1. Preferably recombinant DNA, from Corynebacterium, which is replicatable in coryneform microorganisms and which contains at least the nucleotide sequence which encodes for the sod gene represented in SEQ-ID-No. 1.
2. Replicable DNA in accordance with claim 1 comprising
(i) the nucleotide sequence, shown in SEQ-ID-No.1, or
(ii) at least one sequence which corresponds to the sequence (i) within the region of degeneration of the genetic code, or
(iii) at least one sequence which hybridizes with the sequence which is complementary to sequence (i) or (ii) and optionally
(iv) functionally neutral sense mutations in (i).
3. An amino acid sequence for the protein derived from the nucleotide sequences in accordance with claims 1 or 2, represented in SEQ-ID-No. 2.
4. Coryneform microorganisms, in particular the genus Corynebacterium, transformed by the introduction of one or more of the replicatable DNA’s in accordance with one of claims 1 or 2.
5. Shuttle vector pMM23, characterised by the restriction chart given in FIG. 1 and deposited in Escherichia coli under the name DSM 12860.
6. A process for increasing the superoxide dismutase activity in coryneform bacteria, wherein the sod gene, or nucleotide sequences encoding therefor, is amplified, in particular overexpressed.
7. A process for preparing metabolic products, in particular L-lysine, by fermentation of coryneform bacteria, wherein bacteria are used in which the sod gene or nucleotide sequences encoding therefor is amplified, in particular overexpressed.
8. A process according to claim 7, wherein bacteria are used in which other genes in the biosynthetic pathway of the desired metabolic product are amplified.
9. A process according to claim 7, wherein bacteria are used in which metabolic pathways which reduce production of the desired metabolic product are at least partly switched off.
10. A process according to claims 7 to 9, wherein a strain which has been transformed with a plasmid vector is used and the plasmid vector carries the nucleotide sequence encoding for the sod gene.
11. A process according to claim 9, wherein bacteria transformed with the plasmid vector pMM23, deposited in Escherichia coli under the number DSM 12860, is used.
12. A process according to one or more of the preceding Claims, wherein coryneform bacteria are used which produce nucleotides, vitamins and amino acids.
13. A process according to one or more of the preceding Claims, wherein the coryneform bacteria used produce L-lysine.
14. A process according to claim 8 to produce nucleotides, wherein the purF gene encoding for glutamine-PRPP-amidotransferase is simultaneously overexpressed.
15. A process according to claim 8 to prepare nucleotides, wherein the carAB gene encoding for carbamoyl synthetase is simultaneously overexpressed.
16. A process according to claim 8 for preparing D-pantothenic acid, wherein the panD gene encoding for aspartate decarboxylase is simultaneously overexpressed.
17. A process according to claim 8 for preparing L-lysine, wherein the dapA gene encoding for dihydrodipicolinate synthase is simultaneously overexpressed.
18. A process according to claim 8 for preparing L-lysine, wherein a DNA fragment promoting S-(2-aminoethyl)cysteine resistance is simultaneously amplified.
19. A process for the fermentative preparation of the desired metabolic products in accordance with one or more of the preceding Claims, wherein the following steps are performed:
a) fermentation of the coryneform bacteria which produce the desired metabolic product, in which at least the sod gene is amplified,
b) enrichment of the desired metabolic product in a medium or in the cells of the bacteria and
c) isolation of the desired product.
20. A process for the fermentative preparation of L-amino acids according to claim 19, wherein the following steps are performed:
a) fermentation of the coryneform bacteria which produce the desired metabolic product, in which at least the sod gene is amplified,
b) enrichment of the desired metabolic product in a medium or in the cells of the bacteria and
c) isolation of the desired product.
21. A process for the fermentative preparation of D-pantothenic acid according to claim 19, wherein the following steps are performed:
a) fermentation of the coryneform bacteria which produce D-pantothenic acid, in which at least the sod gene is amplified,
b) enrichment of D-pantothenic acid in a medium or in the cells of the bacteria and
c) isolation of this acid.
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 for ultrasonically imaging with an ultrasonic contrast agent comprising:
transmitting pulses to an image region of a subject;
receiving echoes from a contrast agent in the image region in response to the transmitted pulses;
detecting the location of a contrast agent in the image region at a given point in time; and
producing an image showing the locations of the contrast agent at different points in time.
2. The method of claim 1, further comprising:
forming an image in response to the received echoes; and
wherein detecting comprises temporally high pass filtering temporally different images to detect the location of a contrast agent at a given point in time.
3. The method of claim 2, wherein temporally high pass filtering comprises performing frame-to-frame subtraction on a spatial basis of temporally different image frames.
4. The method of claim 3, wherein temporally high pass filtering comprises performing frame-to-frame subtraction on a spatial basis of successive image frames.
5. The method of claim 1, wherein producing an image comprises producing an image in which the display of the location of a contrast agent at a given point in time persists over a plurality of image intervals.
6. The method of claim 5, wherein producing an image comprises displaying a maximum intensity projection of the locations of a contrast agent.
7. The method of claim 5, wherein producing an image comprises displaying the location of a contrast agent at a given point in time with a slow decay persistence over a plurality of image intervals.
8. The method of claim 5, wherein producing an image comprises processing image pixel data on a spatial basis in accordance with:
OutputPixel(x,y,k)maxabsInputPixel(x,y,k),P*OutputPixel(x,y,k1),
where x and y are pixel coordinates, P is a time constant ranging from 0 to 1, and k is a time marker.
9. A method for ultrasonically imaging with an ultrasonic contrast agent comprising:
producing a first data set of the location of a moving contrast agent at a first time;
producing a second data set of the location of the moving contrast agent at a second time; and
producing an image for display which depicts the locations of the moving contrast agent at the first and second times.
10. The method of claim 9, further comprising temporally high pass filtering the first and second data sets.
11. The method of claim 10, wherein temporally high pass filtering the first and second data sets comprises performing subtraction of the first and second data sets on a spatial basis.
12. The method of claim 9, wherein producing an image for display comprises persistence processing contrast agent location information.
13. The method of claim 9, wherein the contrast agent is a harmonic contrast agent and wherein producing an image for display comprises producing an image showing the path of movement of a contrast agent over time.
14. A method for ultrasonically imaging with an ultrasonic contrast agent comprising:
producing a first data set of the location of a moving harmonic contrast agent at a first time;
producing a second data set of the location of the moving harmonic contrast agent at a second time; and
producing an image for display which depicts a track of the locations of the moving harmonic contrast agent at different points in time.
15. An ultrasonic imaging system for harmonic contrast imaging comprising:
an array transducer which interrogates an image field containing a moving contrast agent;
a receiver coupled to the array transducer which produces coherent echo signals from the moving contrast agent;
an image processor coupled to the receiver which produces images showing the locations of the moving contrast agent at different points in time;
an inter-frame high pass filter coupled to the image processor;
a persistence processor coupled to the inter-frame high pass filter which produces images depicting the locations of the moving contrast agent at earlier points in time; and
an image display.
16. The ultrasonic imaging system of claim 15, wherein the inter-frame high pass filter comprises a frame-to-frame subtractor.
17. The ultrasonic imaging system of claim 15, wherein the persistence processor utilizes a persistence time constant to cause the location of the moving contrast agent at a given point in time to persist over a plurality of image intervals.
18. The ultrasonic imaging system of claim 17, wherein the persistence time constant causes the location of the moving contrast agent at a given point in time to persist indefinitely.
19. The ultrasonic imaging system of claim 17, wherein the persistence time constant causes the location of the moving contrast agent at a given point in time to persist with a slow decay.
20. The ultrasonic imaging system of claim 15, wherein the image display acts to display an image depicting the tracks of microbubbles through small blood vessels over time.
21. The ultrasonic imaging system of claim 15, further comprising an image registration processor coupled to the image processor.