1. A method of treating an Hsp70 dependent cancer, comprising:
providing at least one Hsp70 dependent cancer cell;
contacting the at least one cell with a sub-effective concentration of a dihydropyrimindinone compound; and
contacting the at least one cell with a sub-effective concentration of a proteasome inhibitor, wherein the sub-effective concentration of the dihydropyrimidinone compound and the sub-effective concentration of the proteasome inhibitor have a synergistic effect upon the at least one cell.
2. The method of claim 1, further comprising the step of contacting the at least one cell with an Hsp90 inhibitor.
3. The method of claim 2, wherein the Hsp90 inhibitor further comprises 17-AAG.
4. The method of claim 1, wherein the Hsp70 dependent cancer is selected from the group consisting of: multiple myeloma, lung cancer, breast cancer, colon cancer, cervical cancer, and combinations thereof.
5. The method of claim 1, wherein providing at least one cell includes providing a plurality of Hsp70 dependent cancer cells.
6. The method of claim 1, wherein the dihydro pyrimidinone is one selected from the group consisting of: an Hsp70 inhibitor, a MAL3-101, a MAL3-101 derivative, and combinations thereof.
7. The method of claim 1, wherein the proteasome inhibitor includes MG-132.
8. The method of claim 1, wherein the sub-effective concentration of the dihydropyrimidinone is a therapeutically effective amount.
9. The method of claim 1, wherein the sub-effective concentration of the proteasome inhibitor is a therapeutically effective amount.
10. The method of claim 1, wherein the sub-effective concentration of the dihydropyrimidinone is from about 0.01 \u03bcM to about 0.1 \u03bcM.
11. The method of claim 1, wherein the sub-effective concentration of the proteasome inhibitor is from about 0.01 \u03bcM to about 0.1 \u03bcM.
12. A method of treating multiple myeloma, comprising:
providing a plurality of multiple myeloma cells,
co-administering a sub-effective concentration of each of a Hsp70 inhibitor and a proteasome inhibitor to the plurality of cells, wherein the subeffective concentrations of the Hsp70 inhibitor and the proteasome inhibitor together have a synergistic apoptotic effect on the multiple myeloma cells.
13. The method of claim 12, wherein the Hsp70 inhibitor includes a MAL3-101.
14. The method of claim 12, wherein the proteasome inhibitor comprises a Bortezomib.
15. The method of claim 12, further comprising the administration of an anti-oncogentic therapy, said anti-oncogenic therapy selected from the group consisting of: an Hsp90 inhibitor, a 17-AAG, a chemotherapy, a radiation therapy, and combinations thereof.
16. A method of treating multiple myeloma, comprising: co-administering to a microvasculature of a plurality of multiple myeloma cells a sub-effective concentration of an Hsp70 inhibitor and a sub-effective concentration of a proteasome inhibitor, wherein the Hsp70 inhibitor and the proteasome inhibitor have a synergistic effect on the microvasculature.
17. The method of claim 16, wherein the microvasculature further comprises a plurality of endothelial progenitor cells, which function to feed the plurality of multiple myeloma cells.
18. The method of claim 16, further wherein the synergistic effect is an apoptosis of a plurality of the microvasculature.
19. A combination therapy for a plurality of Hsp70 dependent cancer cells, comprising:
a sub-effective concentration of an Hsp70 inhibitor;
a sub-effective concentration of a proteasome inhibitor; and
a biologically compatible delivery means.
20. The combination therapy of claim 19, further wherein the Hsp70 dependent cancer cells are selected from the group consisting of: lung cancer cells, breast cancer cells, cervical cancer cells, multiple myeloma cells, and combinations thereof.
21. The combination therapy of claim 19, wherein the Hsp70 inhibitor further comprises a small molecule dihydropyrimidinone compound.
22. The combination therapy of claim 19, wherein the biologically compatible delivery means further comprises dimethyl sulfoxide (DMSO).
23. The combination therapy of claim 19, further wherein the sub-effective concentration of the dihydropyrimidinone further comprises a MAL3-101 in a concentration of about 0.01 \u03bcM to about 0.1 \u03bcM.
24. The combination therapy of claim 19, further wherein the sub-effective concentration of the proteasome inhibitor further comprises a MG-132 in a concentration of about 0.01 \u03bcM to about 0.1 \u03bcM.
25. A composition of matter, comprising:
an Hsp70 inhibitor; and
a proteasome inhibitor, each of the Hsp70 inhibitor and said proteasome inhibitor are in a pharmaceutically acceptable carrier, wherein the Hsp70 inhibitor and the proteasome inhibitor in the carrier are administrable to a plurality of Hsp70 dependent cancer cells.
26. The composition of claim 25, further comprising an Hsp90 inhibitor.
27. A method of screening Hsp70 inhibitors, comprising:
administering to at least one Hsp70 dependent cancer cell an amount of a candidate Hsp70 inhibitor; and
assaying said at least one cell to determine whether Hsp70 is inhibited.
28. The method of claim 27 further comprising the step of quantifying at least one result.
29. The method of claim 27, wherein the candidate Hsp70 inhibitor is an identified Hsp70 inhibitor upon exhibiting factors selected from the group consisting of: a slower Hsp70 dependent cancer cell growth, an apoptosis of Hsp70 dependent cancer cells, and a combination thereof.
30. The method of claim 27, further comprising the step of administering to the Hsp70 dependent cancer cell a proteasome inhibitor before the assaying step.
31. A method of diagnosing a progression of Hsp70 cancer, comprising:
providing a sample of Hsp70 dependent cancer cells from a subject;
assaying the sample to determine a quantity of secreted immunoglobulins;
correlating the quantity of secreted immunoglobulins to a standard.
32. The method of claim 31, wherein assaying the sample further comprises performing an Elisa test on the sample to determine a quantity of light chain immunoglobulins secreted from the Hsp70 dependent cells.
33. The method of 31, wherein correlating further comprises comparing the quantity of secreted immunoglobulins to a medical standard for various levels of multiple myeloma.
34. The method of claim 31, further comprising the step of assigning the subject a clinical course of multiple myeloma.
35. The method of claim 31, further comprising correlating the quantity of secreted immunoglobulins to determine a median survival of the subject.
36. A method for determining a therapy for a multiple myeloma patient in need thereof, comprising:
providing a sample of multiple myeloma cells from a subject;
assaying the sample to determine a quantity of secreted immunoglobulins;
correlating the quantity of secreted immunoglobulins to a standard; wherein each quantity is assigned to a level of multiple myeloma, wherein a high level correlates to an aggressive multiple myeloma, while a low level correlates to a less aggressive multiple myeloma.
37. The method of claim 36, further comprising selecting a therapy for the multiple myeloma which correlates to the level of the multiple myeloma.
38. The method of claim 37, further wherein the therapy is selected from the group consisting of: a chemotherapy, a radiation therapy, a hormone therapy, a proteasome therapy, an Hsp70 inhibitor therapy, an Hsp90 inhibitor therapy, a gene suppression therapy, and combinations 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 method for determining a yaw direction of a wind turbine comprising:
receiving at a component of the wind turbine a signal broadcasted from a source;
determining a direction from the component towards the source based on the received signal; and
determining the yaw direction of the wind turbine in relation to the determined direction towards the source.
2. The method according to claim 1, wherein the yaw direction is determined based on a Radio Direction Finding method.
3. The method according to claim 2, wherein the Radio Direction Finding method is based on a Pseudo-Doppler method.
4. The method according claim 1, wherein
the signal is received via an antenna andor receiver being attached to the component, the antenna andor receiver having a calibrated 0\xb0-direction in relation to a direction of the component;
an offset angle is determined based on the calibrated 0\xb0-direction in relation to the determined direction; and
the yaw direction is determined based on the offset angle and the determined direction.
5. The method according to claim 4, wherein
the signal is broadcasted from the source located at a source-specific geographic position;
the broadcasted signal is received at a component-specific geographic position;
a relative compass heading is derived by processing the component-specific geographic position and the source-specific geographic position; and
a yaw angle of the wind turbine is derived based
on the offset angle, and
on the relative compass heading.
6. The method according to claim 5, wherein the yaw angle is determined in relation towards a defined cardinal direction.
7. The method according to claim 1, wherein the broadcasted signal is received at a nacelle or rotor of the wind turbine.
8. The method according to claim 1, wherein
the yaw direction is determined
continuously,
periodically, or
within at least one defined time interval, or
one-time.
9. The method according to claim 1, wherein the geographic position is defined according to
a Geographic Latitude and Longitude coordinate system,
an Universal Transverse Mercator coordinate system, or
an Universal Polar Stereographic coordinate system.
10. A wind turbine, comprising:
a receiver for receiving a signal broadcasted from a source;
a processing unit that is arranged for:
determining a direction from the receiver towards the source based on the received signal, and
determining a yaw direction of the wind turbine in relation to the determined direction towards the source.
11. A device comprising andor being associated with a processor unit andor hard-wired circuit andor a logic device that is arranged such that the method according to claim 1 is executable thereon.
12. The device according to claim 11, wherein the device is a yaw encoder.
13. A computer program product directly loadable into a memory of a digital computer, comprising software code portions for performing the steps of the method according to claim 1.
14. A computer readable medium, having computer-executable instructions adapted to cause a computer system to perform the steps of the method according to claim 1.