Contribution of disparity to the perception of 3D shape as revealed by bistability of stereoscopic Necker cubes.

The Necker cube is a famous demonstration of ambiguity in visual perception of 3D shape. Its bistability is attributed to indecisiveness because monocular cues do not allow the observer to infer one particular 3D shape from the 2D image. A remarkable but not appreciated observation is that Necker cubes are bistable during binocular viewing. One would expect disparity information to veto bistability. To investigate the effect of zero and non-zero disparity on perceptual bistability in detail, perceptual dominance durations were measured for luminance- and disparity-defined Necker cubes. Luminance-defined Necker cubes were bistable for all tested disparities between the front and back faces of the cubes. Absence of an effect of disparity on dominance durations suggested the suppression of disparity information. Judgments of depth between the front and back sides of the Necker cubes, however, showed that disparity affected perceived depth. Disparity-defined Necker cubes were also bistable but dominance durations showed different distributions. I propose a framework for 3D shape perception in which 3D shape is inferred from pictorial cues acting on luminance- and disparity-defined 2D shapes.

Depth cue combination in spontaneous eye movements.

Where we look when we scan visual scenes is an old question that continues to inspire both fundamental and applied research. Recently, it has been reported that depth is an important variable in driving eye movements: the directions of spontaneous saccades tend to follow depth gradients, or, equivalently, surface tilts (L. Jansen, S. Onat, & P. König, 2009; M. Wexler & N. Ouarti, 2008). This has been found to hold for both simple and complex scenes and for a variety of depth cues. However, it is not known whether saccades are aligned with individual depth cues, or with a combination of depth cues. If saccades do follow a combination of depth cues, then it is interesting to ask whether this combination follows the same rules as the well-studied case of depth cue combination in conscious perception. We showed subjects surfaces inclined in depth, in which perspective and binocular disparity cues specified different plane orientations, with different degrees of both small and large conflict between the two sets of cues. We recorded subjects' spontaneous saccades while they scanned the scene, as well as their reports of perceived plane orientation. We found that distributions of spontaneous saccade directions followed the same pattern of depth cue combination as perceived surface orientation: a weighted linear combination of cues for small conflicts, and cue dominance for large conflicts. The weights assigned to the cues varied considerably from one subject to the next but were strongly correlated for saccades and perception; moreover, for both perception and saccades, cue weights could be modified by manipulating cue reliability in a way compatible with Bayesian theories of optimal cue combination. We also measured vergence, which allowed us to calculate the orientation of the plane fitted to points scanned in depth. Contrary to perception and saccades, vergence was dominated by a single cue, binocular disparity.

Depth cues, rather than perceived depth, govern vergence.

We studied the influence of perceived surface orientation on vergence accompanying a saccade while viewing an ambiguous stimulus. We used the slant rivalry stimulus, in which perspective foreshortening and disparity specified opposite surface orientations. This rivalrous configuration induces alternations of perceived surface orientation, while the slant cues remain constant. Subjects were able to voluntarily control their perceptual state while viewing the ambiguous stimulus. They were asked to make a saccade across the perceived slanted surface. Our data show that vergence responses closely approximated the vergence response predicted by the disparity cue, irrespective of voluntarily controlled perceived orientation. However, comparing the data obtained while viewing the ambiguous stimulus with data from an unambiguous stimulus condition (when disparity and perspective specified similar surface orientations) revealed an effect of perspective cues on vergence. Collectively our results show that depth cues rather than perceived depth govern vergence.

Coarse-to-fine eye movement strategy in visual search.

Oculomotor behavior contributes importantly to visual search. Saccadic eye movements can direct the fovea to potentially interesting parts of the visual field. Ensuing stable fixations enables the visual system to analyze those parts. The visual system may use fixation duration and saccadic amplitude as optimizers for visual search performance. Here we investigate whether the time courses of fixation duration and saccade amplitude depend on the subject's knowledge of the search stimulus, in particular target conspicuity. We analyzed 65,000 saccades and fixations in a search experiment for (possibly camouflaged) military vehicles of unknown type and size. Mean saccade amplitude decreased and mean fixation duration increased gradually as a function of the ordinal saccade and fixation number. In addition we analyzed 162,000 saccades and fixations recorded during a search experiment in which the location of the target was the only unknown. Whether target conspicuity was constant or varied appeared to have minor influence on the time courses of fixation duration and saccade amplitude. We hypothesize an intrinsic coarse-to-fine strategy for visual search that is even used when such a strategy is not optimal.

Identification of phenylpropanoids in methyl jasmonate treated Brassica rapa leaves using two-dimensional nuclear magnetic resonance spectroscopy.

Metabolic analysis showed a clear increase in phenylpropanoid levels in Brassica rapa leaves after treatment with methyl jasmonate. A fraction of phenylpropanoids was prepared by Diaion HP-20 and Sephadex LH-20 column chromatography after MeOH-water extraction. Even with these purification steps, isolation of each phenylpropanoid for structure elucidation is not easy due to the low levels in the plants (ca. 0.004%). A mixture was analyzed without further purification using HPLC-electrospray ionization mass spectrometry and NMR spectroscopy. Based on the NMR results including (1)H NMR, J-resolved, correlated spectroscopy (COSY), heteronuclear single quantum coherence (HSQC), and heteronuclear multiple bond correlation (HMBC) spectra, both (1)H and (13)C resonances of the compounds were obtained. Using these NMR data, five phenylpropanoids conjugated with malate were identified: 5-hydroxyferuloyl-, caffeoyl-, coumaroyl-, feruloyl-, and sinapoyl malate. Of the compounds, 5-hydroxyferuloyl malate is a new phenylpropanoid. In addition to the five constitutive phenylpropanoids bearing trans-configuration, their cis forms, which are believed to be artifacts formed in the course of extraction steps, were also identified in the fraction.

Pharmacokinetic behaviour of the chemoprotectants BNP7787 and mesna after an i.v. bolus injection in rats.

In preclinical studies, BNP7787 (disodium 2,2'-dithio-bis-ethane sulphonate), the disulphide form of mesna, has demonstrated selective protection against cisplatin-induced nephrotoxicity due to conversion into mesna inactivating toxic platinum species. Mesna (sodium 2-mercapto ethane sulphonate), however, can affect the antitumour activity of cisplatin, while BNP7787 does not interfere with the antitumour activity. To understand the difference in interference with cisplatin-induced antitumour activity between BNP7787 and mesna as well to characterise the selective nephroprotection by BNP7787, the pharmacokinetics of BNP7787 and mesna, each given i.v. 1000 mg x kg(-1), were determined in plasma, kidney, liver, red blood cells (RBC), skeletal muscle and tumour of Fischer rats bearing subcutaneously implanted WARD colon tumours. The following results were obtained: (1). high concentrations of BNP7787 and mesna were observed in the plasma and kidney after administration of BNP7787 or mesna, except for mesna in plasma after BNP7787 administration; (2). in all other sampled compartments, the AUC values of both compounds were at least 5.5-fold lower than the corresponding values in kidney; (3). the AUC of mesna in plasma after mesna administration was comparable to the AUC of mesna in kidney after a dose of BNP7787 that can completely prevent cisplatin-induced nephrotoxicity in rats; (4). the AUC of mesna in plasma was five-fold higher relative to the AUC of mesna following BNP7787 administration (P<0.01). In conclusion, the five-fold higher AUC of mesna in plasma after mesna administration and the fact that mesna is more reactive with (hydrated) cisplatin than its disulphide form BNP7787 represent a plausible explanation as to why mesna administration can reduce the antitumour activity of cisplatin. After BNP7787 administration, the distribution of BNP7787 and mesna was restricted to the kidney, which confirmed the selective protection of the kidney by BNP7787.

BNP7787, a novel protector against platinum-related toxicities, does not affect the efficacy of cisplatin or carboplatin in human tumour xenografts.

BNP7787 (2',2'-dithio-bis-ethane sulphonate sodium), a water-soluble disulphide, is chemically and mechanistically different from other sulphur-containing chemoprotective agents. Presently, BNP7787 is under investigation for its protective properties with regard to the side-effects of platinum compounds. In this study, we evaluated BNP7787, mesna and amifostine for their effects on the antitumour activity of platinum compounds. Continuous exposure to BNP7787 did not affect the antiproliferative effects of cisplatin or carboplatin, but the efficacy of both compounds was reduced in the presence of mesna in vitro in two human ovarian cancer cell lines. BNP7787 or amifostine combined with cisplatin or carboplatin given in standard schedules for the treatment of nude mice bearing well-established OVCAR-3 xenografts did not interfere with platinum-induced inhibition of tumour growth. Of interest, BNP7787 or amifostine co-administered with carboplatin was significantly more effective than carboplatin alone (P<0.01). In the presence of amifostine, doses of cisplatin and carboplatin could be safely increased by factors of 1.6 and 1.5, respectively. Unlike in a previous study of BNP7787 in tumour-bearing rats, BNP7787 did not protect against additional weight loss following treatment with higher doses of cisplatin in OVCAR-3-bearing mice. Pharmacokinetics of (mixed) disulphides including BNP7787 and extractable mesna in deproteinised plasma revealed a rapid disappearance of BNP7787 and an AUC(5-60) value of mesna 9-fold lower than that calculated after an equivalent dose of mesna by weight. We can conclude that BNP7787 does not interfere with the antitumour activity of platinum compounds in vitro and in vivo. Clinical trials are underway to evaluate the protection of normal tissues by BNP7787 when combined with cisplatin.

Organisation of signals involved in binocular perception and vergence control.

A novel type of dynamic random-dot stereogram (DRS) was used to study vergence movements and depth detection in response to temporal modulations of interocular correlation. Each DRS consisted of the repeated presentation of a pair of correlated images alternated by the presentation of a pair of uncorrelated images. The intervals of high (T(c)) and low (T(u)) correlation varied from 14 to 224 ms in steps of 14 ms. Depth detection and vergence responses behaved very different from each other as functions of T(c) and T(u). The different behaviours suggest that depth and vergence most likely result from independent streams of disparity processing. It is speculated that magnocellular layers process disparities that drive vergence and that a parvocellular stream of disparity processing is involved in depth perception. This suggestion is discussed in relation to recent findings on binocularly perceived direction and depth. The discussion leads to suggesting a headcentric organisation of signals involved in binocular perception and a retinal organisation of signals involved in vergence control.

Adaptation to disparity but not to perceived depth.

The purpose of the present study was to investigate whether adaptation can occur to disparity per se. The adapting stimuli were large random-dot patterns of which the two half-images were transformed such that the depth effects induced by the vertical transformations were nulled by horizontal transformations. Thus, the adapting stimuli were perceptually the same, whereas the disparity fields differed from each other. The adapting stimuli were presented for five minutes. During that period, the percept of a fronto-parallel surface did not change. After the adapting period, subjects perceived a thin untransformed strip as either slanted or curved depending on the adapting transformation. The thin strips provided negligible information about the vertical disparity field. In a forced-choice task we measured the amount of horizontal transformation that was required to null the acquired adaptation. We found that the amounts of horizontal transformation required to perceive the test strip fronto-parallel were significantly different from zero. We conclude that the visual system can adapt to disparity signals in the absence of a perceptual drive.

Strength of depth effects induced by three types of vertical disparity.

The goal of the present study is to compare the strengths of depth effects induced by different types of vertical disparity. We use a nulling task, in which the depth effects induced by vertical disparity are nulled by horizontal disparity. The advantage of this method is that it prevents cue conflicts from arising between disparity and other depth cues. The ratios between horizontal and vertical disparity that evoke the percept of a fronto-parallel stimulus vary per type of vertical disparity. The ratios determined for vertical scale and vertical quadratic mix (vertical scale with a horizontal gradient) vary strongly across subjects. The ratios for vertical shear are constant, since all subjects needed the same amount of horizontal and vertical shear to perceive a fronto-parallel plane. In these experiments, one conflict cannot be avoided, namely the conflict between vertical disparity and oculomotor signals. This conflict may cause differential weighting of vertical disparity and oculomotor signals, which could explain the individual differences. The different ratios for different types of vertical disparity suggest that weighting is specific for each type of vertical disparity and the associated oculomotor signal.

Is there an interaction between perceived direction and perceived aspect ratio in stereoscopic vision?

In monocular vision, the horizontal/vertical aspect ratio (shape) of a frontoparallel rectangle can be based on the comparison of the perceived directions of the rectangle's edges. In binocular vision of a typical three-dimensional scene (when occlusions are present), this is not the case: Frontoparallel rectangles would be perceived in a distorted fashion if an observer were to base perceived aspect ratio on the perceived directions of the rectangle's edges. We psychophysically investigated stereoscopically perceived aspect ratios of frontoparallel occluding and occluded rectangles for various distances and fixation depths. We found that observers did not perceive the distortions that would be predicted on the basis of the above-mentioned comparison of the perceived visual directions of the edges of the rectangle. Our results strongly suggest that the mechanism that determines perceived aspect ratio is dissociated from the mechanism that determines perceived direction. The consequences of the findings for the Kanizsa, Poggendorff, and horizontal/vertical illusions are discussed.

Perceived direction during monocular viewing is based on signals of the viewing eye only.

Perceived visual directions are derived from combining retinal signals and oculomotor signals. Up to now the general belief is that the oculomotor signals of the two eyes are first pooled before they become available for perception of depth and direction. In this sense the eyes are believed to act together as one unit known as the cyclopean eye. This study, however, shows that during monocular viewing in daylight conditions, the perceived directions of objects are indicated by their retinal locus in combination with the angular position of the viewing eye only, the angular position of the closed eye being irrelevant. This result indicates that in binocular vision the integration of left and right eye signals first occurs after retinal and oculomotor signals have been integrated of each eye separately. This conclusion challenges the prevailing concept of cyclopean vision and current views about stereoscopic depth perception.

Development of a panel of 15 human ovarian cancer xenografts for drug screening and determination of the role of the glutathione detoxification system.

OBJECTIVES: We have established a panel of 15 human ovarian cancer xenografts grown subcutaneously in the flank of the nude mouse. Similar to the clinic, the xenografts show differences in histological subtype and volume doubling time. We determined whether the panel is useful for drug screening by testing the sensitivity to six conventional anticancer agents. In addition, we investigated whether the glutathione detoxification system affects sensitivity to cisplatin and cyclophosphamide, major drugs in the treatment of ovarian cancer. METHODS: Mice bearing well-established tumors were treated at maximum tolerated doses as defined by a reversible weight loss up to 15% of their initial weight: cisplatin 5 mg/kg iv weekly x2, cyclophosphamide 150 mg/kg ip 2-weekly x2, doxorubicin 8 mg/kg iv weekly x2, hexamethylmelamine ip 150 mg/kg every other day x4, methotrexate ip 150 mg/kg weekly x2, and 5-fluorouracil 60 mg/kg ip weekly x4. Glutathione levels and the activities of three different glutathione-dependent enzymes were measured in untreated xenograft tissues. RESULTS: Growth inhibition >75% was reached for cisplatin in 40%, for cyclophosphamide in 27%, and for doxorubicin in 20% of the xenografts. Methotrexate and 5-fluorouracil did not induce growth inhibition of importance. Hexamethylmelamine showed >75% growth inhibition in 53% of the xenografts, which may have been caused by the favorable metabolism of the drug in mice when compared with that in patients. Glutathione levels varied 3.6-fold in the xenografts and did not show a relation with sensitivity to cisplatin, cyclophosphamide, or doxorubicin. No relation was found between the activities of glutathione S-transferase and glutathione peroxidase and the sensitivities to the three anticancer agents. Glutathione reductase activity, however, showed a weak, inverse relation with the efficacy of cisplatin and cyclophosphamide (r values of -0.55 and -0.58, respectively). CONCLUSIONS: The sensitivity to the six anticancer agents of our panel of 15 human ovarian cancer xenografts reflects the response rates known for similar drugs in ovarian cancer patients. In that respect, the panel may be useful for drug screening as well as studies on the relevance of drug resistance features in vivo. The various components of the glutathione detoxification system did not predict for primary drug resistance which confirms clinical data in ovarian cancer.

Comparison of external load compensation during rhythmic arm movements and rhythmic jaw movements in humans.

Experiments were performed on human elbow flexor and extensor muscles and jaw-opening and -closing muscles to observe the effect on rhythmic movements of sudden loading. The load was provided by an electromagnetic device, which simulated the appearance of a smoothly increasing spring-like load. The responses to this loading were compared in jaw and elbow movements and between expected and unexpected disturbances. All muscles showed electromyographic responses to unexpected perturbations, with latencies of approximately 65 ms in the arm muscles and 25 ms in the jaw. When loading was predictable, anticipatory responses started in arm muscles approximately 200 ms before and in jaw muscles 100 ms before the onset of loading. The reflex responses relative to the anticipatory responses were smaller for the arm muscles than for the jaw muscles. The reflex responses in the arm muscles were the same with unexpected and expected perturbations, whereas anticipation increased the reflex responses in the jaw muscles. Biceps brachii and triceps brachii showed similar sensory-induced responses and similar anticipatory responses. Jaw muscles differed, however, in that the reflex response was stronger in masseter than in digastric. It was concluded that reflex responses in the arm muscles cannot overcome the loading of the arm adequately, which is compensated by a large centrally programmed response when loading is predictable. The jaw muscles, particularly the jaw-closing muscles, tend to respond mainly through reflex loops, even when loading of the jaw is anticipated. The differences between the responses of the arm and the jaw muscles may be related to physical differences. For example, the jaw was decelerated more strongly by the load than the heavier arm. The jaw was decelerated strongly but briefly, <30 ms during jaw closing, indicating that muscle force increased before the onset of reflex activity. Apparently, the force-velocity properties of the jaw muscles have a stabilizing effect on the jaw and have this effect before sensory induced responses occur. The symmetrical responses in biceps and triceps indicate similar motor control of both arm muscles. The differences in reflex activity between masseter and digastric muscle indicate fundamental differences in sensory feedback to the jaw-closing muscle and jaw-opening muscle.

The influence of large scanning eye movements on stereoscopic slant estimation of large surfaces.

The results of several experiments demonstrate that the estimated magnitude of perceived slant of large stereoscopic surfaces increases with the duration of the presentation. In these experiments, subjects were free to make eye movements. A possible explanation for the increase is that the visual system needs to scan the stimulus with eye movements (which take time) before it can make a reliable estimate of slant. We investigated the influence of large scanning eye movements on stereoscopic slant estimation of large surfaces. Six subjects estimated the magnitude of slant about the vertical or horizontal axis induced by large-field stereograms of which one half-image was transformed by horizontal scale, horizontal shear, vertical scale, vertical shear, divergence or rotation relative to the other half-image. The experiment was blocked in three sessions. Each session was devoted to one of the following fixation strategies: central fixation, peripheral (20 deg) fixation and active scanning of the stimulus. The presentation duration in each of the sessions was 0.5, 2 or 8 s. Estimations were done with and without a visual reference. The magnitudes of estimated slant and the perceptual biases were not significantly influenced by the three fixation strategies. Thus, our results provide no support for the hypothesis that the time used for the execution of large scanning eye movements explains the build-up of estimated slant with the duration of the stimulus presentation.

Peripheral vision and oculomotor control during visual search.

The present study concerns the dynamics of multiple fixation search. We tried to gain insight into: (1) how the peripheral and foveal stimulus affect fixation duration; and (2) how fixation duration affects the peripheral target selection for saccades. We replicated the non-corroborating results of Luria and Strauss (1975) ('Eye movements during search for coded and uncoded targets', Perception and Psychophysics 17, 303-308) (saccades were selective), and Zelinsky (1996) (Using eye movements to assess the selectivity of search movements. Vision research 36(14), 2177-2187) (saccades were not selective), by manipulating the critical features for peripheral selection and discrimination separately. We found search to be more selective and efficient when the selection task was easy or when fixations were long-lasting. Remarkably, subjects did not increase their fixation durations when the peripheral selection task was more difficult. Only the discrimination task affected the fixation duration. This implies that the time available for peripheral target selection is determined mainly by the discrimination task. The results of the present experiment suggest that, besides the difficulty of the peripheral selection task, fixation duration is an important factor determining the selection of potential targets for eye movements.

Relation between torque history, firing frequency, decruitment levels and force balance in two flexors of the elbow.

By means of intramuscular electromyographic recordings, we studied the firing frequencies and recruitment/decruitment thresholds of individual motor units in two elbow flexors, the biarticular biceps brachii muscle and the monoarticular brachioradialis muscle. Subjects had to perform isometric contractions with increasing elbow flexion torque until a specific peak torque level was reached. The torque level was kept constant for 6 s during which firing frequencies were measured. Then the torque was decreased to a lower level and, after 3 s, firing frequencies were again measured for 6 s. By repeating this procedure, the torque level was decreased stepwise until the motor unit under study stopped firing. The last level before the unit stopped firing was considered to be the decruitment torque level. We measured the firing frequency at recruitment and decruitment, the torque-frequency relationship and the recruitment and decruitment torque thresholds after various levels of peak torque. In the biceps, both the firing frequencies at a specific torque level and the decruitment torque level itself were independent of the peak torque. In the brachioradialis, however, firing frequencies at a specific torque level decreased and decruitment torque levels increased after subjects generated higher peak torques. Thus, in this muscle firing frequencies as well as decruitment thresholds show hysteresis effects. The result indicates a shift of force from the brachioradialis muscle during recruitment to the biceps muscle during decruitment. This shift is smaller than was concluded from previous studies in which decruitment threshold levels for the brachioradialis muscle were assumed to be independent of force history. Moreover, we found that in both muscles decruitment firing frequencies were lower than recruitment frequencies and they were independent of the peak torque level. In order to analyse the effect of the peak torque level on the distribution of force over the two muscles, we performed a model study in which we simulated the activation-frequency relation of two elbow flexors: a biceps-like and brachioradialis-like muscle, each contributing equally to the elbow torque during recruitment. In addition, we analysed how the different behaviour of the biceps and the brachioradialis during decruitment alters their contribution to the total torque production and how this redistribution is caused. The model study shows that the shift in contribution to the total torque is not constant during the relaxation phase and is not caused by a simple mechanism like a shift of activation from one muscle to another. Furthermore, changes limited to the muscle in which hysteresis is present do not seem to be sufficient to explain the experimental results.

Characterization of human soft-tissue sarcoma xenografts for use in secondary drug screening.

We have established ten transplantable human soft-tissue sarcoma (STS) xenografts grown as subcutaneous tumours in the nude mouse. Nine xenografts originated from patients that needed chemotherapy in the course of their disease. The xenografts were tested for their sensitivity to maximum tolerated doses of five anti-cancer agents. Growth of treated tumours was expressed as a percentage of control tumour growth and a growth inhibition > 75% was measured for doxorubicin in 20% of the STS xenografts, for cyclophosphamide in 30%, for ifosfamide in 20%, for vincristine in 20%, whereas etoposide was not effective in the STS xenografts. In three out of ten STS xenografts MDR1 mRNA was detectable, but this was not related to the resistance against doxorubicin, vincristine or etoposide. Topoisomerase IIalpha mRNA expression levels did not reflect sensitivity to doxorubicin or etoposide. In all STS tissues, however, these levels were lower than topoisomerase IIalpha mRNA in a drug-sensitive human ovarian cancer xenograft. Glutathione concentrations and the activities of glutathione S-transferase, glutathione peroxidase and glutathione reductase were not related to resistance against the alkylating agents or doxorubicin. Of interest, in all STS tissues, glutathione S-transferase pi was the predominant isoenzyme present. In conclusion, chemosensitivity of the STS xenografts reflects clinical response rates in phase II trials on the same compounds in adult STS patients. Relatively low levels of topoisomerase IIalpha mRNA may partly account for intrinsic resistance against, for example, doxorubicin. Additional factors must contribute to moderate responsiveness to alkylating agents.

The efficacy of the anthracycline prodrug daunorubicin-GA3 in human ovarian cancer xenografts.

The prodrug N-[4-(daunorubicin-N-carbonyl-oxymethyl)phenyl] O-beta-glucuronyl carbamate (DNR-GA3) was synthesized for specific activation by human beta-glucuronidase, released in necrotic areas of tumour lesions. In vitro, DNR-GA3 was 18 times less toxic than daunorubicin (DNR) and the prodrug was completely activated to the parent drug by human beta-glucuronidase. The maximum tolerated dose of DNR-GA3 in nude mice bearing s.c. human ovarian cancer xenografts was 6-10 times higher than that of DNR. The prodrug was cleared more rapidly from the circulation (elimination t1/2 = 20 min) than the parent drug (elimination t1/2 = 720 min). The anti-tumour effects of DNR-GA3 and DNR were investigated in four different human ovarian cancer xenografts OVCAR-3, FMa, A2780 and MRI-H-207 at a mean tumour size between 100 and 200 mm3. In three out of four of these tumour lines, the prodrug given i.v. at the maximum tolerated dose ranging from 150 to 250 mg kg(-1) resulted in a maximum tumour growth inhibition from 82% to 95%. The standard treatment with DNR at a dose of 8 mg kg(-1) given i.v. weekly x 2 resulted only in a maximum tumour growth inhibition from 40% to 47%. Tumour line FMa did not respond to DNR, nor to DNR-GA3. Treatment with DNR-GA3 was also given to mice with larger tumours that would contain more necrosis (mean size 300-950 mm3). The specific growth delay by DNR-GA3 was extended from 2.1 to 4.4 in OVCAR-3 xenografts and from 4.4 to 6.0 in MRI-H-207 xenografts. Our data indicate that DNR-GA3 is more effective than DNR and may be especially of use for treatment of tumours with areas of necrosis.

A computational model of depth perception based on headcentric disparity.

It is now well established that depth is coded by local horizontal disparity and global vertical disparity. We present a computational model which explains how depth is extracted from these two types of disparities. The model uses the two (one for each eye) headcentric directions of binocular targets, derived from retinal signals and oculomotor signals. Headcentric disparity is defined as the difference between headcentric directions of corresponding features in the left and right eye's images. Using Helmholtz's coordinate systems we decompose headcentric disparity into azimuthal and elevational disparity. Elevational disparities of real objects are zero if the signals which contribute to headcentric disparity do not contain any errors. Azimuthal headcentric disparity is a 1D quantity from which an exact equation relating distance and disparity can be derived. The equation is valid for all headcentric directions and for all binocular fixation positions. Such an equation does not exist if disparity is expressed in retinal coordinates. Possible types of errors in oculomotor signals (six) produce global elevational disparity fields which are characterised by different gradients in the azimuthal and elevational directions. Computations show that the elevational disparity fields uniquely characterise both the type and size of the errors in oculomotor signals. Our model uses a measure of the global elevational disparity field together with local azimuthal disparity to accurately derive headcentric distance throughout the visual field. The model explains existing data on whole-field disparity transformations as well as hitherto unexplained aspects of stereoscopic depth perception.