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S Webb

Publications and source records attributed to S Webb.

At least 73 records · Page 4Linked to original sources
PubMed1999

Molecular cloning of a pancreatic islet-specific glucose-6-phosphatase catalytic subunit-related protein.

A pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP) was cloned using a subtractive cDNA expression cloning procedure from mouse insulinoma tissue. Two alternatively spliced variants that differed by the presence or absence of a 118-bp exon (exon IV) were detected in normal balb/c mice, diabetic ob/ob mice, and insulinoma tissue. The longer, 1901-bp full-length cDNA encoded a 355-amino acid protein (molecular weight 40,684) structurally related (50% overall identity) to the liver glucose-6-phosphatase and exhibited similar predicted transmembrane topology, conservation of catalytically important residues, and the presence of an endoplasmic reticulum retention signal. The shorter transcript encoded two possible open reading frames (ORFs), neither of which possessed His174, a residue thought to be the phosphoryl acceptor (Pan CJ, Lei KJ, Annabi B, Hemrika W, Chou JY: Transmembrane topology of glucose-6-phosphatase. J Biol Chem 273:6144-6148, 1998). Northern blot and reverse transcription-polymerase chain reaction analysis showed that the mRNA was highly expressed in pancreatic islets and expressed more in beta-cell lines than in an alpha-cell line. It was notably absent in tissues and cell lines of non-islet neuroendocrine origin, and no other major tissue source of the mRNA was found. During development, it was expressed in parallel with insulin mRNA. The mRNA was efficiently translated and glycosylated in an in vitro translation/membrane translocation system and readily transcribed into COS 1, HIT, and CHO cells using cytomegalovirus or Rous sarcoma virus promoters. Whereas the liver glucose-6-phosphatase showed activity in these transfection systems, the IGRP failed to show glucose phosphotransferase or phosphatase activity with p-nitrophenol phosphate, inorganic pyrophosphate, or a range of sugar phosphates hydrolyzed by the liver enzyme. While the metabolic function of the enzyme is not resolved, its remarkable tissue-specific expression warrants further investigation, as does its transcriptional regulation in conditions where glucose responsiveness of the pancreatic islet is altered.

Alternative Splicing↗
PubMed1999

Apoptosis and carcinogenesis.

Apoptosis has long been known to be effected through a common sequence of structural changes, despite the wide variety of initiating stimuli. These common structural events appear to depend upon activation of a set of enzymes (caspases) which direct a strongly conserved, terminal effector pathway. The regulation of this pathway, and in particular its coupling to DNA damage, appears to be critical in maintaining at low levels the number of mutated cells within tissues. The frequency with which tumours (experimental and human) bear deficiency in p53 or MSH-2 repair function may indicate the importance of these proteins in coupling DNA damage to apoptosis.

Animals↗
PubMed1998

Comparison of 2D and 3D algorithms for adding a margin to the gross tumor volume in the conformal radiotherapy planning of prostate cancer.

PURPOSE: To evaluate the adequacy of tumor volume coverage using a three-dimensional (3D) margin-growing algorithm compared to a two-dimensional (2D) margin-growing algorithm in the conformal radiotherapy planning of prostate cancer. METHODS AND MATERIALS: Two gross tumor volumes (GTV) were segmented in each of 10 patients with localized prostate cancer; prostate gland only (PO) and prostate with seminal vesicles (PSV). A predetermined margin of 10 mm was applied to these two groups (PO and PSV) using both 2D and 3D margin-growing algorithms. The 2D algorithm added a transaxial margin to each GTV slice, whereas the 3D algorithm added a volumetric margin all around the GTV. The true planning target volume (PTV) was defined as the region delineated by the 3D algorithm. The adequacy of geometric coverage of the GTV by the two algorithms was examined in a series of transaxial planes throughout the target volume. RESULTS: The 2D margin-growing algorithm underestimated the PTV by 17% (range 12-20) in the PO group and by 20% (range 13-28) for the PSV group when compared to the 3D-margin algorithm. For the PO group, the mean transaxial difference between the 2D and 3D algorithm was 3.8 mm inferiorly (range 0-20), 1.8 mm centrally (range 0-9), and 4.4 mm superiorly (range 0-22). Considering all of these regions, the mean discrepancy anteriorly was 5.1 mm (range 0-22), posteriorly 2.2 (range 0-20), right border 2.8 mm (range 0-14), and left border 3.1 mm (range 0-12). For the PSV group, the mean discrepancy in the inferior region was 3.8 mm (range 0-20), central region of the prostate was 1.8 mm ( range 0-9), the junction region of the prostate and the seminal vesicles was 5.5 mm (range 0-30), and the superior region of the seminal vesicles was 4.2 mm (range 0-55). When the different borders were considered in the PSV group, the mean discrepancies for the anterior, posterior, right, and left borders were 6.4 mm (range 0-55), 2.5 mm (range 0-20), 2.6 mm (range 0-14), and 3.9 mm (range 0-45), respectively. Underestimation of the required margin with the 2D algorithm occurred when the transaxial definition of the GTV shifted in position significantly between successive adjacent slices, resulting in transaxial discrepancies of up to 22 mm and 55 mm, respectively, for the PO and PSV groups. In the superior regions, the 2D algorithm was inadequate, often providing a margin of less than 3 mm compared to the 10 mm margin delineated by the 3D algorithm. CONCLUSION: This study illustrates that target margins added by a laminar method in the transaxial plane are inadequate for covering a 3D tumor volume so that a margin-growing algorithm which fully takes into account the 3D shape of the GTV should be used. If a 2D-margin method is utilized, an appreciation of spatial margins in 3D is required.

Aged↗
PubMed1998

Targeted disruption of p70(s6k) defines its role in protein synthesis and rapamycin sensitivity.

Here, we disrupted the p70 S6 kinase (p70(s6k)) gene in murine embryonic stem cells to determine the role of this kinase in cell growth, protein synthesis, and rapamycin sensitivity. p70(s6k-/-) cells proliferated at a slower rate than parental cells, suggesting that p70(s6k) has a positive influence on cell proliferation but is not essential. In addition, rapamycin inhibited proliferation of p70(s6k-/-) cells, indicating that other events inhibited by the drug, independent of p70(s6k), also are important for both cell proliferation and the action of rapamycin. In p70(s6k-/-) cells, which exhibited no ribosomal S6 phosphorylation, translation of mRNA encoding ribosomal proteins was not increased by serum nor specifically inhibited by rapamycin. In contrast, rapamycin inhibited phosphorylation of initiation factor 4E-binding protein 1 (4E-BP1), general mRNA translation, and overall protein synthesis in p70(s6k-/-) cells, indicating that these events proceed independently of p70(s6k) activity. This study localizes the function of p70(s6k) to ribosomal biogenesis by regulating ribosomal protein synthesis at the level of mRNA translation.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Formation of the atrioventricular septal structures in the normal mouse.

It is sometimes thought that formation of the atrioventricular septum is equated with fusion of the endocardial cushions and that failure of fusion can explain all deficiencies of atrioventricular septation. Clearly, this is simplistic, but the exact contribution of different primordia to atrioventricular septation is not well understood. To clarify this, we studied normal mouse embryos (days 10 to 15 of gestation), which were serially sectioned and examined by light microscopy. Another group of embryos was examined by scanning electron microscopy after microdissection. Our results show that development of the atrioventricular septal area is highly complex. Proper formation requires the following: remodeling of the inner heart curvature, rotation of the horns of the systemic venous sinus around the pulmonary portal, expansion of the right atrioventricular junction, formation of the muscular atrial and ventricular septa, bridging by the dextrodorsal outflow ridge and the superior endocardial cushion, fusion with the inferior margins of the venous valves, and formation of the mouth of the coronary sinus from the cranial muscular wall of the left sinus horn. Multiple primordia contribute to a central mesenchymal mass (the "septum intermedium"), including the mesenchyme on the leading edge of the primary atrial septum, the atrioventricular endocardial cushions, and the cap of mesenchyme on the spina vestibuli. Fusion of these components closes the ostium primum, completing atrial and atrioventricular septation. Additionally, the spina vestibuli has a mesodermal core, which contributes to the muscularization of the lower margin of the oval fossa. This contrasts with the formation of the upper rim, which occurs as a result of an infolding of the atrial wall itself.

Animals↗
PubMed1998

Development of the murine pulmonary vein and its relationship to the embryonic venous sinus.

BACKGROUND: Arguments concerning the development of the pulmonary vein, and its relationship to the embryonic venous sinus (sinus venosus) have continued for well over a century. Recently, attention has again been focused on the origin of the pulmonary vein. It has been suggested that, whereas the pulmonary vein originates from the left atrium in humans, in all other vertebrates it originates from the venous sinus, with subsequent transfer to the left atrium. The nature of this transfer has not, however, been elucidated, although there is speculation that the pulmonary vein is "pinched off" from the left side of the embryonic venous sinus. METHODS: We studied closely staged hearts of normal mouse embryos from a C57BL/6 x CBAcross days 10 and 11 of gestation (plug day = day 1). Two series of embryos were collected and fixed in 2% glutaraldehyde, 1% formaldehyde, buffered with 0.05 M sodium cacodylate pH 7.4 (adjusted to 330 mOsm with NaCl). One series was wax embedded, serially sectioned, and stained with Masson's trichrome. The second series was subject to microdissection and scanning electron microscopy. RESULTS: The atrial component of the heart tube is attached to the body of the embryo by reflections of the atrial myocardial wall. The attachment can be considered, from the outset, as the heart stalk, with the myocardial-mesodermal connections forming a horseshoe of tissue that projects ventrally into the lumen of the atrium, surrounding a single evagination in the midline of the embryo. This heart stalk is cranial to the connections of the tributaries of the embryonic venous sinus and ventral to the foregut. When traced through its developmental stages, the evagination in the centre of the stalk, which we describe as the pulmonary pit, is seen to become the portal of entry for the developing pulmonary vein. CONCLUSIONS: The heart stalk, representing the area used by the pulmonary vein to gain access to the heart, and analogous to the dorsal mesocardium, is, from the outset, discrete from the area occupied by the orifices of the horns of the embryonic venous sinus. The pulmonary vein does not, in the mouse, develop from the tissues that form the walls of the tributaries of the systemic venous sinus. Comparisons with other studies suggest that early events in the development of the pulmonary vein are likely to be the same in all mammals, including humans.

Animals↗
PubMed1998

The mouse with trisomy 16 as a model of human hearts with common atrioventricular junction.

OBJECTIVE: To establish if the mouse with trisomy 16 is a suitable animal model with which to elucidate the development of a common atrioventricular junction. METHODS: The junctional morphologies in the normal human heart and those with a common atrioventricular junction are compared and contrasted. These are then related to observations made in normal mice and those with trisomy 16. So as better to understand development, a full description is given first of the normal atrioventricular junctions. Developmental implications are discussed because failure of fusion of the endocardial cushions cannot account for all the anomalies found in RXR alpha knockout, and in iv/iv mice. RESULTS: Mice with trisomy 16 showed evidence of deficiencies of atrioventricular septation and possessed a common atrioventricular junction, but the valvar orifices were not balanced between the ventricles as is the case in humans. Whilst some mice showed affinities with human tricuspid atresia, other cardiac malformations in the mice had no counterparts in human cardiac pathology. In humans both "partial" and "complete" forms of "atrioventricular canal malformations" share a basically common muscular junctional morphology, the differences being due exclusively to the way the bridging leaflets are fused to each other and/or the septum. CONCLUSIONS: It is simplistic to use the mouse with trisomy 16 as a model for cardiac abnormalities seen in humans. A spectrum more comparable to humans is found in RXR knockout mice. Study of the iv/iv mouse may help elucidate the genetic steps involved in normal and abnormal atrioventricular septation.

Animals↗
PubMed1998

A cone-beam megavoltage CT scanner for treatment verification in conformal radiotherapy.

PURPOSE: A prototype scanner for large-volume megavoltage computed tomography (MVCT) in a clinical set-up is described. The ultimate aim is to improve treatment accuracy in conformal radiotherapy through patient set-up error reduction and transit dosimetry. MATERIALS AND METHODS: The scanner consists of a custom-built 2D CsI(Tl) crystal array viewed by a lens and a CCD camera. Image acquisition is synchronized with radiation pulses. The 2D projections resulting from a single continuous 360 degrees gantry rotation are reconstructed using a cone-beam tomography algorithm. Prior to reconstruction, the raw projections are calibrated and corrected for centre of rotation movement and accelerator output fluctuation. The performance of the system has been evaluated by reconstructing projections of open fields, test objects and a humanoid phantom. RESULTS: Hundreds of 2D projections can be acquired with a clinically-acceptable data collection time (about 2 min) and dose (approximately 40 cGy, with a possible four-fold reduction). A maximum density resolution of about 2% is achieved offering some soft tissue discrimination without using image enhancement tools. A spatial resolution of 2.5 mm is obtained. The reconstructed image intensity is linear with electron density over the range of interest. Coronal or sagittal slices through the 3D reconstruction of the humanoid phantom show a better delineation of structures than the corresponding portal images taken at the same orientation. CONCLUSIONS: A similar image quality to our current single-slice MVCT scanner is achieved with the advantage of providing tens of tomographic slices for a single gantry rotation. This work demonstrates the feasibility of clinical cone-beam MVCT and indicates how this prototype can be improved.

Image Processing, Computer-Assisted↗
PubMed1998

Defective lateralisation in children with congenitally malformed hearts.

Defects in lateralization can be studied from the stance of populations, the individual, or the systems of organs within each individual. Unfortunately, and confusingly, the same terms are being applied to each of these situations, but inevitably with different meanings. Thus, there is presently no consensus on how we should use terms such as "heterotaxy" and "situs ambiguus". By far the least ambiguous use of these words is encountered when they are applied to the organs. In fact, each system of organs can accurately and simply be described in terms of its left-right morphology. All those organs which are paired then can be described, when interpreted on the basis of their intrinsic morphology, as being usually arranged, mirror-imaged, or as showing left or right isomerism. Within the heart, these changes are seen only in the atrial segment. The criterion for distinction of rightness or leftness within the atrial segment is the extent of the pectinate muscles relative to the atrioventricular junction. Application of this criterion permits unequivocal recognition of symmetry as opposed to lateralization. The same holds good for the other organs. Within any individual organ, therefore, the situation is neither ambiguous nor heterotaxic. Instead, it is lateralised or symmetrical. Within the individual, in contrast, there may well be discrepancies in the expected disposition of the systems of organs which produces potential ambiguity. To dispel this ambiguity, it is necessary to provide a full catalogue. For example, persons with otherwise normally arranged organs may have left bronchial isomerism. Other persons may have discordance between the thoracic organs, which are usually arranged, and the abdominal organs, which are mirror-imaged, but no evidence of isomerism. Within the population, however, we are unaware of any genetically or environmentally induced syndrome in which all individuals show evidence of mirror-imagery, or of isomerism, or of specific discordance between the systems. In fact, all known syndromes encompass all types of defective lateralization. When attempting to identify the genetic mechanisms for production of the syndromes, therefore, it could be positively misleading to attempt to separate isomerism from other perceived forms of"heterotaxy". Our preference is to consider any deviation from the usual arrangement as heterotaxy, and to specify the specific arrangement of the organs within each malformed individual.

Child↗
PubMed1998

Improving calibration accuracy in gel dosimetry.

A new method of calibrating gel dosimeters (applicable to both Fricke and polyacrylamide gels) is presented which has intrinsically higher accuracy than current methods, and requires less gel. Two test-tubes of gel (inner diameter 2.5 cm, length 20 cm) are irradiated separately with a 10 x 10 cm2 field end-on in a water bath, such that the characteristic depth-dose curve is recorded in the gel. The calibration is then determined by fitting the depth-dose measured in water, against the measured change in relaxivity with depth in the gel. Increased accuracy is achieved in this simple depth-dose geometry by averaging the relaxivity at each depth. A large number of calibration data points, each with relatively high accuracy, are obtained. Calibration data over the full range of dose (1.6-10 Gy) is obtained by irradiating one test-tube to 10 Gy at dose maximum (Dmax), and the other to 4.5 Gy at Dmax. The new calibration method is compared with a 'standard method' where five identical test-tubes of gel were irradiated to different known doses between 2 and 10 Gy. The percentage uncertainties in the slope and intercept of the calibration fit are found to be lower with the new method by a factor of about 4 and 10 respectively, when compared with the standard method and with published values. The gel was found to respond linearly within the error bars up to doses of 7 Gy, with a slope of 0.233 +/- 0.001 s(-1) Gy(-1) and an intercept of 1.106 +/- 0.005 Gy. For higher doses, nonlinear behaviour was observed.

Acrylamides↗
PubMed1998

Inverse planning with constraints to generate smoothed intensity-modulated beams.

Highly conformal dose distributions can be generated by intensity-modulated radiotherapy. Intensity-modulated beams (IMBs) are generally determined by inverse-planning techniques designed to maximize conformality. Usually such techniques apply no constraints on the form of the IMBs which may then develop fine-scale modulation. In this paper we present a technique for generating smoother IMBs, which yields a dose distribution almost identical to that without the constraint on the form of the IMBs. The method applies various filters successively at intervals throughout the iterative inverse planning. It is shown that the IMBs so determined using a simple median window filter have desirable properties in terms of increasing the efficiency of delivery by the dynamic multileaf collimator method and may be 'more like conventional beams' than unconstrained, highly modulated IMBs.

Humans↗
PubMed1998

Configuration options for intensity-modulated radiation therapy using multiple static fields shaped by a multileaf collimator.

One-dimensional (1D) intensity-modulated beams (IMBs) can be generated by multiple static fields (MSFs) created by a multileaf collimator (MLC) with the radiation switched off between field re-settings (Bortfeld-Boyer method). Each component irradiation is of equal fluence. This paper presents and analyses the formulae for the number of physically allowed combinations of leaf settings which generate any given IMB. The formulae are general to an IMB with any number of local minima and extend from the well-known N! formula for a single-peaked IMB with N left-leaf (L-leaf) and N right-leaf (R-leaf) positions. A 'combination' is a set of N L-leaf and R-leaf pairings. A 'physically allowed combination' is one in which no L-leaf is paired with an R-leaf to its left. The physically allowed combinations are grouped by specific properties into classes in which the well-known techniques of 'leaf-sweep' and 'close-in' are just two members. Consideration of these properties leads to a new suggestion of the 'forced-baseline' configuration in which the first intensity increment is delivered for the full field width and there remain choices concerning the delivery of the rest of the IMB within which two different possibilities are 'one-out-of-sync leaf-sweep' and 'minimum leaf travel'. The extension to 2D is briefly introduced.

Models, Theoretical↗
PubMed1998

An investigation into the dosimetry of a nine-field tomotherapy irradiation using BANG-gel dosimetry.

BANG-gel dosimetry offers the potential for measuring the dose delivered by a radiotherapy treatment technique, in three dimensions, with high spatial resolution and good accuracy. The ability to measure comprehensively a 3D dose distribution is a major advantage of the gel dosimeter over conventional planar and point-based dosimeter devices, particularly when applied to the verification of complex dose distributions characteristic of intensity-modulated radiotherapy (IMRT). In this paper an in-house manufactured BANG-gel dosimeter was applied to study the dose distributions of two irradiation experiments for which the distributions were known: (i) a dosimetrically simple parallel-opposed irradiation, and (ii) a more complex nine-field 'static tomotherapy' intensity-modulated irradiation delivered with the Nomos MIMiC. The uniform distribution in (i) allowed a study of the magnetic resonance (MR) imaging parameters to achieve an optimal trade-off between noise and image resolution (optimum image resolution for the Siemens 1.5T Vision system was determined to be approximately 0.8 mm2 with a slice thickness of 2 mm). The spatial uniformity of gel sensitivity to radiation was found to depend strongly on the presence of oxygen, which must be eliminated for the gel dosimeter to be of use. The gel dosimeter was found to agree well with predicted dose distributions and accurately measured the steep penumbral fall-off of dose, even after many days, proving its potential for the verification of IMRT distributions. In the nine-field IMRT delivery (ii) the predicted dose was computed by both an in-house 'component-delivery' dose algorithm and the Peacock planning-system dose algorithm. Good agreement was found between the two algorithms despite the latter's omission of the change in penumbral characteristics with aperture-size during delivery, lack of inhomogeneity correction and approximate modelling of leaf leakage. These effects were found to be small for the problem studied. The predicted distribution agreed well with the gel-measured distribution at medium and high doses (50-90% isodose lines) although differences of up to 10% were observed at lower doses (30% isodose line). The gel dosimeter was found to have the potential to verify IMRT distributions but required considerable care to achieve accurate results. Attention was required to achieve uniformity of gel sensitivity (to prevent oxygen contamination), and in the calibration process.

Acrylamide↗
PubMed1998

Configuration options for intensity-modulated radiation therapy using multiple static fields shaped by a multileaf collimator. II: constraints and limitations on 2D modulation.

This paper addresses the technique of using multiple static multileaf-collimator-shaped field components to create a two-dimensional intensity-modulated beam (2D IMB). It addresses the physical constraints on the problem of determining the optimum field-component leaf configurations under the circumstances that (i) the static field components are shaped by leaves alone and (ii) the 2D intensity distribution is delivered by exactly N field components when there are N rising-intensity equal-fluence increments in the 1D channel containing the maximum fluence in the 2D IMB. This corresponds to the least inefficient delivery. In general it is noted that an optimum solution (set of field-component leaf configurations) with zero tongue-and-groove underdose may not exist (depending on the distribution) and an exhaustive search for the set of leaf configurations with the minimum tongue-and-groove underdose is impossible for realistically sized problems. Against this background iterative methods to examine a limited search space are shown to yield an optimum solution with zero tongue-and-groove underdose for certain intensity distributions. These searches are not robust and can be defeated. The problem of finding an optimum solution may be generally insoluble for some 2D IMBs under the conditions (i) and (ii). If, however, a larger number of field components is permitted and/or the accelerator jaws may also be used, in addition to the multileaves, then an optimum solution with zero tongue-and-groove underdose can always be found with lower efficiency.

Biophysical Phenomena↗
PubMed1998

A case study comparing the relative benefit of optimizing beam weights, wedge angles, beam orientations and tomotherapy in stereotactic radiotherapy of the brain.

A treatment-planning case study has been performed on a patient with a medium-sized, convex brain tumour. The study involved the application of advanced treatment-plan optimization techniques to improve on the dose distribution of the 'standard plan' used to treat the patient. The standard plan was created according to conventional protocol at the Royal Marsden NHS Trust, and consisted of a three-field (one open and two wedged) non-coplanar arrangement, with field shaping to the beam's-eye view of the planning target volume (PTV). Three optimized treatment plans were created corresponding to (i) the optimization of the beam weights and wedge angles of the standard plan, (ii) the optimization of the beam orientations, beam weights and wedge angles of the standard plan, and (iii) a full fluence tomotherapy optimization of 1 cm wide (at isocentre), 270 degree arcs. (i) and (ii) were created on the VOXELPLAN research 3D treatment-planning system, using in-house developed optimization algorithms, and (iii) was created on the PEACOCK tomotherapy planning system. The downhill-simplex optimization algorithm is used, in conjunction with 'threshold-dose' cost-function terms enabling the algorithm to optimize specific regions of the dose-volume histogram (DVH) curve. The 'beam-cost plot' tool is presented as a visual aid to the selection of beneficial beam directions. The methods and pitfalls in the transfer of plans and patient data between the two planning systems are discussed. Each optimization approach was evaluated, relative to the standard plan, on the basis of DVH and dose statistics in the PTV and organs at risk (OARs). All three optimization approaches were able to improve on the dose distribution of the standard plan. The magnitude of the improvement was greater for the optimized beam-orientation and tomotherapy plans (up to 15% and 30% for the maximum and mean OAR doses). A smaller improvement was observed in the beam-weight and wedge-angle optimized plan (up to 5% and 10% in the maximum and mean OAR doses). In the tomotherapy plan, difficulty was encountered achieving an acceptable homogeneity of dose in the PTV. This was improved by treating the gross tumour volume (GTV) and (PTV - GTV) regions as separate targets in the inverse planning, with the latter region prescribed a slightly higher dose to reduce edge under-dosing. In conclusion, for the medium-sized convex tumour studied, the tomotherapy dose distribution showed a significant improvement on the standard plan, but no significant improvement over a conventional three-field plan where the beam orientations, beam weights and wedge angles had been optimized.

Adenoma↗
PubMed1998

Generation of discrete beam-intensity modulation by dynamic multileaf collimation under minimum leaf separation constraints.

An algorithm to generate discrete beam-intensity modulation by dynamic multileaf collimation is presented which incorporates constraints on minimum allowed leaf separations. MLC positioning information is derived simultaneously for all leaf pairs and back-up diaphragms as they progress across the field. A feedback mechanism allows corrections to be applied to eliminate potential violations of minimum separation conditions and any underexposure in the interleaf tongue-and-groove region as they are encountered. The resulting motion correctly delivers the intended modulation and is physically realizable. Implementation of the algorithm is described. Results of the algorithm can also alternatively be interpreted as defining a series of static fields to deliver the same modulation.

Algorithms↗