1. An apparatus for generating a mosaic picture of an object plane, comprising:
a capturing device for portion-by-portion capturing of the object plane at a two-dimensional distribution of capturing positions by sequentially moving to the capturing positions along a capturing path using a motor, so as to acquire subimages which represent pictures of portions of the object plane which overlap, while allocating the capturing positions to the subimages, the capturing positions allocated to the subimages deviate from actual capturing positions in accordance with inaccuracies of the motor; and
a processor for determining offset vectors between pairs of overlapping subimages by a similarity analysis of the overlapping subimages and for solving an optimization problem for finding an optimum set of capturing position variables for the subimages for minimizing a measure of a deviation between the offset vectors of the pairs of overlapping subimages and differences of the capturing position variables of the pairs of overlapping subimages, while complying with a secondary constraint for the capturing position variables which depends on error statistics statistically describing a distribution of a deviation between offsets between pairs of capturing positions allocated to the subimages, to which the motor moves immediately following each other, and actual offsets between corresponding pairs of actual capturing positions,
wherein the secondary constraint limits, in dependence on the error statistics, the difference of capturing position variables for pairs of subimages which immediately follow one another along the capturing path.
2. The apparatus as claimed in claim 1, wherein:
the two-dimensional distribution of capturing positions are substantially regularly arranged in rows and columns, and the capturing path is a zigzag path sequentially cycling through the two-dimensional distribution in rows of capturing positions, with traversing the rows of capturing positions sequentially along an advance direction aligned to the columns of capturing positions and alternatingly along a respective one of a first direction, a second direction, and the advance direction, so that capturing positions of subimages which immediately follow one another in accordance with the zigzag path are located, in relation to one another, along a respective one of the first direction, the second direction, and the advance direction, the error statistics being discriminative for the first direction, the second direction, and the advance direction, and
the secondary constraint for the differences of capturing position variables is different, in accordance with the error statistics, for pairs of subimages whose allocated capturing positions are located, in relation to one another, along the first direction, for pairs of subimages whose allocated capturing positions are located, in relation to one another, along the second direction, and for pairs of subimages whose allocated capturing positions are located, in relation to one another, along the advance direction.
3. The apparatus as claimed in claim 1, wherein the processor solves, as the optimization problem, the quadratic optimization problem
arg
\u2062
\u2062
min
p
\u2062
(
\uf605
W
\u2061
(
Ap
–
t
)
\uf606
2
)
\u2062
with the secondary constraint
Cp\u2266b,
wherein
p is a vector with 2\xd7N components which correspond to the capturing position variables of the N subimages in a pairwise manner;
t is a vector with 2\xd7M components which correspond to the M offset vectors in a pairwise manner;
A is a matrix with 2\xd7M rows and 2\xd7N columns, each of the rows comprising 2\xd7N\u22122zeros and a one and a minus one at column positions in each case which correspond to the subimages between which that offset vector is determined which in the vector t corresponds to the component pair corresponding to the respective row;
W is a matrix with 2\xd7M rows and 2\xd7M columns;
C is a matrix with 2\xd7N columns, each of the rows comprising 2\xd7N\u22122 zeros and a one and a minus one at column positions in each case which correspond to the subimages which immediately follow each other along the capturing path; and
b is a vector whose components depend on the error statistics.
4. The apparatus as claimed in claim 3, wherein W is a diagonal matrix whose diagonal components Wii in the respective row i of the matrix W correspond to a measure of a similarity of the subimages between which the offset vector at the corresponding component of the vector t is determined, in an overlap area of same as is defined by this very offset vector.
5. The apparatus as claimed in claim 1, wherein the processor determines the error statistics by computing statistical measures of a distribution of the deviation between the offset vectors of the pairs of overlapping subimages and differences of the capturing positions of the pairs of overlapping subimages.
6. The apparatus as claimed in claim 1, wherein the processor determines the error statistics by computing a central tendency and a dispersion of the deviations between the offset vectors of the pairs of overlapping subimages and differences of the capturing positions of the pairs of overlapping subimages.
7. The apparatus as claimed in claim 1, wherein the two-dimensional distribution of capturing positions essentially corresponds to a regular two-dimensional distribution in columns and rows.
8. The apparatus as claimed in claim 1, wherein the measure of the deviation is weighted with a measure of a similarity of the overlapping subareas for which the offset vectors are determined in each case.
9. The apparatus as claimed in claim 1, wherein the capturing device comprises:
an image sensor;
optical device for imaging a field-of-view portion of the object plane onto the image sensor;
the motor; and
a controller for controlling the motor and the image sensor, so that the object plane is captured at the two-dimensional distribution of capturing points; wherein
the motor effects a lateral relative motion between the object plane, and the image sensor and the optical device.
10. The apparatus as claimed in claim 9, wherein:
the controller:
dictates target capturing positions to the motor,
allocates the target capturing positions to the subimages as the capturing positions, and
instructs the image sensor, upon a confirmation signal for confirming that the target positions have been reached by the motor, to generate a respective subimage, and
the motor regulates a relative lateral location between the object plane, and the image sensor and the optical device, for such time until the target capturing positions have been reached, and to then send the confirmation signal to the controller in each case.
11. The apparatus as claimed in claim 9, wherein the optical device includes a microscope objective, and a relative motion generator includes the motor and a positioning table for displacing a slide which defines the object plane.
12. The apparatus as claimed in claim 9, wherein:
the controller:
dictates to the motor a capturing path,
instructs the image sensor at capturing times to generate a respective subimage, and
instructs the motor to detect a momentary relative location position which is allocated, as the capturing position, to the subimage generated at the respective capturing time, and
the motor changes the relative location position between the object plane and the image sensor and the optical device, in accordance with the capturing path and to detect the momentary relative location position upon the instruction from the controller.
13. A method of generating a mosaic picture of an object plane, comprising:
portion-by-portion capturing of the object plane at a two-dimensional distribution of capturing positions by sequentially moving to the capturing positions along a capturing path using a motor, so as to acquire subimages which represent pictures of portions of the object plane which overlap, while allocating the capturing positions to the subimages, the capturing positions allocated to the subimages deviate from actual capturing positions in accordance with inaccuracies of the motor; and
determining offset vectors between pairs of overlapping subimages by a similarity analysis of the overlapping subimages; and
solving an optimization problem for finding an optimum set of capturing position variables for the subimages for minimizing a measure of a deviation between the offset vectors of the pairs of overlapping subimages and differences of the capturing position variables of the pairs of overlapping subimages, while complying with a secondary constraint for the capturing position variables which depends on error statistics statistically describing a distribution of a deviation between offsets between pairs of capturing positions allocated to the subimages, to which the motor moves immediately following each other, and actual offsets between corresponding pairs of actual capturing positions,
wherein the portion-by-portion capturing is performed such that the secondary constraint limits, in dependence on the error statistics, the difference of capturing position variables for pairs of subimages which immediately follow one another along the capturing path.
14. A non-transitory computer readable medium including a computer program comprising a program code for performing, when the program runs on a computer, the method of generating a mosaic picture of an object plane, said method comprising:
portion-by-portion capturing of the object plane at a two-dimensional distribution of capturing positions by sequentially moving to the capturing positions along a capturing path using a motor, so as to acquire subimages which represent pictures of portions of the object plane which overlap, while allocating the capturing positions to the subimages, the capturing positions allocated to the subimages deviate from actual capturing positions in accordance with inaccuracies of the motor; and
determining offset vectors between pairs of overlapping subimages by a similarity analysis of the overlapping subimages; and
solving an optimization problem for finding an optimum set of capturing position variables for the subimages for minimizing a measure of a deviation between the offset vectors of the pairs of overlapping subimages and differences of the capturing position variables of the pairs of overlapping subimages, while complying with a secondary constraint for the capturing position variables which depends on error statistics statistically describing a distribution of a deviation between offsets between pairs of capturing positions allocated to the subimages, to which the motor moves immediately following each other, and actual offsets between corresponding pairs of actual capturing positions,
wherein the portion-by-portion capturing is performed such that the secondary constraint limits, in dependence on the error statistics, the difference of capturing position variables for pairs of subimages which immediately follow one another along the capturing path.
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 is:
1. A method comprising administering a therapeutically effective amount of an agent to a mammal which has an allergic or inflammatory disease, wherein said agent inhibits an activity or expression of a component of an arginine metabolic pathway in a tissue affected by the disease, and said component is not a nitric oxide synthase (NOS).
2. The method of claim 1, wherein the disease is a respiratory disease.
3. The method of claim 2, wherein the respiratory disease is asthma, chronic airway remodeling, or chronic obstructive pulmonary disease (COPD).
4. The method of claim 3, wherein said agent is capable of binding to the component or a polynucleotide encoding the component.
5. The method of claim 4, wherein said component is an arginase.
6. The method of claim 4, wherein said component is a cationic amino acid transporter.
7. The method of claim 4, wherein said component is downstream of an arginase in the pathway.
8. The method of claim 2, wherein said agent inhibits the expression of the component by RNA interference or an antisense mechanism.
9. The method of claim 8, wherein said agent encodes or comprises an siRNA capable of inhibiting the expression of ARG1 in said tissue by RNA interference.
10. The method of claim 8, wherein said agent encodes or comprises an siRNA capable of inhibiting the expression of CAT2 in said tissue by RNA interference.
11. The method of claim 2, wherein said agent is -difluoromethylornithine.
12. The method of claim 2, wherein said agent is lysine or a cationic polypeptide.
13. The method of claim 1, wherein the mammal is a human.
14. The method of claim 13, wherein said human has asthma or COPD, and said component is an arginase or a cationic amino acid transporter, and wherein said agent is capable of binding to said component or a polynucleotide encoding said component.
15. A method for identifying an agent for treating an allergic or inflammatory disease, comprising:
contacting a molecule with a tissue affected by asthma or another allergic or inflammatory disease, wherein said molecule is capable of binding to a non-NOS component of an arginine metabolic pathway or to a polynucleotide encoding said component; and
determining if said molecule is capable of ameliorating or eliminating a syndrome or phenotype associated with said asthma or disease.
16. The method of claim 15, wherein said molecule is selected or produced based on a structure-based rational drug design or based on screening a compound library.
17. The method of claim 15, wherein said component is an arginase or a cationic amino acid transporter.
18. A method, comprising:
detecting an expression profile of at least one gene in a biological sample of a mammal; and
comparing said expression profile to a reference expression profile of said at least one gene to determine if the mammal has or is at risk for an allergic or inflammatory disease,
wherein said one gene encodes a non-NOS component of an arginine metabolic pathway.
19. The method of claim 18, wherein the disease is asthma.
20. A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and an agent capable of inhibiting an activity or expression of a non-NOS component of an arginine metabolic pathway.