Author: claimsbot

1. A resistance device for an exerciser with an external design thereof in a unitary machine; application of the present invention to an exerciser minimizes the volume thereof and obtains the effect of saving the most cost; the structure of the present invention mainly comprises external cases of left and right machines, a driving resistance disk, a positioning ring, a adjustable resistance disk, an oblique Y-shaped clamp, a tension spring, a main shaft and a drawing steel rope; wherein:
the external cases of left and right machines are locked in clamping type and filled with machine oil of high viscosity and a main shaft positioned and sealed through the cooperation of a shaft bearing and a oil seal to allow the driving resistance disk, the positioning ring, the adjustable resistance disk, the oblique Y-shaped clamp and the tension spring to exist and operate therein;
the driving resistance disk has a unitary belt wheel penetrated by the main shaft; the internal and external portions of the wheel are disposed with the shaft bearings and the oil seals; it is capable of making spinning rotation and forming a corresponding structure with the adjustable resistance disk; the front plane of the disk is disposed with a plurality of concentric circular pieces staggered and inserted with resistance pieces of the adjustable resistance disk; a proper gap is reserved between the resistance pieces; the innerest rims of the resistance pieces are disposed with circular oil lead holes and the resistance pieces are disposed with inclined and convergent slot ways; the backside of the disk is disposed with diagonal slot ways for rapidly leading the machine oil into all the resistance pieces;
the adjustable resistance disk is penetrated by the main shaft and controlled by the positioning ring, the oblique Y-shaped clamp and the tension spring; it is not capable of making spinning rotation; the front aspect of the disk is stopped and positioned by the positioning ring; the rear aspect thereof is forced by the tension spring to form a corresponding structure with the driving resistance disk; the front plane of the disk is disposed with a plurality of concentric circular pieces staggered and inserted with resistance pieces of the driving resistance disk; a proper gap is reserved between the resistance pieces; the innerest rims of the resistance pieces are disposed with circular oil lead holes and the resistance pieces are disposed with inclined and convergent slot ways; the backside of the disk is disposed with diagonal slot ways for rapidly leading the machine oil into all the resistance pieces;
the oblique Y-shaped clamp is inclined and slightly resilient; the hollow section at the bottom portion thereof straddles on the main shaft with two end foot portions respectively fastened on the backside of the adjustable resistance disk; the central position on the oblique Y-shaped clamp is fastened with the drawing steel rope penetrated into the external case of the machine; the top end point of the said oblique Y-shaped clamp is fixed onto the inner rim wall of the external case of the machine to draw the adjustable resistance disk via the drawing steel rope to form a micro adjusting function of displacing forwardly and backwardly.
2. A resistance device for an exerciser according to claim 1, wherein the oil lead slot ways disposed on the driving resistance disk and the adjustable resistance disk are not of a corresponding structure.
3. A resistance device for an exerciser according to claim 1, wherein the adjustable resistance disk can be a member of two semi-spheres covered externally onto the outer rim side of the driving resistance disk; the inner and outer rims of the resistance pieces of two disks are correspondingly staggered and inserted to enable the driving resistance disk to make spinning rotation under the applied external force and the adjustable resistance disk to have function of expanding displacement so as to achieve the equivalent effect of forming resistance and adjusting resistance value.

The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.

1-20. (Canceled)
21. A method of producing a transgenic mouse comprising a vector, comprising
a) introducing a vector into murine embryonic stem (ES) cells, wherein the vector comprises:
i) a 5 gene trap cassette, comprising in operable combination:
1) a splice acceptor;
2) a first exon sequence located 3 to said splice acceptor, said first exon sequence encoding a marker enabling the identification of a cell expressing said first exon sequence; and
3) a polyadenylation sequence located at the 3 end of said first exon sequence;

ii) a 3 gene trap cassette located 3 to said polyadenylation sequence, comprising in operable combination:
1) a first promoter;
2) a second exon sequence located 3 from and expressed by said first promoter, said second exon sequence not encoding an activity conferring antibiotic resistance;
3) a splice donor sequence located at the 3 end of said second exon sequence; and
wherein said vector does not encode a promoter mediating the expression of said first exon sequence, and wherein said vector does not encode a sequence that mediates the polyadenylation of an mRNA transcript encoded by said second exon sequence;
b) selecting a murine ES cell that comprises the vector; and
c) making a transgenic mouse comprising the vector from the selected murine ES cell that comprises the vector.
22. The method of claim 21, wherein the vector from the selected murine ES cell that comprises the vector is non-homologously incorporated into the genome of at least one cell in the transgenic mouse.
23. The method of claim 22, further comprising identifying at least one trapped cellular exon after (b).
24. The method of claim 22, further comprising identifying at least one trapped cellular exon after (c).
25. The method of claim 21, wherein the transgenic mouse comprising the vector is a somatic transgenic mouse.
26. The method of claim 21, wherein the transgenic mouse comprising the vector is a germ line transgenic mouse.
27. The method of claim 21, wherein the first exon sequence additionally encodes an internal ribosome entry site operatively positioned between said splice acceptor and an initiation codon of said first exon.
28. The method of claim 21, wherein the vector additionally comprises in the region between said polyadenylation sequence and said first promoter at least one of a transcription termination sequence, a 3 terminal exon, and a sequence encoding a self-cleaving RNA.
29. The method of claim 21, wherein the marker encoded by the first exon sequence of the vector is selected from a marker conferring antibiotic resistance, a marker conferring antibiotic sensitivity, an enzymatic marker, a recombinase, and a fluorescent marker.
30. The method of claim 29 wherein the marker confers neomycin resistance.
31. The method of claim 21, wherein the vector is selected from a viral vector and a retroviral vector.
32. The method of claim 23, wherein the identifying at least one trapped cellular exon comprises:
a) obtaining a chimeric transcript resulting from splicing of the second exon sequence to a third exon sequence, wherein the third exon sequence is from the genome of the ES cell;
b) reverse transcribing said chimeric transcript to produce a cDNA template; and
c) determining the polynucleotide sequence of the cDNA template.
33. The method of claim 24, wherein the identifying at least one trapped cellular exon comprises:
a) obtaining a chimeric transcript resulting from splicing of the second exon sequence to a third exon sequence, wherein the third exon sequence is from the genome of the transgenic mouse;
b) reverse transcribing said chimeric transcript to produce a cDNA template; and
c) determining the polynucleotide sequence of the cDNA template.
34. A method of making a transgenic mouse comprising a vector, comprising
a) introducing a vector into murine embryonic stem (ES) cells, wherein the vector comprises a 3 gene trap cassette, comprising in operable combination:
i) a promoter;
ii) an exon sequence located 3 from and expressed by said first promoter, said exon sequence not encoding an activity conferring antibiotic resistance; and
iii) a splice donor sequence located at the 3 end of said exon sequence;

wherein the vector does not encode a sequence that mediates the polyadenylation of an mRNA transcript encoded by said exon sequence;
b) selecting a murine ES cell that comprises the vector; and
c) making a transgenic mouse comprising the vector from the selected murine ES cell that comprises the vector.
35. The method of claim 34, wherein the vector from the selected murine ES cell that comprises the vector is non-homologously incorporated into the genome of at least one cell in the transgenic mouse.
36. The method of claim 35, further comprising identifying at least one trapped cellular exon after (b).
37. The method of claim 35, further comprising identifying at least one trapped cellular exon after (c).
38. The method of claim 34, wherein the transgenic mouse comprising the vector is a somatic transgenic mouse.
39. The method of claim 34, wherein the transgenic mouse comprising the vector is a germ line transgenic mouse.
40. The method of claim 34, wherein the exon sequence additionally encodes an internal ribosome entry site operatively positioned between said splice acceptor and an initiation codon of said exon sequence.
41. The method of claim 34, wherein the vector additionally comprises in the region between said polyadenylation sequence and said promoter at least one of a transcription termination sequence, a 3 terminal exon, and a sequence encoding a self-cleaving RNA.
42. The method of claim 34, wherein the exon sequence encodes a marker selected from an enzymatic marker, a recombinase, and a fluorescent marker.
43. The method of claim 42 wherein the marker is a fluorescent marker.
44. The method of claim 34, wherein the vector is selected from a viral vector and a retroviral vector.
45. The method of claim 36, wherein the identifying at least one trapped cellular exon comprises:
a) obtaining a chimeric transcript resulting from splicing of the exon sequence from the vector to a second exon sequence, wherein the second exon sequence is from the genome of the ES cell;
b) reverse transcribing said chimeric transcript to produce a cDNA template; and
c) determining the polynucleotide sequence of the cDNA template.
46. The method of claim 37, wherein the identifying at least one trapped cellular exon comprises:
a) obtaining a chimeric transcript resulting from splicing of the exon sequence from the vector to a second exon sequence, wherein the second exon sequence is from the genome of the transgenic mouse;
b) reverse transcribing said chimeric transcript to produce a cDNA template; and
c) determining the polynucleotide sequence of the cDNA template.

1. A method of inducing an immune response against malaria in a mammal, which method comprises intramuscularly administering to a mammal a composition comprising a pharmaceutically acceptable carrier and either or both of:
(a) about 1\xd7106 particle units (pu) to about 1\xd71012 pu of a first adenoviral vector comprising an adenoviral genome comprising a left inverted terminal repeat (ITR), the E2A region, the E2B region, late regions L1-LS, and a right ITR, and a nucleic acid sequence encoding a P. falciparum circumsporozoite protein (CSP) operably linked to a human CMV promoter, and
(b) about 1\xd7106 particle units pu to about 1\xd71012 pu of a second adenoviral vector comprising an adenoviral genome comprising a left inverted terminal repeat (ITR), the E2A region, the E2B region, late regions L1-LS, and a right ITR, and a nucleic acid sequence encoding a P. falciparum apical membrane antigen 1 (AMA-1) antigen operably linked to a human CMV promoter,
wherein the composition is administered to the mammal one or more times, and wherein the nucleic acid sequence encoding a P. falciparum CSP andor the nucleic acid sequence encoding a P. falciparum AMA-1 are expressed to produce the CSP andor the AMA-1 in the mammal to induce an immune response against malaria.
2. The method of claim 1, wherein the composition comprises the first adenoviral vector and the second adenoviral vector.
3. The method of claim 2, wherein the composition comprises about 5\xd7109 pu to about 5\xd71010 pu of the first adenoviral vector and about 5\xd7109 pu to about 5\xd71010 pu of the second adenoviral vector.
4. The method of claim 3, wherein the composition comprises about 1\xd71010 pu of the first adenoviral vector and about 1\xd71010 pu of the second adenoviral vector.
5. The method of claim 2, wherein the composition comprises about 1\xd71010 pu to about 1\xd71011 pu of the first adenoviral vector and about 1\xd71010 pu to about 1\xd71011 pu of the second adenoviral vector.
6. The method of claim 5, wherein the composition comprises about 5\xd71010 pu of the first adenoviral and about 5\xd71010 pu of the second adenoviral vector.
7. The method of claim 1, wherein the composition comprises the first adenoviral vector and does not comprise the second adenoviral vector.
8. The method of claim 7, wherein the composition comprises about 1\xd71010 pu to about 1\xd71011 pu of the first adenoviral vector.
9. The method of claim 8, wherein the composition comprises about 5\xd71010 pu of the first adenoviral vector.
10. The method of claim 1, wherein the composition comprises the second adenoviral vector and does not comprise the first adenoviral vector.
11. The method of claim 10, wherein the composition comprises about 1\xd71010 pu to about 1\xd71011 pu of the second adenoviral vector.
12. The method of claim 11, wherein the composition comprises about 5\xd71010 pu of the second adenoviral vector.
13. The method of claim 1, wherein each of the first and second adenoviral vectors is replication-deficient and requires complementation of both the E1 region and the E4 region of the adenoviral genome for propagation.
14. The method of claim 13, wherein the adenoviral genome of each of the first and second adenoviral vectors lacks the entire E1 region and at least a portion of the E4 region of the adenoviral genome.
15. The method of claim 14, wherein the nucleic acid sequence encoding P. falciparum CSP is inserted into the deleted E1 region of the adenoviral genome of the first adenoviral vector.
16. The method of claim 15, wherein the nucleic acid sequence encoding the P. falciparum AMA-1 antigen is inserted into the deleted E1 region of the adenoviral genome of the second adenoviral vector.
17. The method of claim 1, wherein P. falciparum CSP comprises codons expressed more frequently in mammals than in Plasmodium.
18. The method of claim 17, wherein the nucleic acid sequence encoding P. falciparum CSP comprises SEQ ID NO: I0.
19. The method of claim 1, wherein the P. falciparum AMA-1 antigen comprises codons expressed more frequently in mammals than in Plasmodium.
20. The method of claim 19, wherein the nucleic acid sequence encoding P. falciparum AMA-1 antigen comprises SEQ ID NO: 16.
21. The method of claim 1, wherein the first adenoviral vector and the second adenoviral vector are the same.
22. The method of claim 1, wherein the mammal is a human.
23. The method of claim 1, wherein the composition is administered to the mammal once.
24. The method of claim 1, any of claims 1-23, wherein the composition is administered to the mammal twice.
25. The method of claim 1, wherein the method further comprises administering a boosting composition to the mammal, wherein the boosting composition comprises a P. falciparum circumsporozoite protein (CSP), or an immunogenic portion thereof, andor a P. falciparum apical membrane antigen 1 (AMA-1) antigen, or an immunogenic portion thereof.
26. The method of claim 25, wherein the boosting composition is administered to the mammal at least 10 days after administration of the composition comprising the first andor second adenoviral vectors.
27. The method of claim 25, wherein the boosting composition is administered to the mammal four months after administration of the composition comprising the first andor second adenoviral vectors.
28. The method of claim 1, wherein the method further comprises administering a priming composition to the mammal, wherein the priming composition comprises a plasmid encoding a P. falciparum circumsporozoite protein (CSP), or an immunogenic portion thereof, andor a P. falciparum apical membrane antigen 1 (AMA-1) antigen, or an immunogenic portion thereof.
29. The method of claim 1, wherein the method further comprises administering a priming composition to the mammal, wherein the priming composition comprises a viral vector encoding a P. falciparum circumsporozoite protein (CSP), or an immunogenic portion thereof, andor a P. falciparum apical membrane antigen 1 (AMA-1) antigen, or an immunogenic portion thereof.
30. The method of claim 28, wherein the priming composition is administered to the mammal at least 10 days before administration of the composition comprising the first andor second adenoviral vectors.
31. The method of claim 29, wherein the priming composition is administered to the mammal four months before administration of the composition comprising the first andor second adenoviral vectors.
32. The method of claim 29, wherein the priming composition is administered to the mammal at least 10 days before administration of the composition comprising the first andor second adenoviral vectors.
33. The method of claim 29, wherein the priming composition is administered to the mammal four months before administration of the composition comprising the first andor second adenoviral vectors.

The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.

1. An apparatus for adjusting the speed of an engine, said apparatus comprising:
an actuator operably connected to a shaft having an axis and a distal end, said actuator being adapted to displace said shaft along said axis;
a bracket comprising a first bracket end adapted to operably connect to a throttle cable and an opposing second bracket end attached to said actuator such that said shaft extends generally toward said first bracket end;
said shaft further comprising a coupling operably connected to said shaft and adapted to connect to a throttle plate such that said displacement of said shaft moves said coupling, thereby moving said throttle plate without substantially moving said bracket; whereby
adjustment of said throttle cable moves said bracket, thereby causing said coupling to move said throttle plate, and actuation of said actuator causes said shaft to move said coupling thereby moving said throttle plate without substantially moving said bracket.
2. The apparatus according to claim 1, further comprising
a controller adapted to receive a signal corresponding to the operating speed of said engine and to control the actuation of said actuator whereby said controller causes said actuator to move said throttle plate automatically in response to said signal.
3. The apparatus according to claim 2, further comprising
a controller interface comprising a power switch and a display;
said power switch being adapted to activate and deactivate said controller and said display;
said display being electrically connected to said controller.
4. The apparatus of claim 1 wherein said actuator is a piezoelectric actuator.
5. The apparatus of claim 1 wherein said actuator comprises an electric motor.
6. The apparatus of claim 5 wherein said electric motor is a rotary stepper motor.
7. The apparatus of claim 5 wherein said electric motor comprises a diaphragm motor.
8. The apparatus of claim 1 wherein said actuator comprises a voice coil.
9. The apparatus of claim 1 wherein said actuator comprises a hydraulic cylinder.
10. The apparatus of claim 1 wherein said actuator comprises a pneumatic cylinder.
11. The apparatus of claim 1 wherein said bracket further comprises an aperture and at least a portion of said coupling extends through said aperture.
12. A system for synchronizing the rotational speeds of a plurality of engines of a vehicle, the system comprising:
a master engine and at least one slave engine;
an actuator assembly connected to said at least one slave engine, said actuator assembly comprising an actuator operably connected to a shaft having an axis and a distal end, said actuator being adapted to displace said shaft along said axis;
a bracket comprising a first bracket end adapted to operably connect to a throttle cable and an opposing second bracket end attached to said actuator such that said shaft extends generally toward said first bracket end;
said shaft further comprising a coupling operably connected to said shaft and adapted to connect to throttle plate operably connected to said slave engine such that said displacement of said shaft moves said coupling, thereby moving said throttle plate without substantially moving said bracket;
a master engine sensor capable of generating a signal corresponding to the rotational speed of said master engine;
a slave engine sensor capable of generating a signal corresponding to the rotational speed of said at least one slave engine;
a controller adapted to compare said signal corresponding to the rotational speed of said master engine and said signal corresponding to the rotational speed of said slave engine, and to cause said actuator to adjust said throttle plate of said slave engine to reduce said difference
whereby the rotational speed of said slave engine is synchronized to the rotational speed of said master engine.
13. The system of claim 12 wherein said controller is adapted to cause said actuator to adjust said throttle plate of said slave engine when said rotational speed of said master engine is within a predetermined range and said difference is less than a predetermined upper limit.
14. The system of claim 12 wherein further comprising
a plurality of slave engines, each said slave engine having a sensor capable of generating a signal corresponding to the rotational speed of said slave engine;
each said slave engine having an actuator assembly attached to said slave engine, said actuator assembly comprising an actuator operably connected to a shaft having an axis and a distal end, said actuator being adapted to displace said shaft along said axis;
a bracket comprising a first bracket end adapted to operably connect to a throttle cable and an opposing second bracket end attached to said actuator such that said shaft extends generally toward said first bracket end;
said shaft further comprising a coupling operably connected to said shaft and adapted to connect to the throttle plate of said slave engine such that said displacement of said shaft moves said coupling, thereby moving said throttle plate without substantially moving said bracket;
and wherein said controller is adapted to compare said signal corresponding to the rotational speed of said master engine and each said signal corresponding to the rotational speed of each of said slave engines, and to cause said actuator assembly attached to each said slave engine to adjust said throttle plate of said slave engine to reduce said difference
whereby the rotational speed of each said slave engine is synchronized to the rotational speed of said master engine.
15. The system of claim 12, further comprising
a controller interface comprising a power switch and a display;
said power switch being adapted to activate and deactivate said controller and said display;
said display being electrically connected to said controller.
16. The system of claim 12 wherein said actuator is a piezoelectric actuator.
17. The system of claim 12 wherein said actuator comprises an electric motor.
18. The system of claim 12 wherein said actuator comprises a hydraulic cylinder.
19. The system of claim 12 wherein said actuator comprises a pneumatic cylinder.
20. The system of claim 12 wherein said bracket further comprises an aperture and at least a portion of said coupling extends through said aperture.
21. An apparatus for adjusting the speed of an engine, said apparatus comprising:
an actuator operably connected to a shaft, said actuator being adapted to displace said shaft;
a first bracket comprising a first bracket end adapted to operably connect to a throttle cable and an opposing second bracket end attached to said shaft;
a second bracket assembly connected to said actuator and comprising a coupling adapted to connect to a throttle plate such that displacement of said shaft causes said actuator to move, thereby moving said second bracket assembly and said throttle plate without substantially moving said first bracket; whereby
adjustment of said throttle cable moves said first bracket, said shaft and said actuator, thereby causing said coupling to move said throttle plate, and actuation of said actuator causes said actuator to move said coupling.