What is claimed:
1. An ergonomically designed stringed instrument comprising:
a main body portion having first and second spaced distal end faces longitudinally thereof, and spaced distal top and bottom faces vertically thereof, and spaced front and rear surfaces;
an elongated fingerboard extending from a first one of said end faces;
a bridge for supporting strings of the instrument disposed closely adjacent to the second one of the end faces and the bottom face;
a leg rest attached to the first end face and extending therefrom, said leg rest being angularly adjustable between selectable supporting positions;
an upper horn extending from a region of the top face of the body, said upper horn having a contoured rear surface shaped to conformingly engage the upper body of the instrumentalist; and
a belly rest extending from the rear surface of the instrument for engagement with an instrumentalist’s abdomen.
2. The instrument of claim 1 wherein the legrest assembly comprises:
a support lever pivotally connected to the main body of the instrument about a pivot axis, said support lever being shaped to rest on support surfaces in various angular positions,
a keeper plate mounted on the body of the instrument, said keeper plate having a plurality of spaced keeper holes disposed along an arc for fixing the support lever in said various angular positions; and
a rockable latch plate having an actuator portion engageable by an instrumentalist and having a locking pin extending therefrom, said locking pin being insertable into a selected one of said keeper holes for locking said support lever at one of said various angular positions.
3. The instrument of claim 2 wherein said rockable latch plate is spring biased to normally hold said locking pin in the selected one of said keeper holes.
4. The instrument of claim 1 further including an armrest connectable to the rear side of the instrument body adjacent to the second end face.
5. The instrument of claim 4 wherein the armrest comprises:
a support arm extending from the instrument;
a slide mounted on the support arm;
a pressure adjustment device for clamping the slide in fixed positions along the support arm; and
an arm support member mounted on the slide for supporting the arm of an instrumentalist.
6. The stringed instrument of claim 5 wherein said pressure adjustment device includes a manually actuated wedge member movable between the slide and the arm support member to force the slide against the support member in locking engagement.
7. The instrument of claim 6 further including a spring resiliently holding the wedge in position.
8. The instrument of claim 7 wherein the spring is a flexible plate.
9. The instrument of claim 4 further including a side rest assembly connecting the armrest to an instrumentalist’s side for stability.
10. The instrument of claim 9 wherein the siderest assembly comprises:
an elongated support plate having a first distal end for engaging a side of an instrumentalist and a second distal end connectable to a body of the instrument, said support plate being bent between the distal ends about a transverse axis therethrough such that the plate is rockable about the transverse axis by forces generated between the instrumentalist’s side and the instrument body;
a base plate conformably shaped to support the elongated plate and having a guide slot therein between the second distal end of the support plate and the transverse axis thereof; and
a pressure plate for supporting the base plate beneath the guide slot, and having a ridge extending into and movable longitudinally of the guide slot;
whereby rocking of the support plate about the transverse axis thereof varies pressure between the base plate and pressure plate to facilitate relative positioning of the ridge within the guide slot, and thus the support plate.
11. The instrument of claim 9 wherein the siderest assembly is adjustable.
12. The instrument of claim 1 further including a fixed tremolo bar readily adjustable to raised or lowered positions by the fingers of the instrumentalist’s right hand during playing.
13. The instrument of claim 12 further including a tremolo locking mechanism.
14. The instrument of claim 13 wherein the tremolo bar locking mechanism comprises:
a tremolo bar fixed at one end adjacent a bridge of the stringed instrument on the main body thereof such that the tremolo bar is normally free to vibrate;
a slidable latch bar transversely movable under the tremolo bar upon actuation by an instrumentalist;
a guide plate for holding the latch bar having a slot for accommodating sliding movement thereof; and
a first spring for biasing the latch bar against the guide plate.
15. The instrument of claim 14 further including a second spring for resiliently engaging an end of the latch bar when in a locked position thereof.
16. The instrument of claim 1 further including a holder for removably storing a pick.
17. The instrument of claim 16 wherein said holder comprises:
a cavity formed in the main body for receiving a pick, and an entry slot in said cavity for frictionally engaging the pick.
18. The instrument of claim 17 wherein said entry slot is lined with rubber.
19. The instrument of claim 17 wherein the entry slot is formed in a rubber sheet.
20. The instrument of claim 17 wherein the cavity is filled with a sponge beneath the entry slot for gripping the pick.
21. The instrument of claim 1 wherein bottom face of the body is shaped to rest on a right thigh of the instrumentalist.
22. The instrument of claim 3 wherein the armrest is connected to the body by a universal coupling to thereby permit selected diverse types of armrests to be attached to the instrument body.
23. A legrest assembly for a string instrument comprising:
a support lever pivotally connected to a body of the instrument about a pivot axis, said support lever being shaped to rest on a support surface in various angular positions;
a keeper plate mounted on the body of the instrument, said keeper plate having a plurality of spaced keeper holes disposed along an arc for fixing the support lever in said various angular positions; and
a rockable latch plate having an actuator portion engageable by an instrumentalist and a locking pin extending therefrom, said locking pin extending therefrom, said locking pin being insertable into a selected one of said keeper holes for locking said support lever at one of said various angular positions.
24. The legrest assembly of claim 23 wherein said rockable latch is spring biased to normally hold said locking pin in the selected one of said keeper holes.
25. The armrest assembly for a stringed instrument comprising:
a support arm extending from the instrument;
a slide mounted on the support arm;
a pressure adjustment device for clamping the slide in fixed positions along the support arm; and
an arm support member mounted on the slide for supporting the arm of an instrumentalist.
26. The armrest assembly of claim 25 wherein said pressure adjustment device includes a manually actuated wedge member movable between the side and the arm support member to force the slide against the support member in locking engagement.
27. The armrest assembly of claim 26 further including a spring resiliently holding the wedge in position.
28. The armrest assembly of claim 27 wherein the spring is a flexible plate.
29. A siderest assembly for a stringed instrument comprising:
an elongated support plate having a first distal end for engaging a side of an instrumentalist and a second distal end connectable to a body of the instrument, said support plate being bent between the distal ends about a transverse axis therethrough such that the plate is rockable about the transverse axis by forces generated between the instrumentalist’s side and the instrument body;
a base plate conformably shaped to support the elongated plate and having a guide slot therein between the second distal end of the support plate and the transverse axis thereof; and
a pressure plate for supporting the base plate beneath the guide slot, and having a ridge extending into and movable longitudinally of the guide slot;
whereby rocking of the support plate about the transverse axis thereof varies pressure between the base plate and pressure plate to facilitate relative positioning of the ridge within the guide slot, and thus the support plate.
30. The tremolo bar locking assembly for use on a string instrument comprising:
a tremolo bar fixed at one end adjacent a bridge of the stringed instrument on the main body thereof such that the tremolo bar is normally free to vibrate;
a slidable latch bar transversely movable under the tremolo bar upon actuation by an instrumentalist;
a guide plate for holding the latch bar having a slot for accommodating sliding movement thereof; and
a first spring for biasing the latch bar against the guide plate.
31. The tremolo bar assembly of claim 30 further including a second spring for resiliently engaging an end of the latch bar when in a locked position thereof.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
What is claimed:
1. A recombinant nucleic acid vector comprising a first expression cassette comprising a first promoter operably linked to a nucleic acid sequence encoding a syncytium-inducing polypeptide, wherein said first expression cassette is flanked on either side by a site recognized by a recombinase.
2. The recombinant nucleic acid vector of claim 1, further comprising a second expression cassette comprising a tissue-specific promoter operably linked to a nucleic acid sequence encoding said recombinase.
3. The recombinant nucleic acid vector of claim 1, wherein said first promoter is active in malignant cells, and wherein said tissue specific promoter is active in non-malignant cells of the same lineage as said malignant cells but is substantially inactive in said malignant cells.
4. The recombinant nucleic acid vector of claim 1, wherein said recombinase is selected from the group consisting of Cre recombinase, FLP recombinase, Gin recombinase, Pin recombinase, and lambda phage Integrase, and said site is susceptible to cleavage with said recombinase.
5. The recombinant nucleic acid vector of claim 1, wherein said first promoter is a tumor-specific promoter.
6. The recombinant nucleic acid vector of claim 5, wherein said tumor specific promoter is selected from the group consisting of a carcinoembryonic antigen promoter, an alphafetoprotein promoter, a tyrosinase promoter, an Erb-B2 promoter and a myelin basic protein promoter.
7. The recombinant nucleic acid vector of claim 1, wherein said sequence which encodes a syncytium-inducing polypeptide encodes an FMG.
8. The recombinant nucleic acid vector of claim 7, wherein said FMG is a viral FMG.
9. The recombinant nucleic acid vector of claim 8, wherein said viral FMG is selected from the group consisting of type G membrane glycoprotein of rabies virus, type G membrane glycoprotein of Mokola virus, type G membrane glycoprotein of vesicular stomatitis virus, type G membrane glycoprotein of Togaviruses, murine hepatitis virus JHM surface projection protein, porcine respiratory coronavirus spike glycoprotein, porcine respiratory coronavirus membrane glycoprotein, avian infectious bronchitis spike glycoprotein and its precursor, bovine enteric coronavirus spike protein, paramyxovirus SV5 F protein, Measles virus F protein, canine distemper virus F protein, Newcastle disease virus F protein, human parainfluenza virus 3 F protein, simian virus 41 F protein, Sendai virus F protein, human respiratory syncytial virus F protein, Measles virus hemagglutinin, simian virus 41 hemagglutinin neuraminidase proteins, human parainfluenza virus type 3 hemagglutinin neuraminidase, Newcastle disease virus hemagglutinin neuraminidase, human herpesvirus 1 gH, simian varicella virus gH, human herpesvirus gB proteins, bovine herpesvirus gB proteins, cercopithecine herpesvirus gB proteins, Friend murine leukemia virus envelope glycoprotein, Mason Pfizer monkey virus envelope glycoprotein, HIV envelpoe glycoprotein, influenza virus hemaglutinin, poxvirus membrane glycoproteins, mumps virus hemaglutinin neuraminidase, mumps virus glycoproteins F1 and F2, West Nile virus membrane glycoprotein, herpes simplex virus membrane glycoprotein, Russian Far East encephalitis virus membrane glycoprotein, Venezuelan equine encephalitis virus membrane glycoprotein and varicella virus membrane glycoprotein.
10. The recombinant nucleic acid vector of claim 1, wherein said vector is a retroviral vector.
11. A cell comprising a vector of claim 1.
12. A recombinant expression cassette system comprising a first expression cassette comprising a first promoter operably linked to a nucleic acid sequence encoding a syncytium-inducing polypeptide, wherein said first expression cassette is flanked on either side by a site recognized by a recombinase; and a second expression cassette comprising a tissue-specific promoter operably linked to a nucleic acid sequence encoding said recombinase.
13. The expression cassette system of claim 12, wherein said first and said second expression cassettes are encoded on a single vector nucleic acid.
14. The expression cassette system of claim 12, wherein said first and said second expression cassettes are encoded on separate nucleic acid vectors.
15. The expression cassette system of claim 12, wherein said first promoter is active in malignant cells, and wherein said tissue specific promoter is active in non-malignant cells of the same lineage as said malignant cells but is substantially inactive in said malignant cells.
16. The expression cassette system of claim 12, wherein said recombinase is selected from the group consisting of Cre recombinase, FLP recombinase, Gin recombinase, Pin recombinase, and lambda phage Integrase, and said site is susceptible to cleavage with said recombinase.
17. The expression cassette system of claim 12, wherein said first promoter is a tumor specific promoter.
18. The expression cassette system of claim 17, wherein said tumor specific promoter is selected from the group consisting of a carcinoembryonic antigen promoter, an alphafetoprotein promoter, a tyrosinase promoter, an Erb-B2 promoter and a myelin basic protein promoter.
19. The expression cassette system of claim 12, wherein said sequence which encodes a syncytium-inducing polypeptide encodes an FMG.
20. The expression cassette system of claim 19, wherein said FMG is a viral FMG.
21. The expression cassette system of claim 20 wherein said viral FMG is selected from the group consisting of type G membrane glycoprotein of rabies virus, type G membrane glycoprotein of Mokola virus, type G membrane glycoprotein of vesicular stomatitis virus, type G membrane glycoprotein of Togaviruses, murine hepatitis virus JHM surface projection protein, porcine respiratory coronavirus spike glycoprotein, porcine respiratory coronavirus membrane glycoprotein, avian infectious bronchitis spike glycoprotein and its precursor, bovine enteric coronavirus spike protein, paramyxovirus SV5 F protein, Measles virus F protein, canine distemper virus F protein, Newcastle disease virus F protein, human parainfluenza virus 3 F protein, simian virus 41 F protein, Sendai virus F protein, human respiratory syncytial virus F protein, Measles virus hemagglutinin, simian virus 41 hemagglutinin neuraminidase proteins, human parainfluenza virus type 3 hemagglutinin neuraminidase, Newcastle disease virus hemagglutinin neuraminidase, human herpesvirus 1 gH, simian varicella virus gH, human herpesvirus gB proteins, bovine herpesvirus gB proteins, cercopithecine herpesvirus gB proteins, Friend murine leukemia virus envelope glycoprotein, Mason Pfizer monkey virus envelope glycoprotein, HIV envelope glycoprotein, influenza virus hemaglutinin, poxvirus membrane glycoproteins, mumps virus hemaglutinin neuraminidase, mumps virus glycoproteins F1 and F2, West Nile virus membrane glycoprotein, herpes simplex virus membrane glycoprotein, Russian Far East encephalitis virus membrane glycoprotein, Venezuelan equine encephalitis virus membrane glycoprotein and varicella virus membrane glycoprotein.
22. The expression cassette system of any one of claims 12, wherein said expression cassette system is encoded one or more retroviral vectors.
23. A cell comprising the expression cassette system of claims 12.
24. A therapeutic composition comprising a cell of any one of claims 1 or 12 in admixture with a physiologically acceptable carrier.
25. A method of reducing tumor size, said method comprising the step of:
(a) permitting expression in an individual in need of treatment for a disease caused by malignant cells of a first expression cassette comprising a tumor specific promoter operably linked to a nucleic acid sequence encoding a syncytium-inducing polypeptide, wherein said first expression cassette is flanked on either side by a site recognized by a recombinase; and
(b) a second expression cassette comprising a tissue-specific promoter operably linked to a nucleic acid sequence encoding said recombinase, wherein said tumor-specific promoter is active in said malignant cells, and said tissue specific promoter is active in non-malignant cells of the same lineage as the malignant cells, but substantially inactive in said malignant cells, wherein said expression results in a reduction in tumor size.
26. The method of claim 25, wherein said step of permitting expression comprises the step of administering first and second expression cassettes to an individual in need of treatment for a disease caused by malignant cells.
27. The method of claim 25, wherein said recombinase is cre recombinase and said site recognized by a recombinase is a loxp site.
28. The method of claim 25, wherein said tumor-specific promoter is selected from the group consisting of a carcino embryonic antigen promoter, an alphafetoprotein promoter, a tyrosinase promoter, an Erb-B2 promoter and a myelin basic protein promoter.
29. The method of claim 28, wherein said tumor specific promoter is the carcinoembryonic antigen promoter.
30. The method of claim 25, wherein said sequence which encodes a syncytium-inducing polypeptide encodes an FMG.
31. The method of claim 30, wherein FMG is a viral FMG.
32. The method of claim 31, wherein said viral FMG is selected from the group consisting of type G membrane glycoprotein of rabies virus, type G membrane glycoprotein of Mokola virus, type G membrane glycoprotein of vesicular stomatitis virus, type G membrane glycoprotein of Togaviruses, murine hepatitis virus JHM surface projection protein, porcine respiratory coronavirus spike glycoprotein, porcine respiratory coronavirus membrane glycoprotein, avian infectious bronchitis spike glycoprotein and its precursor, bovine enteric coronavirus spike protein, paramyxovirus SV5 F protein, Measles virus F protein, canine distemper virus F protein, Newcastle disease virus F protein, human parainfluenza virus 3 F protein, simian virus 41 F protein, Sendai virus F protein, human respiratory syncytial virus F protein, Measles virus hemagglutinin, simian virus 41 hemagglutinin neuraminidase proteins, human parainfluenza virus type 3 hemagglutinin neuraminidase, Newcastle disease virus hemagglutinin neuraminidase, human herpesvirus 1 gH, simian varicella virus gH, human herpesvirus gB proteins, bovine herpesvirus gB proteins, cercopithecine herpesvirus gB proteins, Friend murine leukemia virus envelope glycoprotein, Mason Pfizer monkey virus envelope glycoprotein, HIV envelpoe glycoprotein, influenza virus hemaglutinin, poxvirus membrane glycoproteins, mumps virus hemaglutinin neuraminidase, mumps virus glycoproteins F1 and F2, West Nile virus membrane glycoprotein, herpes simplex virus membrane glycoprotein, Russian Far East encephalitis virus membrane glycoprotein, Venezuelan equine encephalitis virus membrane glycoprotein and varicella virus membrane glycoprotein.
33. The method of claim 25, wherein said step of administering comprises administering one or more retroviral vectors comprising said first and second expression cassettes.
34. The method of claim 25, wherein said step of administering comprises administering a cell comprising said one or more recombinant nucleic acid vector.
35. An expression cassette system comprising:
(a) a first expression cassette comprising an hypoxic response element (HRE) operably linked to a nucleic acid sequence encoding a syncytium-inducing polypeptide, wherein said nucleic acid sequence encoding a syncytium-inducing polypeptide is flanked on either side by a sequence recognized by a recombinase;
(b) a second expression cassette comprising a tumor specific promoter operably linked to a nucleic acid sequence encoding a cytotoxic gene product; and
(c) a third expression cassette comprising a tumor specific promoter operably linked to said nucleic acid sequence encoding said recombinase.
36. An expression cassette system comprising:
(a) a first expression cassette comprising an hypoxic response element (HRE) operably linked to a nucleic acid sequence encoding a syncytium-inducing polypeptide, wherein said nucleic acid sequence encoding a syncytium-inducing polypeptide is flanked on either side by sequences recognized by a recombinase;
(b) a second expression cassette comprising a tumor specific promoter operably linked to a nucleic acid sequence encoding a cytokine; and
(c) a third expression cassette comprising a tumor specific promoter operably linked to said nucleic acid sequence encoding said recombinase.
37. The expression cassette system of claim 35 or 36, wherein said vector is a retroviral vector.
38. The expression cassette system of claim 35 or 36, wherein said tumor specific promoter is selected from the group consiting of a carcinoembryonic antigen promoter, an alphafetoprotein promoter, a tyrosinase promoter, an Erb-B2 promoter and a myelin basic protein promoter.
39. The expression cassette system of claim 38, wherein said tumor specific promoter is a carcinoembryonic antigen promoter.
40. The expression cassette system of claim 35, wherein said cytotoxic gene product is selected from the group consisting of HSV thymidine kinase, cytosine deaminase, nitroreductase, and a viral FMG.
41. The expression cassette system of claim 36, wherein said cytokine is selected from the group consisting of IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-12, GM-CSF, IFN- and TNF-.
42. A cell comprising an expression cassette system of claim 35 or 36.
43. The cell of claim 42, wherein said cell is a macrophage.
44. A method of reducing the size of a tumor in an individual said method comprising the step of permitting the expression in an individual of an expression cassette system comprising:
(a) a first expression cassette comprising a nucleic acid sequence encoding a syncytium-inducing polypeptide, operably linked to an hypoxic response element (HRE), wherein said nucleic acid sequence encoding a syncytium-inducing polypeptide is flanked on either side by sequences recognized by a recombinase,
(b) a second expression cassette comprising a nucleic acid sequence encoding a cytotoxic gene product, operably linked to a tumor specific promoter, and
(c) a third expression cassette comprising a nucleic acid sequence encoding said recombinase, operably linked to said tumor specific promoter, wherein expression of said expression cassette system reduces the size of a tumor.
45. The method of claim 46, wherein said step of permitting expression comprises introducing said expression cassette system to a macrophage and introducing said macrophage to said individual.
46. A method of reducing the size of a tumor in an individual said method comprising the step of permitting the expression in an individual of an expression cassette system comprising:
(a) a first expression cassette comprising a nucleic acid sequence encoding a syncytium-inducing polypeptide, operably linked to an hypoxic response element (HRE), wherein said nucleic acid sequence encoding a syncytium-inducing polypeptide is flanked on either side by sequences recognized by a recombinase,
(b) a second expression cassette comprising a nucleic acid sequence encoding a cytokine, operably linked to a tumor specific promoter, and
(c) a third expression cassette comprising a nucleic acid sequence encoding said recombinase, operably linked to said tumor specific promoter, wherein expression of said expression cassette system reduces the size of a tumor.
47. The method of claim 46, wherein said step of permitting expression comprises introducing said expression cassette system to a macrophage and introducing said macrophage to said individual.
48. A macrophage-tumor cell hybrid.
49. The macrophage-tumor cell hybrid of claim 48, wherein said hybrid comprises an expression cassette system of claims 35.
50. The macrophage-tumor cell hybrid of claim 48, wherein said hybrid comprises an expression cassette system of claims 36.
51. A cell-tumor cell hybrid, wherein said hybrid comprises a hypoxic transcription factor.
52. The cell-tumor cell hybrid of claim 51, wherein said hybrid an expression cassette system of claim 35.
53. The cell-tumor cell hybrid of claim 51, wherein said hybrid an expression cassette system of claim 36.