Simulation-based conjoint ranking for optimal decision support process under aleatory uncertainty

Design chain management requires many decision makers throughout the product development process. It is critical to reduce complexity and uncertainty of the design process by correctly modeling subjective data associated with decision makers’ preferences. This paper aims at using decision support to find optimal designs by modeling respondent preferences and trade-offs with consideration of uncertainty. Specifically, a simulation-based ranking methodology is implemented and incorporated with traditional conjoint analysis. This process facilitates a schematic decision support process by alleviating user fatigue. In addition, incorporation of uncertainty in the ranking process provides the capability of producing robust and reliable products. The efficacy and applicability of simulation-based conjoint ranking is demonstrated with a case study of a power-generating shock absorber design.     

Combination of systemic acetazolamide and topical dorzolamide in reducing intraocular pressure and aqueous humor formation

BACKGROUND: Neuroendocrine tumors commonly metastasize to the liver. Although surgical resection is considered a treatment option for patients with localized metastases confined to the liver, the longterm survival benefit of liver resection has not been clearly demonstrated. We examined the survival of patients undergoing liver resection for this disease. STUDY DESIGN: Between 1984 and 1995, we evaluated 38 patients with liver-only metastases from neuroendocrine tumors, including 21 carcinoid, 13 islet cell, and 4 atypical neuroendocrine neoplasms. Data from a combined prospective and retrospective database and a tumor registry were analyzed. Of these patients, 15 underwent complete resection of all known disease. The remaining 23 patients, who also had disease confined to the liver, had comparable tumor burden but were believed to be unresectable. The longterm survival rates of these two groups were compared. RESULTS: Patients who underwent liver resection did not differ from those who were unresectable with regard to age, pathology, primary tumor site, serum alkaline phosphatase levels, or percentage of the liver involved. All resections were complete, leaving no residual disease, and consisted of lobectomy (n = 3), segmentectomy (n = 1), and wedge resections (n = 11). There were no operative deaths. Patients who underwent hepatic resection had a significantly longer survival than unresected patients. Although median survival had not been reached in resected patients, the median survival in the unresectable group was 27 months. Patients who underwent liver resection had a higher 5-year actuarial survival (73% versus 29%). CONCLUSIONS: Hepatic resection in selected patients with isolated liver metastases from neuroendocrine tumors may prolong survival. This conclusion was reached by comparing our resected group with an unresectable group with similar tumor burden.     

The cyclin-dependent kinase inhibitor p27(Kip1) induces N-terminal proteolytic cleavage of cyclin A

Progression through the cell cycle is regulated in part by the sequential activation and inactivation of cyclin-dependent kinases (CDKs). Many signals arrest the cell cycle through inhibition of CDKs by CDK inhibitors (CKIs). p27(Kip1) (p27) was first identified as a CKI that binds and inhibits cyclin A/CDK2 and cyclin E/CDK2 complexes in G1. Here we report that p27 has an additional property, the ability to induce a proteolytic activity that cleaves cyclin A, yielding a truncated cyclin A lacking the mitotic destruction box. Other CKIs (p15(Ink4b), p16(Ink4a), p21(Cip1), and p57(Kip2)) do not induce cleavage of cyclin A; other cyclins (cyclin B, D1, and E) are not cleaved by the p27-induced protease activity. The C-terminal half of p27, which is dispensable for its kinase inhibitory activity, is required to induce cleavage. Mechanistically, p27 does not appear to cause cleavage through direct interaction with cyclin/CDK complexes. Instead, it activates a latent protease that, once activated, does not require the continuing presence of p27. Mutation of cyclin A at R70 or R71, residues at or very close to the cleavage site, blocks cleavage. Noncleavable mutants are still recognized by the anaphase-promoting complex/cyclosome pathway responsible for ubiquitin-dependent proteolysis of mitotic cyclins, indicating that the p27-induced cleavage of cyclin A is part of a separate pathway. We refer to this protease as Tsap (pTwenty-seven- activated protease).     

Independent component analysis of natural image sequences yields spatio-temporal filters similar to simple cells in primary visual cortex

Simple cells in the primary visual cortex process incoming visual information with receptive fields localized in space and time, bandpass in spatial and temporal frequency, tuned in orientation, and commonly selective for the direction of movement. It is shown that performing independent component analysis (ICA) on video sequences of natural scenes produces results with qualitatively similar spatio-temporal properties. Whereas the independent components of video resemble moving edges or bars, the independent component filters, i.e. the analogues of receptive fields, resemble moving sinusoids windowed by steady Gaussian envelopes. Contrary to earlier ICA results on static images, which gave only filters at the finest possible spatial scale, the spatio-temporal analysis yields filters at a range of spatial and temporal scales. Filters centred at low spatial frequencies are generally tuned to faster movement than those at high spatial frequencies.     

Insulin-stimulated phosphatidylinositol 3-kinase. Association with a 185-kDa tyrosine-phosphorylated protein (IRS-1) and localization in a low density membrane vesicle

Insulin stimulates the appearance of anti-tyrosine(P)-immunoprecipitable phosphatidylinositol 3-kinase (PI 3-kinase) activity in adipocytes, predominantly in an intracellular membrane fraction (Kelly, K. L., Ruderman, N. B., and Chen, K. S. (1992) J. Biol. Chem. 267, 3423-3428). Neither the mechanism underlying this activation nor the precise subcellular compartment in which it occurs is known. To address these questions, studies were performed using isolated rat adipocytes and subcellular fractions of these cells. In intact cells, insulin stimulated the rapid appearance of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate in 32P-labeled adipocytes without changing the labeling of phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, or phosphatidylinositol 4,5-bisphosphate. This effect was accompanied by the tyrosyl phosphorylation of a 185-kDa protein, tentatively identified as IRS-1, with which PI 3-kinase became associated. The majority of the p85, the regulatory subunit of PI 3-kinase, in untreated adipocytes was present in the cytosol; however, neither the activity of PI 3-kinase nor the total amount of p85 in this fraction was modified in response to insulin. In contrast, insulin increased the association of p85 with IRS-1, the tyrosyl phosphorylation of the IRS-1 associated with p85, and the total activity of PI 3-kinase in the plasma membranes and low density membranes. After insulin treatment, similar amounts of p85 were bound to IRS-1 in the low density and plasma membrane fractions; however, tyrosyl-phosphorylated IRS-1 and PI 3-kinase activity were an order of magnitude greater in the low density membranes. The complex of tyrosyl-phosphorylated IRS-1.p85 that formed in response to insulin was localized to a very low density vesicle subpopulation that could be distinguished from vesicles containing the GLUT-4 glucose transporter and the insulin receptor. These data suggest that the activation of PI 3-kinase by insulin in the adipocyte involves the formation of a complex between IRS-1 and PI 3-kinase in a very low density membrane fraction that is not enriched in GLUT-4 or insulin receptors. They also suggest that PI 3-kinase activation correlates more closely with the extent of tyrosyl phosphorylation of the IRS-1 complexed to PI 3-kinase than it does to the amount of p85 bound to IRS-1.     

Modeling and Identification of Elastic Robot Joints With Hysteresis and Backlash

This paper presents a novel approach to the modeling and identification of elastic robot joints with hysteresis and backlash. The model captures the dynamic behavior of a rigid robotic manipulator with elastic joints. The model includes electromechanical submodels of the motor and gear from which the relationship between the applied torque and the joint torsion is identified. The friction behavior in both presliding and sliding regimes is captured by generalized Maxwell-slip model. The hysteresis is described by a Preisach operator. The distributed model parameters are identified from experimental data obtained from internal system signals and external angular encoder mounted to the second joint of a 6-DOF industrial robot. The validity of the identified model is confirmed by the agreement of its prediction with independent experimental data not previously used for model identification. The obtained models open an avenue for future advanced high-precision control of robotic manipulator dynamics.     

Monte Carlo model of the penetration depth for polarization gating spectroscopy: influence of illumination-collection geometry and sample optical properties

Polarization-gating has been widely used to probe superficial tissue structures, but the penetration depth properties of this method have not been completely elucidated. This study employs a polarization-sensitive Monte Carlo method to characterize the penetration depth statistics of polarization-gating. The analysis demonstrates that the penetration depth depends on both the illumination-collection geometry [illumination-collection area (R) and collection angle (θ(c))] and on the optical properties of the sample, which include the scattering coefficient (μ(s)), absorption coefficient (μ(a)), anisotropy factor (g), and the type of the phase function. We develop a mathematical expression relating the average penetration depth to the illumination-collection beam properties and optical properties of the medium. Finally, we quantify the sensitivity of the average penetration depth to changes in optical properties for different geometries of illumination and collection. The penetration depth model derived in this study can be applied to optimizing application-specific fiber-optic probes to target a sampling depth of interest with minimal sensitivity to the optical properties of the sample.     

Detector Development for the Next Phases of the Cryogenic Dark Matter Search: Results from 1 Inch Ge and Si Detectors

The Cryogenic Dark Matter Search (CDMS) experiment is searching for Weakly Interacting Massive Particles (WIMPs) using detectors with the ability to discriminate between candidate (nuclear recoil) and background (electron recoil) events by measuring both phonon and ionization signals from recoils in the detector crystals. As CDMS scales up to greater WIMP sensitivity, it is necessary to increase the detector mass and further improve background discrimination. CDMS is engaged in ongoing fabrication and development of new detector designs in order to meet these criteria for the proposed SuperCDMS experiment. Thicker detector prototypes have been produced with new photolithographic masks. These masks have greater surface coverage of the quasi particle trap and transition edge sensor system to provide superior athermal phonon collection. Results from continuing laboratory tests are presented which already indicate improvement in discrimination parameters.      

Dysphoric mood and overeating: A test of restraint theory's disinhibition hypothesis.

Tested the hypothesis that restrained eaters overindulge when experiencing emotional arousal. A dysphoric or nondysphoric mood was induced in 104 normal-weight female college students who had completed the Restraint Scale. Ss completed a bogus "culture-free intelligence test" that consisted of either unsolvable problems (dysphoric mood condition) or solvable problems (nondysphoric mood condition). Mood was measured by the Multiple Affect Adjective Check List. After the mood induction, Ss' cracker consumption was measured in a taste test. Consistent with restraint theory's prediction, the results revealed a significant Restraint by Mood interaction, with restrained eaters eating more when in a dysphoric than in a nondysphoric mood, and unrestrained eaters consuming similar amounts in both mood states. The predictive powers of 2 subscales of the Restraint Scale, Weight Fluctuation (WF) and Concern with Dieting (CD), were also compared. CD scores were better predictors of the amount eaten by Ss in a dysphoric mood than were WF or total restraint scores. This suggests that the 2 subscales of the Restraint Scale are worth distinguishing and that the CD scale may be the more valid of the 2 scales. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)