That which is claimed is:
1. A polypeptide that modulates programmed cell death, comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 8.
2. A composition comprising a polypeptide as of claim 1 an a pharmaceutically acceptable carrier thereof.
3. The polypeptide according to claim 1, wherein the amino acid sequence is SEQ ID NO: 2 or SEQ ID NO: 8.
4. An apoptotically active polypeptide having at least 60% amino acid identity over the complete amino acid sequence of SEQ ID NO: 1.
5. The polypeptide according to claim 4, wherein the polypeptide has a sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 8
6. A method for preventing or treating a disorder associated with a decrease in apoptosis, the method comprising:
administering to a subject in need of such treatment an effective amount of a pharmaceutical composition comprising a apoptotically active protein having an amino acid sequence (i) of SEQ ID NO: 1 or (ii) with at least 60% homology to SEQ ID NO: 1.
7. The method according to claim 6, wherein the homologous amino acid sequence (ii) is selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 8.
8. The method according to claim 7, wherein the homologous amino acid sequence is SEQ ID NO: 2.
9. A polynucleotide that encodes for a protein that modulates apoptosis, the polynucleotide comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 9.
10. An apoptotically active polynucleotide that hybridizes with at least one nucleotide sequence according to claim 9 under high stringency conditions.
11. An apoptotically active polynucleotide that has at least 90% homology to the nucleotide sequences of claim 9.
12. A method for detecting a polynucleotide encoding a protein having at least one amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 8 in a biological test sample containing nucleic acids, the method comprising the steps of:
(a) mixing at least a fragment of a complement of the polynucleotide sequence encoding at least a fragment of a protein having at least one amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 8 with the biological test sample containing nucleic acids, to form a resulting mixture;
(b) subjecting the mixture to conditions such that hybridization will occur between the biological test sample and the complement of the polynucleotide sequence encoding at least a fragment of a protein having at least one amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO:5 and SEQ ID NO: 8; and
(c) detecting hybridization complexes in the mixture subjected to hybridization conditions, wherein the presence of a hybridization complex correlates with the presence of a polynucleotide encoding a protein having at least one amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 8 in the biological test sample.
13. A method for screening a potential cellular apoptosis inhibiting compound for determining it utility as a therapeutic agent for treatment of diseases associated with increased programmed cell death, the method comprising:
(a) contacting a cell which expresses a protein including at least one amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQID NO: 3, SEQ ID NO: 4, SEQ ID NO:5 and SEQ ID NO: 8 with the test compound; and
(b) determining the level of apoptosis activity of the cell, wherein a decrease in activity identifies a compound that inhibits apoptotic activity.
14. An expression vector containing at least a fragment of a polynucleotide sequence, wherein the polynucleotide has a nucleotide sequence that encodes a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 8, or its compliment.
15. A transformed host cell containing an expression vector as in claim 14.
16. The transformed host cell according to claim 15, wherein the host cell has been cultured for expression of the polypeptide in recoverable form.
17. A purified antibody which binds to a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 8.
18. A method for preventing or treating a disorder associated with decreased apoptosis comprising:
(a) administering to a subject in need of such treatment a pharmaceutical composition comprising a polypeptide including at least one amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 8.
19. A vaccine comprising a polynucleotide sequence that encodes a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO:5 and SEQ ID NO: 8.
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. A handcuff for gripping a member comprising:
a first half-bracelet,
a second half-bracelet configured to close with the first half-bracelet around the member by pivoting around a first axis,
a locking mechanism including a sensor assembly configured to block opening of the first half-bracelet and the second half-bracelet in response to pressure from the member, and
an opening mechanism configured to open the first half-bracelet open relative to the second half-bracelet in the absence of the member applying pressure to the sensor.
2. A handcuff according to claim 1, wherein the first half-bracelet has a central part located around the first axis that includes a clasp having first teeth configured to engage with second teeth of an opening lever, the first and second teeth being maintained against each other by a pull-back spring.
3. A handcuff according to claim 2, wherein the opening lever is configured to release the teeth of the clasp while pivoting on a second axis against the action of the spring.
4. A handcuff according to claim 3, wherein the opening lever pivots around the second axis against the action of the spring by the action of an opening component.
5. A handcuff according to claim 3, wherein the opening lever pivots around the second axis and against the spring in response to movement of a key.
6. A handcuff according to claim 1, further comprising a wheel at the end of the second half-bracelet configured to roll around the member to be blocked and so preventing the second half-bracelet to get caught on clothing or skin.
7. A handcuff according to claim 1, wherein said handcuff of claim 1 is coupled to another handcuff by means of rigid, flexible or articulated connection.
8. A handcuff according to claim 1, wherein said opening mechanism includes a clutch, a blocking notch and a spring configured to allow the handcuff to remain open yet prevent unintended closing.
9. A handcuff according to claim 1, wherein said locking mechanism includes a manual closing element in the form of a trigger, said locking mechanism being configured to manually prevent unintended closing.
10. A handcuff according to claim 9, wherein said trigger is configured to be actuated by an operator’s finger.
11. A handcuff according to claim 1, wherein said locking mechanism includes a locking pawl and said first half-bracelet includes a notch into which the locking pawl is inserted against a return spring, whereby the first half-bracelet may be locked together in a closed position with the second half-bracelet.
12. A handcuff according to claim 11, wherein said opening mechanism includes a release lever configured to pivot around the first axis, said opening mechanism further including a notch configured to receive by a pin of said locking pawl under action of said return spring to maintain the lock in an open position whereby pressure from the member when disposed between the first and second half-bracelets displaces said release lever and turns said locking pawl around an axis to disengage said pin from said notch.
13. A handcuff according to claim 2, wherein said first half-bracelet includes an opening lever configured to be blocked by said opening mechanism while the first and second half-bracelets are locked in a closed position, the first half-bracelet having teeth configured to be retained against teeth of said opening lever under force applied by a return spring.
14. A handcuff according to claim 3, wherein said opening lever is configured to disengage the teeth of the first half-bracelet by turning against the action of a spring by means of a key received in a keyhole.