RB56, RB110, RB94, P53, and P53 delta13-19.
40. The method of claim 38, wherein said cytostatic gene is a gene for interferon.
41. The method of claim 40, wherein the interferon is selected from the group consisting of interferon-\u03b1, interferon-\u03b2, interferon-\u03b4, and interferon-\u03b3, and a fusion interferon thereof.
42. The method of claim 40, wherein the interferon is selected from the group consisting of interferon \u03b1-2\u03b2, a fusion interferon is \u03b1-2\u03b1-1, and interferon \u03b1-2e.
43. The method of claim 40, wherein the in the interferon is human \u03b11 or \u03b12 interferon.
44. The method of claim 38, wherein said bladder cancer is superficial bladder cancer.
45. The method of claim 38, wherein said compound of Formula I further comprises a solubilizing agent.
46. The method of claim 37, wherein the agent is a therapeutic agent.
47. The method of claim 37, wherein the agent is a diagnostic agent.
48. The method of claim 37, wherein the concentration of the delivery enhancing compound is about 0.002 to about 2 mgml.
49. The method of claim 48, wherein the concentration of the delivery enhancing compound is about 0.02 to about 2 mgml.
50. The method of claim 49, wherein the concentration of the delivery enhancing compound is about 0.2 to 2 mgml.
51. The method of claim 37, wherein the delivery-enhancing compound is soluble in an aqueous solution in the absence of a detergent other than the delivery-enhancing compound.
52. The method of claim 51, wherein the solubility of the delivery-enhancing compound in aqueous solution is at least about 1 mgml in the absence of a detergent other than the delivery-enhancing compound.
53. The method of claim 37, wherein the agent is delivered across an glycosaminoglycans (GAG) layer.
54. The method of claim 53, wherein the GAG layer comprises an organ.
55. The method of claim 53, wherein the GAG layer comprises an epithelial tissue.
56. The method of claim 55, wherein the epithelial tissue is selected from the group consisting of gastrointestinal tract, skin, lung, and mucosa.
57. The method of claim 37, wherein the administration is by intravesical administration.
58. The method of claim 37, wherein the agent is a protein.
59. The method of claim 37, wherein the agent is a gene.
60. The method of claim 59, wherein the gene is administered in a vector.
61. The method of claim 60, wherein the vector is a viral vector.
62. The method of claim 37, wherein the viral vector is selected from the group consisting of an adenoviral vector, a retroviral vector, and an adeno-associated viral vector.
63. The method of claim 37, wherein the viral vector is administered as a suspension having a viral vector concentration of from 1\xd7108 particlesml to 5\xd71011 particlesml.
64. The method of claim 63, wherein the viral vector concentration in the suspension is from 1\xd7109 particlesml to 1\xd71011 particlesml.
65. The method of claim 59, wherein the gene is a therapeutic gene.
66. The method of claim 65, wherein the therapeutic gene is a tumor suppressor gene.
67. The method of claim 66, wherein the tumor suppressor gene is p53.
68. The method of claim 66, wherein the tumor suppressor gene is a retinoblastoma gene.
69. The method of claim 68, wherein the retinoblastoma tumor suppressor gene encodes full length RB protein.
70. The method of claim 68, wherein the retinoblastoma tumor suppressor gene encodes p56RB.
71. The method of claim 65, wherein the cells are cancer cells.
72. The method of claim 71, wherein the cancer cells are bladder cancer cells.
73. The method of claim 71, wherein the cancer cells are provided as a tissue.
74. The method of claim 38, wherein the delivery-enhancing compound is administered prior to administration of the agent.
75. The method of claim 38, wherein the delivery enhancing compound is administered with the agent.