1. A method for treating andor decreasing susceptibility to a protein aggregation disorder, in a subject in need thereof, comprising administering to said subject a protocol comprising pharmaceutically effective amount of
a peptidase capable of cleaving a polyQ peptide comprising at least 45 glutamine residues or a functional catalytic domain thereof, or
a nucleic acid sequence encoding said peptidase or functional catalytic domain, or
a compound capable of enhancing the expression, amount andor peptidase activity of said peptidase.
2. The method of claim 1, wherein said disorder is selected from Huntington’s disease, Dentatorubral-pallidoluysian atrophy (DRPLA), X-linked spinal and bulbar muscular atrophy (SBMA) and spinocerebellar ataxias (SCA).
3. A method for counteracting andor preventing aggregation of a polyQ protein in a cell, comprising providing said cell with a protocol comprising
a peptidase capable of cleaving a polyQ peptide comprising at least 45 glutamine residues or a functional catalytic domain thereof, or
a nucleic acid sequence encoding said peptidase or functional catalytic domain, or
a compound capable of enhancing the expression, amount andor peptidase activity of said peptidase.
4. The method of claim 3, wherein said protocol results in enhanced recovery of said polyQ protein.
5. A method to identify a candidate compound that counteracts protein aggregation,
the method comprising determining whether said candidate compound is capable of increasing the expression, amount andor peptidase activity of a peptidase that cleaves a polyQ peptide comprising at least 45 glutamine residues,
wherein a compound that is capable of increasing the expression, amount andor peptidase activity of said peptidase is identified as a compound that counteracts protein aggregation.
6. (canceled)
7. The method of any one of claim 1, 3 or 5, wherein said peptidase is a cysteine peptidase or a serine peptidase.
8. The method of any one of claim 1, 3 or 5, wherein said peptidase is TriPeptidyl Peptidase II (TPPII).
9. (canceled)
10. The method of claim 1 or 3, wherein said protocol comprises a combination of:
(a) a peptidase capable of cleaving a polyQ peptide comprising at least 45 glutamine residues or a functional catalytic domain thereof, or
a nucleic acid sequence encoding said peptidase or functional catalytic domain, or
a compound capable of enhancing the expression, amount andor peptidase activity of said peptidase; and
(b) a DnaJ heat shock protein or a functional protein aggregation inhibiting part thereof, or
a nucleic acid sequence encoding a DnaJ heat shock protein or a functional protein aggregation inhibiting part thereof, or
a compound capable of enhancing the expression, amount andor protein aggregation inhibiting activity of a DnaJ heat shock protein.
11. (canceled)
12. A pharmaceutical composition comprising:
(a) a peptidase capable of cleaving a polyQ peptide comprising at least 45 glutamine residues or a functional catalytic domain thereof, andor
a nucleic acid sequence encoding said peptidase or functional catalytic domain, andor
a compound capable of enhancing the expression, amount andor peptidase activity of said peptidase; and
(b) a DnaJ heat shock protein or a functional protein aggregation inhibiting part thereof, or
a nucleic acid sequence encoding a DnaJ heat shock protein or a functional protein aggregation inhibiting part thereof, or
a compound capable of enhancing the expression, amount andor protein aggregation inhibiting activity of a DnaJ heat shock protein;
and, optionally, a pharmaceutical acceptable carrier, diluent or excipient.
13. The composition of claim 12, wherein said DnaJ heat shock protein comprises DnaJB6 andor DnaJB8.
14. The composition of claim 12, wherein said compound capable of enhancing the protein aggregation inhibiting activity of said DnaJ heat shock protein comprises histone deacetylase 4 (HDAC 4) or a functional catalytic domain thereof or a nucleic acid sequence encoding HDAC 4 or a functional catalytic domain thereof.
15. A ubiquitin-polyQ fusion construct consisting of ubiquitin and a polyQ peptide, wherein said polyQ peptide consists of glutamine residues.
16. The fusion construct of claim 15, wherein said polyQ peptide has a length of at least 10 glutamine residues.
17. The fusion construct of claim 15, wherein said ubiquitin is linked to a detectable moiety.
18. The fusion construct of claim 17 which is a GFP-Ub-polyQ construct.
19. A nucleic acid sequence encoding the fusion construct of claim 15.
20. The method of claim 5 which employs the fusion construct of claim 15.
21. The method of claim 5 which employs the nucleic acid of claim 19.
22. The method of claim 10, wherein said DnaJ heat shock protein comprises DnaJB6 andor DnaJB8.
23. The method of claim 10, wherein said compound capable of enhancing the protein aggregation inhibiting activity of said DnaJ heat shock protein comprises histone deacetylase 4 (HDAC 4) or a functional catalytic domain thereof or a nucleic acid sequence encoding HDAC 4 or a functional catalytic domain 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.
1. A workflow management system for managing a workflow including a plurality of tasks, the workflow management system comprising:
a task data memory that stores task data;
a task control part that obtains task data from the task data storing part, calculating an index from the task data, and outputting an evaluation of the workflow based on the result of the calculation; and
a processor that executes the task control part, wherein
the task control part outputs a first warning prompting a user to modify the task when the index is greater than a first threshold and outputs a second warning prompting the user to modify the task when the index is greater than a second threshold,
the task control part includes a determining part that determines whether or not a person requesting the result of the calculation is in charge of the tasks,
when the determining part determines that the person requesting the result of the calculation is in charge of the tasks, the task control part outputs the result of the calculation and one of the first and second warnings for prompting the person to modify the tasks, and
when the determining part determines that the person requesting the result of the calculation is not in charge of the tasks, the task control part outputs only the result of the calculation.
2. The workflow management system as claimed in claim 1, wherein the task control part calculates discrepancy of plans based on the number of days required for completing the tasks included in the task data or the actual number of days and outputs evaluation of the workflow using the discrepancy as a performance evaluation index.
3. The workflow management system as claimed in claim 2, wherein the first threshold is 5% of the task period selected by a user, and the second threshold is 10% of the task period.
4. The workflow management system as claimed in claim 1, wherein the task control part calculates delay of plans based on the number of days required for completing the tasks included in the task data or the actual number of days and outputs evaluation of the workflow using the delay as a performance evaluation index.
5. The workflow management system as claimed in claim 4, wherein the first threshold is 5% of the task period selected by a user, and the second threshold is 10% of the task period.
6. The workflow management system as claimed in claim 5, wherein the task control part calculates the index from the task data corresponding to a part of or all of the tasks included in the workflow and outputs an evaluation of a part of or all of the workflow based on the result of the calculation.
7. A workflow management system for managing a workflow including a plurality of tasks, the workflow management system comprising:
a task data memory that stores task data;
a task control part that obtains task data from the task data storing part, calculates an index from the task data, and outputs an evaluation of the workflow based on the result of the calculation; and
a processor that executes the task control part, wherein
the task control part refers to the number of days for a plurality of members in charge of the tasks included in the task data to complete the tasks in a future predetermined period, calculates the total of the number of days required for each of the plural members to complete the tasks that they are in charge of, and outputs evaluation of the workflow by using the proportion of the total number of days required for completing the tasks in the future predetermined period as a performance evaluation index.
8. The workflow management system as claimed in claim 7, wherein the task control part outputs a warning when the proportion of the total number of days required for a member to complete the tasks in the future predetermined period is greater than a threshold.
9. The workflow management system as claimed in claim 7, wherein when the proportion of the total number of days required for a first member to complete the tasks in the future predetermined period is greater than a first threshold, a second member is output as a destination for transferring the tasks, wherein the proportion of the total number of days required for the second member to complete the tasks in the future predetermined period is no greater than a second threshold.
10. A workflow management system for managing a workflow including a plurality of tasks, the workflow management system comprising:
a task data memory that stores task data;
a task control part that obtains task data from the task data storing part, calculates an index from the task data, and outputs an evaluation of the workflow based on the result of the calculation; and
a processor that executes the task control part, wherein
the task control part outputs an evaluation of the workflow based on the total number of days required for completing the tasks included in the workflow and a future predetermined period calculated from the number of members in charge of the tasks and the average working hours of the members.
11. The workflow management system as claimed in claim 1, wherein the tasks can be designated according to a parent-child relationship or a sequential relationship with respect to other tasks.
12. A workflow management method, implemented by a processor of a computer, for managing a workflow including a plurality of tasks, the workflow management method comprising the steps of:
obtaining task data stored in a task data memory;
calculating, with the processor, an index from the obtained task data;
outputting an evaluation of the workflow based on the result of the calculation;
determining if a person requesting the result of the calculation is in charge of the tasks;
outputting, when the person requesting the result of the calculation is in charge of the task, a first warning prompting a user to modify the task if the index is greater than a first threshold, and outputting a second warning prompting the user to modify the task if the index is greater than a second threshold; and
outputting, when the person requesting the result of the calculation is not in charge of the task, only the result of the calculation.
13. The workflow management method as claimed in claim 12, wherein
the calculating includes calculating discrepancy of plans based on the number of days required for completing the tasks included in the task data or the actual number of days, and
the outputting includes outputting evaluation of the workflow using the discrepancy as a performance evaluation index.
14. The workflow management method as claimed in claim 13, wherein the first threshold is 5% of the task period selected by a user, and the second threshold is 10% of the task period.
15. The workflow management method as claimed in claim 12, wherein
the calculating includes calculating delay of plans based on the number of days required for completing the tasks included in the task data or the actual number of days, and
the outputting includes outputting evaluation of the workflow using the delay as a performance evaluation index.
16. The workflow management method as claimed in claim 15, wherein the first threshold is 5% of the task period selected by a user, and the second threshold is 10% of the task period.
17. The workflow management method as claimed in claim 12, wherein
the calculating includes calculating the index from the task data corresponding to a part of or all of the tasks included in the workflow, and
the outputting includes outputting an evaluation of a part of or all of the workflow based on the result of the calculation.
18. A workflow management method implemented by a processor of a computer, comprising:
obtaining task data stored in a task data memory;
calculating, with the processor, an index from the obtained task data; and
outputting an evaluation of the workflow based on the result of the calculation, wherein
the calculating includes referring to the number of days for a plurality of members in charge of the tasks included in the task data to complete the tasks in a future predetermined period and calculating the total of the number of days required for each of the plural members to complete the tasks that they are in charge of, and
the outputting includes outputting evaluation of the workflow by using the proportion of the total number of days required for completing the tasks in the future predetermined period as a performance evaluation index.
19. The workflow management method as claimed in claim 18, wherein the outputting includes outputting a warning when the proportion of the total number of days required for a member to complete the tasks in the future predetermined period is greater than a threshold.
20. A workflow management method, implemented by a processor of a computer, comprising:
obtaining task data stored in a task data memory;
calculating, with the processor, an index from the obtained task data; and
outputting an evaluation of the workflow based on the result of the calculation, wherein
when the proportion of the total number of days required for a first member to complete the tasks in a future predetermined period is greater than a first threshold, the outputting includes outputting a second member as a destination for transferring the tasks, wherein the proportion of the total number of days required for the second member to complete the tasks in the future predetermined period is no greater than a second threshold.