Differential Latency Research Articles

Self-tuning architecture enabling bidirectional transceiver normalization and low differential latency

Self-tuning architecture enabling bidirectional transceiver normalization and low differential latency

Differential Latencies Sculpt the Time Course of Contextual Effects on Spatial Perception.

The ability to judge an object's orientation with respect to gravitational vertical relies on an egocentric reference frame that is maintained using not only vestibular cues but also contextual cues provided in the visual scene. Although much is known about how static contextual cues are incorporated into the egocentric reference frame, it is also important to understand how changes in these cues affect perception, since we move about in a world that is itself dynamic. To explore these temporal factors, we used a variant of the rod-and-frame illusion, in which participants indicated the perceived orientation of a briefly flashed rod (5-msec duration) presented before or after the onset of a tilted frame. The frame was found to bias the perceived orientation of rods presented as much as 185 msec before frame onset. To explain this postdictive effect, we propose a differential latency model, where the latency of the orientation judgment is greater than the latency of the contextual cues' initial impact on the egocentric reference frame. In a subsequent test of this model, we decreased the luminance of the rod, which is known to increase visual afferent delays and slow decision processes. This further slowing of the orientation judgment caused the frame-induced bias to affect the perceived orientation of rods presented even further in advance of the frame. These findings indicate that the brain fails to compensate for a mismatch between the timing of orientation judgments and the incorporation of visual cues into the egocentric reference frame.

Lentiviral Nef Proteins Differentially Govern the Establishment of Viral Latency.

Despite the clinical importance of latent human immunodeficiency virus type 1 (HIV-1) infection, our understanding of the biomolecular processes involved in HIV-1 latency control is still limited. This study was designed to address whether interactions between viral proteins, specifically HIV Nef, and the host cell could affect latency establishment. The study was driven by three reported observations. First, early reports suggested that human immunodeficiency virus type 2 (HIV-2) infection in patients produces a lower viral RNA/DNA ratio than HIV-1 infection, potentially indicating an increased propensity of HIV-2 to produce latent infection. Second, Nef, an early viral gene product, has been shown to alter the activation state of infected cells in a lentiviral lineage-dependent manner. Third, it has been demonstrated that the ability of HIV-1 to establish latent infection is a function of the activation state of the host cell at the time of infection. Based on these observations, we reasoned that HIV-2 Nef may have the ability to promote latency establishment. We demonstrate that HIV-1 latency establishment in T cell lines and primary T cells is indeed differentially modulated by Nef proteins. In the context of an HIV-1 backbone, HIV-1 Nef promoted active HIV-1 infection, while HIV-2 Nef strongly promoted latency establishment. Given that Nef represents the only difference in these HIV-1 vectors and is known to interact with numerous cellular factors, these data add support to the idea that latency establishment is a host cell-virus interaction phenomenon, but they also suggest that the HIV-1 lineage may have evolved mechanisms to counteract host cell suppression. IMPORTANCE Therapeutic attempts to eliminate the latent HIV-1 reservoir have failed, at least in part due to our incomplete biomolecular understanding of how latent HIV-1 infection is established and maintained. We here address the fundamental question of whether all lentiviruses actually possess a similar capacity to establish latent infections or whether there are differences between the lentiviral lineages driving differential latency establishment that could be exploited to develop improved latency reversal agents. Research investigating the viral RNA/DNA ratio in HIV-1 and HIV-2 patients could suggest that HIV-2 indeed has a much higher propensity to establish latent infections, a trait that we found, at least in part, to be attributable to the HIV-2 Nef protein. Reported Nef-mediated effects on host cell activation thus also affect latency establishment, and HIV-1 vectors that carry different lentiviral nef genes should become key tools to develop a better understanding of the biomolecular basis of HIV-1 latency establishment.

Motion extrapolation in the flash-lag effect depends on perceived, rather than physical speed

In the flash-lag effect (FLE), a flash in spatiotemporal alignment with a moving object is misperceived as lagging behind the moving object. One proposed explanation for this illusion is based on predictive motion extrapolation of trajectories. In this interpretation, the diverging effects of velocity on the perceived position of the moving object suggest that FLE might be based on the neural representation of perceived, rather than physical, velocity. By contrast, alternative explanations based on differential latency or temporal averaging would predict that the FLE does not rely on such a representation of perceived velocity. Here we examined whether the FLE is sensitive to illusory changes in perceived speed that result in changes to perceived velocity, while physical speed is constant. The perceived speed of the moving object was manipulated using revolving wedge stimuli with variable pattern textures (Experiment 1) and luminance contrast (Experiment 2). The motion extrapolation interpretation would predict that the changes in FLE magnitude should correspond to the changes in the perceived speed of the moving object. In the current study, two experiments demonstrated that perceived speed and FLE magnitude increased in the dynamic pattern relative to the static pattern conditions, and that the same effect was found in the low contrast compared to the high contrast conditions. These results showed that manipulations of texture and contrast that are known to alter judgments of perceived speed also modulate perceived position. We interpret this as a consequence of motion extrapolation mechanisms and discuss possible explanations for why we observed no cross-effect correlation.

A Prediction-Based Model for Consistent Adaptive Routing in Back-Bone Networks at Extreme Situations

To reduce congestion, numerous routing solutions have been proposed for backbone networks, but how to select paths that stay consistently optimal for a long time in extremely congested situations, avoiding the unnecessary path reroutings, has not yet been investigated much. To solve that issue, a model that can measure the consistency of path latency difference is needed. In this paper, we make a humble step towards a consistent differential path latency model and by predicting base on that model, a metric Path Swap Indicator (PSI) is proposed. By learning the history latency of all optional paths, PSI is able to predict the onset of an obvious and steady channel deterioration and make the decision to switch paths. The effect of PSI is evaluated from the following aspects: (1) the consistency of the path selected, by measuring the time interval between PSI changes; (2) the accuracy of the channel congestion situation prediction; and (3) the improvement of the congestion situation. Experiments were carried out on a testbed using real-life Abilene traffic datasets collected at different times and locations. Results show that the proposed PSI can stay consistent for over 1000 s on average, and more than 3000 s at the longest in our experiment, while at the same time achieving a congestion situation improvement of more than 300% on average, and more than 200% at the least. It is evident that the proposed PSI metric is able to provide a consistent channel congestion prediction with satisfiable channel improvement at the same time. The results also demonstrate how different parameter values impact the result, both in terms of prediction consistency and the congestion improvement.

Midbrain control of breathing and blood pressure: The role of periaqueductal gray matter and mesencephalic collicular neuronal microcircuit oscillators.

Neural circuitry residing within the medullary ventral respiratory column nuclei and dorsal respiratory group interact with the Kölliker-Fuse and medial parabrachial nuclei to generate the corebreathing rhythm and patternduring resting conditions. Triphasic eupnea consists of inspiratory [I], post-inspiratory [post-I], and late-expiratory [E2] phases. Mesencephalic zones exert modulatory influences upon respiratory rhythm-generating circuitry, sympathetic oscillators, and parasympathetic nuclei. The earliest evidence supporting the existence of midbrain control of breathing derives from studies conducted by Martin and Booker in 1878. These authors demonstrated electrical stimulation of the deep layers of themesencephalic colliculi in the rabbitaugmented ventilation and sequentially elicited chest wall tremors and tetany. Investigations performed during the past several decadeswould demonstrate stimlation of distributed zones within the midbrain reticular formation elicits starkly disparate effects upon respiratory phase switching. Schmid, Böhmer, and Fallert demonstrated electrical stimulation of the nucleus rubreand emanating axon bundles alternately elicits or inhibits the activity of medullary expiratory- or inspiratory-related units and phrenic nerve discharge with differential latency. A series of studies would later indicate the red nucleus mediates hypoxic ventilatory depression. Periaqueductal gray matter neurons exhibit extensive afferent and efferent interconnectivity with suprabulbar, brainstem, and spinal cord zones aptly positioning these units to modulate breathing, autonomic outflow, nociception locomotion, micturtion, and sexual behavior.Experimental stimulatory activation of the tectal colliculi and periaqueductal gray matter via electrical current or glutamate, D,L-homocysteinic acid, or bicuculline microinjections coordinately modulates neuromotor inspiratory bursting frequency and amplitude and discharge of pre-Bötzinger complex, ventrolateral medullary late-I and post-I, and ventrolateral nucleus tractus solitarius decrementing early-I and augmenting and decrementing late-I neurons, elicits expiratory outflow and vocalization, and blunt the Hering-Breuer reflex in unanesthetzed decerebrate and anesthetized preprations of the cat and rat. Stimulation of the mesencephalic colliuli or dorsal divisions of the PAG potently amplifes renal sympathetic neural efferent activity, dynamic arterial pressure magnitude, and myocardial contraction frequency and elicits various behavioral defense responses. Elicited physiological effects exhibit extensive locoregional heterogeneity and variably enlist requisite contributions from the dorsomedial hypothalamus and/or lateral parabrachial nuclei. Stimulation of the dorsal mesencephalon occasionally elicits dynamic increases of arterial pressure magnitude exhibiting prominent oscillatory variability coherent with phrenic nerve discharge, perhaps by generating intra-neuraxial hysteresis, serving to intermittently deliver blood to organ vascular beds under high pressure in order to prevent organ edema, microcirculatory dysfunction, and downregulation of vascular smooth muscle alpha adrenergic receptors. Chemosensitive mesencephalic caudal raphéunits and projections of hypoxia-sensitive units in the caudal hypothalamus to the periaqueductal gray matter may imply the existence of a diencephalo-smesencephalic chemosensitive network modulating breathing and sympathetic discharge.

Effects of football practice on blink reflex parameters in Division I football athletes

ObjectiveThe objective was to access the effects of football practice sessions on blink reflex parameters using the Eyestat.BackgroundOur laboratory has utilized a potential objective measure to identify concussions. This technology, called Eyestat, is a noninvasive diagnostic tool measuring changes in blink reflex parameters. Prior research cited significant differences in various blink reflex parameters between active play, concussion, and baseline; however, the number of subjects for the active play population was small (N = 10). Thus, the purpose of this study was to identify blink reflex parameters during football practice, providing outcomes potentially helpful with its use for a concussed population.Design/MethodsForty-seven Division I male football players between the ages of 18-22 were evaluated on multiple sessions during a 2 week period of football practices. During various points of the practice, subjects completed the blink test and had their heart rate assessed. During the blink test, subjects placed their face against the apparatus, which directed a puff of air to the corner of the subject’s eye to stimulate the blink. Five puffs were administered in a random fashion over a 20 second period in which videography captured and recorded the blink.ResultsResults of the study found significant differences in latency (p = 0.0000), time under the threshold (p = 0.0176), oscillations (p = 0.0217) and excursion (p = 0.0003), but no significant differences in differential latency (p = 0.0626). Average heart rate was 125 BPM, with a minimum of 72 BPM and maximum of 172 BPM. The results of this study correlate with prior research in latency, time under the threshold and excursions and support the changes in blink reflex parameters after football practice.ConclusionsFuture studies need to assess if changes occur with individual physical activity or is it related only to the practice of this sport.

Neurodynamics of time consciousness: An extensionalist explanation of apparent motion and the specious present via reentrant oscillatory multiplexing.

This paper situates an original model of reentrant oscillatory multiplexing within the philosophy of time consciousness to argue for an extensionalist theory of the specious present. I develop a detailed differential latency model of apparent motion to show how the ordinality of experiential content is isomorphic to the ordinality of relevant brain processes. I argue that the theory presented has resources to account for other key features of the specious present, including the representational discreteness between successive conscious moments as well as the phenomenological continuity between them. This work not only shows the plausibility of an extensionalist philosophical theory, it also illustrates the utility of differential latency views in squaring temporal illusions with empirically supported neurodynamics.

Distinct mechanisms of temporal binding in generalized and cross-modal flash-lag effects

It remains unknown how the brain temporally binds sensory data across different modalities and attributes to create coherent perceptual experiences. To address this question, we measured what we see at the time we experience an event using a generalized version of the flash-lag effect (FLE) for combinations of visual attribute (bar orientation, face orientation, or face identity) and probe modality (visual or auditory). We asked participants to judge the content of rapidly and serially presented images seen at the same time as a briefly presented visual (flash) or auditory (click) probe and estimated the “time windows” contributing to decisions using reverse correlation analysis. We also used displays in which the visual attribute of a stimulus continuously changed and measured FLEs around abrupt flip in change direction and at the initiation and termination of a sequence. We consistently found clear latency-difference effects, which depended on visual attribute for the visual probe but did not for the auditory probe. The intra-modal FLE can be explained in terms of differential latency and temporal integration, but the cross-modal FLE is suggested to operate via a distinct mechanism; the content of a successive visual stream experienced after the awareness of a click is interpreted as simultaneous with the click.

Faster processing of moving compared with flashed bars in awake macaque V1 provides a neural correlate of the flash lag illusion.

When the brain has determined the position of a moving object, because of anatomical and processing delays the object will have already moved to a new location. Given the statistical regularities present in natural motion, the brain may have acquired compensatory mechanisms to minimize the mismatch between the perceived and real positions of moving objects. A well-known visual illusion-the flash lag effect-points toward such a possibility. Although many psychophysical models have been suggested to explain this illusion, their predictions have not been tested at the neural level, particularly in a species of animal known to perceive the illusion. To this end, we recorded neural responses to flashed and moving bars from primary visual cortex (V1) of awake, fixating macaque monkeys. We found that the response latency to moving bars of varying speed, motion direction, and luminance was shorter than that to flashes, in a manner that is consistent with psychophysical results. At the level of V1, our results support the differential latency model positing that flashed and moving bars have different latencies. As we found a neural correlate of the illusion in passively fixating monkeys, our results also suggest that judging the instantaneous position of the moving bar at the time of flash-as required by the postdiction/motion-biasing model-may not be necessary for observing a neural correlate of the illusion. Our results also suggest that the brain may have evolved mechanisms to process moving stimuli faster and closer to real time compared with briefly appearing stationary stimuli. NEW & NOTEWORTHY We report several observations in awake macaque V1 that provide support for the differential latency model of the flash lag illusion. We find that the equal latency of flash and moving stimuli as assumed by motion integration/postdiction models does not hold in V1. We show that in macaque V1, motion processing latency depends on stimulus luminance, speed and motion direction in a manner consistent with several psychophysical properties of the flash lag illusion.

The flash-lag effect and the flash-drag effect in the same display

Visual motion distorts the perceived position of a stimulus. In the flash-drag effect (FDE), the perceived position of a flash appears to be shifted in the direction of nearby motion. In the flash-lag effect (FLE), a flash adjacent to a moving stimulus appears to lag behind. The FLE has been explained by several models, including the differential latency hypothesis, that a moving stimulus has a shorter processing latency than a flash does. The FDE even occurs when the flash is presented earlier than the moving stimulus, and it has been discussed whether this temporal property can be explained by the differential latency model. In the present study, we simultaneously quantified the FDE and FLE using the random jump technique (Murakami, 2001b) and compared their temporal properties. While the positional offset between a randomly jumping stimulus and a flashed stimulus determined the FLE, a drifting grating appeared next to the flash at various stimulus-onset asynchronies to induce the FDE. The grating presented up to 200 ms after the flash onset induced the FDE, whose temporal tuning was explained by a simple convolution model incorporating stochastic fluctuations of differential latency estimated from the FLE data and a transient-sustained temporal profile of motion signals. Thus, a common temporal mechanism to compute the stimulus position in reference to surrounding stimuli governs both the FDE and the FLE.

Investigating Behaviour and Face Encoding in a Hypothetical Real-World Social Contract: Handwashing in Hazardous Health Settings

Investigations into the evolutionary origins of human cognition has shown that individuals’ memory for others is influenced by the latter’s behaviour in social contracts. Such research is primarily based on hypothetical or more abstract forms of social contracts, whereas an application of this knowledge to everyday health behaviours can be of great value. To address this, the current study investigated whether participants who were asked to imagine themselves in a hypothetical hazardous health scenario showed differential response sensitivity (d’) and latency (RT) to faces of hospital staff tagged with contrasting hand hygiene before touching patients: clean hands, dirty hands, or unknown hand-washing behaviour (control). The test used a two alternative forced-choice (2AFC: “old/new”) face recognition paradigm. The findings showed that d’ to dirty and clean hands was similar, but higher than for controls. Moreover, d’ was not affected by the occupation of hospital staff (nurses vs porters). The absence of memory gains towards clean or dirty hands points to the need for new strategies to remind patients to observe (and remember) the hand hygiene of others when exposed to hazardous health environments.

Differential latency toward (–)-epicatechin and catechol mediated by avocado mesocarp polyphenol oxidase (PPO)

The polyphenol oxidase (PPO) metabolism of the endogenous substrate (–)-epicatechin has been correlated with browning in avocados and other fruit. Although total PPO activity declined during ripening in the avocado mesocarp, a selective retention of high electrophoretic mobility isoforms was observed during ripening. Avocado PPO was virtually inactive toward (–)-epicatechin without the addition of an activator such as sodium dodecyl sulfate. In contrast, PPO was active toward catechol, an exogenous substrate, in the absence of an activator. Low concentrations of the free fatty acids oleic acid, linoleic acid, and arachidonic acid were effective activators of (–)-epicatechin oxidation in vitro. The data suggest that these endogenous free fatty acids may play a role in the PPO-mediated browning of avocado fruit in vivo.

New Twists for an Old Turning Illusion

A Vernier-offset illusion induced by rotating lines, introduced by Matin et al (1976 Perception & psychophysics 20 138-142) was re-examined using onset, offset, and reverse trajectories inspired by flash-lag illusion research, with both Vernier and alignment-with-vertical judgments being recorded. The pattern of illusions found was generally in agreement with a differential latency of stimulus ends account described by those authors, although certain variants of modern spatial projection theories, and a differential latency of attribute account, could also accommodate much of the data.

Majority-rule opinion dynamics with differential latency: a mechanism for self-organized collective decision-making

Collective decision-making is a process whereby the members of a group decide on a course of action by consensus. In this paper, we propose a collective decision-making mechanism for robot swarms deployed in scenarios in which robots can choose between two actions that have the same effects but that have different execution times. The proposed mechanism allows a swarm composed of robots with no explicit knowledge about the difference in execution times between the two actions to choose the one with the shorter execution time. We use an opinion formation model that captures important elements of the scenarios in which the proposed mechanism can be used in order to predict the system’s behavior. The model predicts that when the two actions have different average execution times, the swarm chooses with high probability the action with the shorter average execution time. We validate the model’s predictions through a swarm robotics experiment in which robot teams must choose one of two paths of different length that connect two locations. Thanks to the proposed mechanism, a swarm made of robot teams that do not measure time or distance is able to choose the shorter path.

Differential proviral latency of the HIV-1 subtypes B and AE

The current HIV-1 pandemic is caused by at least nine subtypes (termed A through K) and an increasing number of recombinant forms. There has been a large skew in research focus on subtype B, which is the most prevalent subtype in the Western world. We study the transcriptional promoter in the long terminal repeat (LTR). Each subtype has a specific LTR promoter configuration and even minor changes in the transcription factor-binding sites (TFBS) or their rearrangement can have a significant impact on cell tropism and pathogenicity. For the HIV-1 subtypes, the LTR promoter variation could contribute to differences in proviral latency. Such differences in latency properties may have an impact on the establishment of viral reservoirs and the inability to clear the virus by therapeutic intervention. Latency remains a formidable barrier towards virus eradication as therapeutic attempts to purge these reservoirs have been unsuccessful. The pool of latent proviruses is established early during infection and forms a steady source of proviral DNA that can last a lifetime in infected individuals. We have demonstrated previously that there are differences in proviral latency properties between the subtypes, which are determined in part by the LTR promoter. Most interesting was the observation that subtype AE combined higher basal transcription (-Tat) with reduced proviral latency. The naturally occurring replacement of an NFkB for GABP site was partially responsible for this AE-specific latency phenotype. Another transcription factor that may contribute to the increased basal transcription of subtype AE is AP-1, which is present in subtype AE but absent in subtype B. We generated luciferase constructs with and without this AP-1 site in both subtype LTR backbones to determine the influence of AP-1. The luciferase constructs contain the core promoter region with all major TFBS (e.g. NFkB and Sp1 sites). Results obtained with these reporter constructs will be presented.

The flash-lag effect in random motion reveals distributed differential latency between the flash and motion

The flash-lag effect in random motion reveals distributed differential latency between the flash and motion

Simple differential latencies modulate, but do not cause the flash-lag effect

When a brief static flash is presented in physical alignment with a moving target, the position of the flash can seem to lag behind that of the moving target. Various explanations exist. One of the most popular is the differential latency hypothesis. This assumes that neural latencies for moving stimuli are shorter than those for static stimuli. Accordingly, the flash lag would occur because perception is temporally fragmented, with moving stimuli seen before static. To test this, observers were asked to make different judgments concerning the same stimulus. Observers either judged if color changes in moving and static stimulus sections were synchronous, or whether the different stimulus sections were aligned at the time of a color change. If the flash-lag were driven by a simple differential latency, we would expect both judgments to be marked by a temporal advantage for moving stimuli. Our results suggest the contrary, as only the later judgment was marked by a flash-lag effect. The apparent timing of moving and static color changes was veridical. However, when we introduced a systematic differential latency, by modulating image contrast, both judgments were affected. Our data therefore suggest that a simple differential can modulate flash-lag type effects, but they do not cause the phenomenon.

The Effects of Foot Position on the Performance of the Sit-To-Stand Movement With Chronic Stroke Subjects

Camargos AC, Rodrigues-de-Paula-Goulart F, Teixeira-Salmela LF. The effects of foot position on the performance of the sit-to-stand movement with chronic stroke subjects. Objective To investigate the effects of different foot positions during the sit-to-stand (STS) movements with stroke subjects. Design Cross-sectional. Setting Research laboratory. Participants Twelve chronic stroke subjects (N=12). Interventions Not applicable. Main Outcome Measures Differential latency and electromyography (EMG) activity of the tibialis anterior, soleus, quadriceps, and hamstring muscles of the affected leg as well as the movement time, time of seat-off, weight symmetry, and rising index were obtained while the subjects performed the STS movements by using 4 different strategies: spontaneous; symmetric; asymmetric-1, with the affected foot behind; and asymmetric-2, with the unaffected foot behind. Results Compared with the spontaneous strategy, the soleus showed the greatest differential latency in the asymmetric-2 strategy, the hamstrings had lower EMG activity in the symmetric strategy, and the movement time was greater in the asymmetric strategies. Conclusions The asymmetric 2 strategy appeared to be the least favorable, whereas the spontaneous and the symmetric strategies appeared to be more favorable in improving the STS performance. Based on these findings, allowing the subjects to adopt the spontaneous strategy or training of the symmetric strategy could result in greater benefits for subjects with higher chronicity and higher functional levels, such as those evaluated in the present study.

Time-dependent gene expression changes in a xenograft model of docetaxel cytotoxicity.

Abstract Abstract #2009 Background: The antitumor effects of docetaxel primarily result from mitotic arrest with impaired cell proliferation. However, the key molecular pathways affected by this agent are largely unknown, and alternative mechanisms of action are likely. Knowledge of these pathways and mechanisms will guide the rational design of more effective treatment schedules and drug combinations. We hypothesize that the molecular analysis of treated human breast cancer xenografts will allow for an evaluation of time-dependent alterations in the expression of genes involved in key cell processes related to docetaxel cytotoxicity.
 Methods: Gene expression profiles were generated from MDA-MB-231 breast cancer xenografts after a single intravenous dose of docetaxel. Tumors were harvested at 1, 6, 12, and 24 hours (hr) after drug administration; a control group of untreated tumors (0hr) was included. RNA was extracted, assessed for concentration and quality, and used to generate probes for hybridization to the Affymetrix Human U133A oligonucleotide gene chip. Gene expression levels were explored with MAS 5.0 software and in-house algorithms. Subsequent data analysis included cross-experiment normalization, differential gene selection, gene clustering, and peak-time latency analysis. Consistency between the in-house in vivo dataset and a public in vitro dataset (Oncogene. 26:2902) was investigated.
 Results: 5087 responsive genes were selected using both SAM and EDGE. Among these genes, 3009 were down-regulated and 190 were up-regulated by at least 2-fold. Compared with 0h, the most significant changes in gene expression took place 6h after drug administration (2023 down-regulated and 655 up-regulated genes). Gene clustering revealed the sequence of up-regulation or down-regulation of different gene groups. Apoptosis-related genes and cell cycle-related genes in various stages showed different time latency patterns. For example, most of the M phase genes (total of 65 from Gene Ontology) were down-regulated 6h and 12h after docetaxel treatment and recovered by 24h. In addition, 1489 of 3009 down-regulated genes and 55 of 190 up-regulated genes were found in a public in vitro dataset; these datasets share 282 down-regulated genes (18.9%) and 17 up-regulated genes (30.9%).
 Discussion: Analysis of serial gene expression changes in docetaxel sensitive breast cancer xenografts demonstrates that time-dependent changes in specific cell processes occur. These findings will be expanded to distinguish between early and late molecular mechanisms of docetaxel responsiveness. A parallel xenograft model of docetaxel nonresponsiveness is also under investigation. In this way, time-dependent pathways will be defined that will include predictive biomarkers and lead to the development of novel agents to overcome resistance or enhance sensitivity to docetaxel, one of the most effective agents available for the treatment of breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2009.