NMDA-based pattern discrimination in a modeled cortical neuron

Compartmental simulations of an anatomically characterized cortical pyramidal cell were carried out to study the integrative behavior of a complex dendritic tree. Previous theoretical (Feldman and Ballard 1982; Durbin and Rumelhart 1989; Mel 1990; Mel and Koch 1990; Poggio and Girosi 1990) and compartmental modeling (Koch et al. 1983; Shepherd et al. 1985; Koch and Poggio 1987; Rall and Segev 1987; Shepherd and Brayton 1987; Shepherd et al. 1989; Brown et al. 1991) work had suggested that multiplicative interactions among groups of neighboring synapses could greatly enhance the processing power of a neuron relative to a unit with only a single global firing threshold. This issue was investigated here, with a particular focus on the role of voltage-dependent N-methyl-D-asparate (NMDA) channels in the generation of cell responses. First, it was found that when a large proportion of the excitatory synaptic input to dendritic spines is carried by NMDA channels, the pyramidal cell responds preferentially to spatially clustered, rather than random, distributions of activated synapses. Second, based on this mechanism, the NMDA-rich neuron is shown to be capable of solving a nonlinear pattern discrimination task. We propose that manipulation of the spatial ordering of afferent synaptic connections onto the dendritic arbor is a possible biological strategy for pattern information storage during learning

Induction plasma calcining of pigment particles for thermal control coatings Final report, 9 Feb. - 8 Aug. 1968

Induction plasma heating techniques used to calcinate pigment particles for thermal control coating

Study of Growth Parameters for Refractory Carbide Single Crystals Quarterly Status Report No. 9, 1 Mar. - 1 Jun. 1966

Growth parameters for refractory carbide single crystal

Pressure and heat-transfer distributions in a simulated wing-elevon cove with variable leakage at a free-stream Mach number of 6.9

An experimental aerodynamic heating investigation was conducted to determine effects of hot boundary-layer ingestion into the cove on the windward surface between a wing and elevon for cove seal leak areas nominally between 0 and 100 percent of cove entrance area. Pressure and heating-rate distributions were obtained on the wing and elevon surfaces and on the cove walls of a full-scale model that represented a section of the cove region on the space shuttle orbiter. Data were obtained for both attached and separated turbulent boundary layers upstream of the unswept cove entrance. Average free-stream Mach number was 6.9, average free-stream unit Reynolds numbers were 1.31 x 10 to the 6th power and 4.40 x 10 to the 6th power per meter (0.40 x 10 to the 6th power and 1.34 x 10 to the 6th power per foot), and average total temperature was 1888 K (3400 R). Cove pressures and heating rates varied as a function of seal leak area independent of leak aspect ratio. Although cove heating rates for attached flow did not appear intolerable, it was postulated that convective heating in the cove may increase with time. For separated flow, the cove environment was considered too severe for unprotected interior structures of control surfaces

Study of growth parameters for refractory carbide single crystals Quarterly status report no. VIII, 1 Dec. 1965 - 1 Mar. 1966

Growth parameters for refractory carbide single crystal

Study of growth parameters for refractory carbide single crystals Quarterly status report no. 7, Sep. 1 - Dec. 1, 1965

Crystal growth experiments to explore influence of atmospheric compositions, during melting, on crystal stochiometry emphasizing determination of tantalum solubilit

Bayesian correction for covariate measurement error: a frequentist evaluation and comparison with regression calibration

Bayesian approaches for handling covariate measurement error are well established, and yet arguably are still relatively little used by researchers. For some this is likely due to unfamiliarity or disagreement with the Bayesian inferential paradigm. For others a contributory factor is the inability of standard statistical packages to perform such Bayesian analyses. In this paper we first give an overview of the Bayesian approach to handling covariate measurement error, and contrast it with regression calibration (RC), arguably the most commonly adopted approach. We then argue why the Bayesian approach has a number of statistical advantages compared to RC, and demonstrate that implementing the Bayesian approach is usually quite feasible for the analyst. Next we describe the closely related maximum likelihood and multiple imputation approaches, and explain why we believe the Bayesian approach to generally be preferable. We then empirically compare the frequentist properties of RC and the Bayesian approach through simulation studies. The flexibility of the Bayesian approach to handle both measurement error and missing data is then illustrated through an analysis of data from the Third National Health and Nutrition Examination Survey

Insights into the kinetics of siRNA-mediated gene silencing from live-cell and live-animal bioluminescent imaging

Small interfering RNA (siRNA) molecules are potent effectors of post-transcriptional gene silencing. Using noninvasive bioluminescent imaging and a mathematical model of siRNA delivery and function, the effects of target-specific and treatment-specific parameters on siRNA-mediated gene silencing are monitored in cells stably expressing the firefly luciferase protein. In vitro, luciferase protein levels recover to pre-treatment values within <1 week in rapidly dividing cell lines, but take longer than 3 weeks to return to steady-state levels in nondividing fibroblasts. Similar results are observed in vivo, with knockdown lasting ~10 days in subcutaneous tumors in A/J mice and 3–4 weeks in the nondividing hepatocytes of BALB/c mice. These data indicate that dilution due to cell division, and not intracellular siRNA half-life, governs the duration of gene silencing under these conditions. To demonstrate the practical use of the model in treatment design, model calculations are used to predict the dosing schedule required to maintain persistent silencing of target proteins with different half-lives in rapidly dividing or nondividing cells. The approach of bioluminescent imaging combined with mathematical modeling provides useful insights into siRNA function and may help expedite the translation of siRNA into clinically relevant therapeutics for disease treatment and management