Biomedical subjects
Publications and source records attributed to D L Wright.
The ring-opening cross-metathesis of oxabicyclo[3.2.1]octene derivatives provides a convenient method for preparing differentially substituted 4-pyrones. The major competing reaction is the ring-opening metathesis polymerization of the bridged olefin. Studies on this reaction have shown that substituents on the bicyclic alkene can have a dramatic influence on the competing reactions. [reaction: see text]
OBJECTIVE: To investigate the use of donated gametes for the production of human embryonic stem cell lines. DESIGN: Basic research study. SETTING: Assisted Reproductive Technology (ART) program at an academic institution. PATIENT(S): Consenting oocyte and sperm donors. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Oocytes were aspirated from oocyte donors (n = 12) and inseminated with frozen-thawed donor (n = 2) sperm followed by culture of embryos to day 5 or 6 in sequential media. The inner cell masses of expanded blastocysts were isolated using immunosurgery and cultured for 4-11 days on irradiated primary mouse embryonic fibroblasts (PMEFs). Viable cell colonies were passed every 7-10 days onto fresh PMEFs in the presence of leukemia inhibitory factor (0.1 microg/mL) and evaluated for appropriate cell surface markers. RESULT(S): Immunosurgery of 40 blastocysts resulted in the culture of 18 inner cell masses, which have produced three cell lines. One of these cell lines has been shown to stain positive for alkaline phosphatase and stage-specific embryonic antigen (SSEA)-4 and negative for SSEA-1, express telomerase activity, and produce hCG when allowed to differentiate. CONCLUSION(S): These findings demonstrate that the future production of human embryonic stem cell lines for therapeutic use is possible with the use of donated gametes. Many ethical issues were considered before the initiation of this study, and it was our goal to ensure that both oocyte and sperm donors understood the nature and purpose of the research before their participating in the study.
Random practice has been reported to demand greater time for movement preparation during acquisition than blocked practice. The present study revealed that this could be attributed to a more complete engagement of the motor programming process during random practice. This cost, however, was localized to the motor programming subprocess that S. T. Klapp (1995) associated with organizing the internal structure of a movement chunk rather than an alternative subprocess responsible for organizing movement chunks into the correct serial order. The more thorough employment of motor programming during acquisition by random practice participants resulted in a more efficient use of this planning operation during retention, as well as more accurate movement reproduction. These data support the claim that practice conditions high in contextual interference support improvements in both movement preparation and memory strength.
In 3 experiments, the authors used a precuing protocol to examine the nature and cost of programming and the subsequent reprogramming of a movement's relative time and overall duration. Initial programming followed a fixed-order specification; knowledge of the necessary relative time was required before information regarding overall duration could be used in a manner that expedited response planning. In the case of reprogramming, however, when a modification had to be made in either the relative time or overall duration of the anticipated and already-prepared response, performers chose to completely reprogram the entire response. Complete reprogramming occurred even when the performer had correctly prepared the higher order relative-time component and only had to modify the overall duration of the movement. The data indicate that organizing movement timing before movement initiation is accomplished in a fundamentally different manner depending on whether the movement is being initially compiled or modified.
The authors conducted the present experiments to resolve the discrepancy between studies in which relative-timing learning has been found to be enhanced by consistent practice conditions and contextual interference experiments in which relative-timing learning has been found to be enhanced more by random practice than by blocked practice. There were 40 participants in Experiment 1 and 48 in Experiment 2. The results of Experiment 1 extended previous findings: The learning of the relative-timing pattern was systematically enhanced by the degree to which the practice conditions promoted movement consistency (constant > blocked > serial > random). Experiment 2 provided evidence that the discrepancy between the relative-timing effects in the 2 groups of studies was a product of the way in which relative-timing goals and feedback were presented. When the feedback was presented as segment times, random practice resulted in generally more stable relative-timing patterns during acquisition than blocked practice did. Thus, in both experiments, the learning of the relative-timing pattern was enhanced by more stable relative-timing conditions during acquisition. Absolute-timing learning, as indexed by the transfer tests, was enhanced by serial or random practice as compared with constant or blocked practice, and was relatively unaffected by feedback conditions directed at the relative-timing pattern. In terms of motor programming theory, those findings are taken as additional evidence for the disassociation of memories supporting generalized motor program (GMP) performance, as indexed by relative timing, and parameter performance, as indexed by absolute timing.
Blocked practice engenders more trial-to-trial response stability, which is thought to be crucial for developing the generalized motor program (GMP) but not parameter learning (Lai, Shea, Wulf, & Wright, 2000). It was hypothesized that reducing the difficulty of the GMP might permit additional cognitive resources to be allocated to learning the parameter requirements. However, GMP theory maintains the independence of the memories governing the GMP and parameters. This notion suggests that manipulating the difficulty of the GMP should have no effect on the blocked practice participant's ability to successfully specify the appropriate parameters. Participants learned a simple or complex relative timing pattern under either blocked or random practice conditions. Smaller GMP errors were exhibited for the simple relative timing patterns, but this was not associated with improvements in parameter specification following blocked practice. A clear advantage for parameter specification was evident in transfer following random practice. Taken together, these data support the theoretical separation of the GMP and parameter processes.
Wright and Shea (1991) described intentional stimuli as explicitly identified information necessary to successfully perform a task, whereas incidental stimuli are not explicitly identified as crucial to task performance but have the potential to become associated with particular responses because of their selective presence in the training environment. Shea and Wright (1995), using a speeded-choice RT task, indicated that manipulating the strength of association between incidental information and the responses, by changing the discriminability of incidental stimuli while fixing the strength of the association between the intentional stimuli and each response, had a significant impact on task performance. The present experiment further examined the role played by incidental stimuli when the strength of association between the intentional stimuli and the associated responses was reduced, by minimising stimulus-response compatibility. It was assumed that this latter manipulation would have a similar impact as increasing the strength of incidental stimuli-response relationships. That is, the relative contribution of the incidental stimuli would increase, resulting in an increase in context-dependent behaviour during tests in which the intentional and incidental stimuli activated different responses. The results were in agreement with this prediction and consistent with a model for contextual-dependent performance proposed by Shea and Wright (1995) as well as with the outshining hypothesis forwarded by Smith (1988, 1994).
Telomerase, a ribonucleoprotein, has been described as an essential component of highly proliferative cells as it stabilizes the telomeres and avoids cellular senescence. The objective of this study was to modify the polymerase chain reaction-based telomeric repeat amplification protocol to detect telomerase activity in the single cell and to characterize the activity expressed in the human oocyte through to the blastocyst stage embryo. A comparative evaluation of telomerase activity and developmental stage was conducted using discarded or donated human oocytes and embryos. Telomerase activity was detected in all developmental stages evaluated from immature oocytes through to blastocyst stage embryos. Immature oocytes and blastocysts had similar levels of telomerase activity; however, both groups had significantly (P < 0.05) higher activity than zygote through to pre-morula stage embryos. Seventy-five thawed zygotes were cultured to day 3, biopsied by removing 1-2 cells, and the biopsied embryos were cultured to blastocyst stage. There was no difference (P < 0.05) in telomerase activity between cells biopsied from embryos that reached the blastocyst stage and cells from those that arrested in growth. This study has shown that human oocytes through to blastocyst stage embryos express telomerase activity, but that the level of telomerase activity in biopsied blastomeres, of the day 3 cleavage stage embryo, is not predictive of embryonic growth potential.
[reaction: see text] An approach to the spirocyclic core of halichlorine and pinnaic acid has been designed around an imine allylation/ring-closing metathesis sequence. This sequence has been used to generate several azabicylo[n.5] model systems. A newly reported metathesis catalyst was show to be highly effective for cyclization of these systems.
PURPOSE: To determine whether embryos resulting from oocytes matured in vitro have a higher incidence of nuclear and/or genetic abnormalities compared to embryos resulting from oocytes matured in vivo. METHODS: Fluorescence in situ hybridization analysis for chromosomes X, Y, and 18 was used to compare the rates of aneuploidy, mosaicism, and nuclear abnormalities in embryos derived from oocytes that were prophase I at aspiration (immature group) to that observed in embryos resulting from oocytes that were metaphase I or II at aspiration (mature group). RESULTS: Based on nuclear morphology, significantly more embryos in the mature group (23%) were classified as normal compared to embryos in the immature group (3%). No difference was found in the rate of aneuploidy or in the incidence of mosaicism involving these chromosomes. CONCLUSIONS: These findings suggest that few embryos derived from prophase I oocytes collected following ovarian stimulation are morphologically normal.
In 2 experiments, the authors studied the effectiveness of physical and observational practice on learning and the effect on learning of combining physical practice and observation, as compared with providing physical practice alone. In Experiment 1, retention and transfer performance of 30 university students after physical, observational, or no practice were contrasted. Consistent with findings from other studies, the retention results indicated that observational practice is inferior to physical practice. The transfer data indicated no differences between observation and physical practice groups. In Experiment 2, retention and transfer performance of 30 participants in physical and combined (alternating physical and observational) practice groups were contrasted. The retention results showed no differences between the combined and physical practice groups, but the combined group performed significantly better than the physical practice group on the transfer test. Those findings suggest that a combination of observation and physical practice permits unique opportunities for learning beyond those available via either practice regimen alone.
In 2 experiments, the authors manipulated the frequency of concurrent feedback to discern the effects on learning. In each experiment, participants (N = 48, Experiment 1; N = 36, Experiment 2) attempted to reproduce a criterion force-production waveform (5 s in duration) presented on the computer monitor. Consistent with the guidance hypothesis, the results of Experiment 1 indicated very strong guiding effects of concurrent feedback and strong dependence on the feedback, as indicated by participants' extremely poor performance upon feedback withdrawal in retention. As predicted by the guidance hypothesis, dependence on the feedback was reduced as a result of reducing the frequency of the concurrent feedback. The results of Experiment 2 indicated that one can enhance learning by providing concurrent and terminal feedback on 1 trial, with no feedback on the subsequent trial. In that way, the strong guiding effects of concurrent feedback could be realized and the beneficial effects of terminal feedback could also be achieved.
Two experiments examined generalized motor program (GMP) and parameter learning. Experiment 1 examined the effects of bandwidth knowledge of results (KR) about relative timing in constant and variable practice. The purpose was to determine if movement stability created by the bandwidth manipulation is associated with increased GMP learning and if bandwidth KR interacts with constant and variable practice. Participants were asked to depress four keys sequentially, using the same relative timing structure. Constant practice had one absolute timing requirement, whereas variable practice had three different absolute timing requirements. The results indicated that GMP learning was enhanced by constant practice (independent of the bandwidth KR condition) and by bandwidth KR, when variable practice was used. The findings suggest practice conditions (bandwidth KR, constant practice) that increase movement stability during practice enhance GMP learning. Parameter learning (during transfer), however, was enhanced by variable practice. Experiment 2 attempted to determine how constant and variable practice conditions could be combined to enhance both GMP and parameter learning. The results indicated that developing a stable GMP early in practice--by providing learners with constant practice early in practice--and refining parameter learning later in practice--by providing them with variable practice late in practice--were effective for both GMP and parameter learning. This suggests a hierarchy in the development of programmed actions with a stable GMP being a requisite for developing an effective and stable parameter rule.
Two experiments are reported that examined the usefulness of observational learning for acquiring both error detection and movement production capabilities. In both experiments, individuals were assigned to a no-practice, physical-practice, or observational practice condition. Those assigned to a physical-practice condition acted as models for those assigned as observers. In both experiments, models were administered a random practice of three serial key-press tasks that had the same spatial pattern and same relative timing requirement but differed in the overall time goal. During the retention test, individuals provided estimates of their overall time after each trial. Data from these experiments revealed that error detection and overall time specification were similar following observation and physical practice. However, data from Experiment 2 indicated that physical practice offered an advantage beyond that afforded via observation, with regard to acquiring the appropriate relative time pattern. These data are discussed with respect to the role of observation for learning movement recognition and production processes.
The reported study used the dual-task methodology to assess the attention demands associated with high and low contextual interference (CI) practice environments. Two specific issues were addressed. First, is there a difference in the attention demands during random and blocked schedules of practice? Second, what is the time course of any differential attention demands that emerge during random and blocked training? In order to address these questions two specific temporal loci were probed during practice: a pre-response interval and the inter-trial interval. It was assumed that the pre-response interval contained the reconstructive activity that is central to the reconstruction position. In contrast, the inter-trial interval has been interpreted in previous work to be the interval in which critical intra- and inter-item processing is performed during random practice. The data revealed a typical CI effect for the primary key-pressing task. Specifically, blocked-practice participants displayed superior performance during training but performed less well than the random-practice individuals at the time of retention. The poorer acquisition performance of the random-practice participants was associated with higher cognitive demand during both the pre-response and the inter-trial intervals than that of individuals assigned to blocked practice. The greater attention demands for random-practice individuals are discussed with respect to processes that might occur in both the pre-response and the inter-trial intervals.
[formula: see text] Compounds that induce the synthesis of nerve growth factor (NGF) are of interest as alternatives to the administration of the native peptide. We have initiated a program to study the NGF synthesis stimulating activity of the erinacine and scabronine diterpenes. Herein, we report an approach to the core cyathin system by sequential application of an oxidative coupling and [4 + 3] cycloaddition.
A system for automatic modeling of anatomical joint motion for use in the Virtual Reality Dynamic Anatomic (VRDA) tool is described. The modeling method described in this article relies on collision detection. An original incremental algorithm use this information to achieve stable positions and orientations of the tibia on the femur for each angle considered between these two components on the range of motion. The stable states then become the basis for a look-up table employed in the animation of the motion of the joint. The strength of the method lies in its robustness to animate any "normal" anatomical joint, given a set of kinematic constraints for the joint type as well as an accurate 3D geometric model of the joint. The demonstration could be patient specific (based on a person's real anatomical data from an imaging procedure such as CT scanning) or scaled from a generic joint based on external patient measurements. The modeling method has been implemented on a generic knee model for use in the VRDA tool.
The present experiment was designed to address the role of task difficulty for the development of contextual-dependent behaviour during perceptual-motor task acquisition. Task difficulty in the present study was manipulated by restricting the time that the subject; (a) viewed task-relevant information, and (b) was afforded to execute a sequence of key presses. Assuming these manipulations made the acquisition of the key press tasks more difficult, it was hypothesised that reducing the time for either of these processes would result in a greater dependence on reinstating the training context at the time of test. This was based on previous findings reported by Wright and Shea (1991) which indicated that task difficulty can contribute to the development of context-dependent behaviour. The results of the study revealed that viewing time was a potent difficulty manipulation. This is supported by the slower acquisition rates for subjects exposed to short as opposed to long viewing conditions during training. More importantly, the impact of changing the intentional-incidental stimuli relationship that was apparent during training, during the test was greatest for the individuals who experienced shorter viewing times during the training phase. Thus, the proposed influence of task difficulty on contextual-dependent performance was supported. This dependency was manifested as a slowing in both the initiation and execution of the correct key presses. It is proposed that individuals trained in the more difficult viewing condition during training, when faced with an incongruence in the acquisition and test stimuli, must engage additional data-driven verification processes to supplement their extant knowledge in order to execute an appropriate response.