The development of computational techniques for the identification of linear and nonlinear mechanical systems subject to random excitation, part 2 Final report

Computational techniques for identifying linear and nonlinear mechanical systems subject to random excitatio

Identification of linear systems. Simulation studies Final report, Feb. 1967 - Apr. 1968

Analytical development and computerized simulation of parameter estimation technique for identifying linear and nonlinear system

Computerized Adaptive Tests Detect Change Following Orthopaedic Surgery in Youth with Cerebral Palsy.

BACKGROUND: The Cerebral Palsy Computerized Adaptive Test (CP-CAT) is a parent-reported outcomes instrument for measuring lower and upper-extremity function, activity, and global health across impairment levels and a broad age range of children with cerebral palsy (CP). This study was performed to examine whether the Lower Extremity/Mobility (LE) CP-CAT detects change in mobility following orthopaedic surgery in children with CP. METHODS: This multicenter, longitudinal study involved administration of the LE CP-CAT, the Pediatric Outcomes Data Collection Instrument (PODCI) Transfer/Mobility and Sports/Physical Functioning domains, and the Timed Up & Go test (TUG) before and after elective orthopaedic surgery in a convenience sample of 255 children, four to twenty years of age, who had CP and a Gross Motor Function Classification System (GMFCS) level of I, II, or III. Standardized response means (SRMs) and 95% confidence intervals (CIs) were calculated for all measures at six, twelve, and twenty-four months following surgery. RESULTS: SRM estimates for the LE CP-CAT were significantly greater than the SRM estimates for the PODCI Transfer/Mobility domain at twelve months, the PODCI Sports/Physical Functioning domain at twelve months, and the TUG at twelve and twenty-four months. When the results for the children at GMFCS levels I, II, and III were grouped together, the improvements in function detected by the LE CP-CAT at twelve and twenty-four months were found to be greater than the changes detected by the PODCI Transfer/Mobility and Sports/Physical Functioning scales. The LE CP-CAT outperformed the PODCI scales for GMFCS levels I and III at both of these follow-up intervals; none of the scales performed well for patients with GMFCS level II. CONCLUSIONS: The results of this study showed that the LE CP-CAT displayed superior sensitivity to change than the PODCI and TUG scales after musculoskeletal surgery in children with CP

Integrity of H1 helix in prion protein revealed by molecular dynamic simulations to be especially vulnerable to changes in the relative orientation of H1 and its S1 flank

In the template-assistance model, normal prion protein (PrPC), the pathogenic cause of prion diseases such as Creutzfeldt-Jakob (CJD) in human, Bovine Spongiform Encephalopathy (BSE) in cow, and scrapie in sheep, converts to infectious prion (PrPSc) through an autocatalytic process triggered by a transient interaction between PrPC and PrPSc. Conventional studies suggest the S1-H1-S2 region in PrPC to be the template of S1-S2 $\beta$-sheet in PrPSc, and the conformational conversion of PrPC into PrPSc may involve an unfolding of H1 in PrPC and its refolding into the $\beta$-sheet in PrPSc. Here we conduct a series of simulation experiments to test the idea of transient interaction of the template-assistance model. We find that the integrity of H1 in PrPC is vulnerable to a transient interaction that alters the native dihedral angles at residue Asn$^{143}$, which connects the S1 flank to H1, but not to interactions that alter the internal structure of the S1 flank, nor to those that alter the relative orientation between H1 and the S2 flank.Comment: A major revision on statistical analysis method has been made. The paper now has 23 pages, 11 figures. This work was presented at 2006 APS March meeting session K29.0004 at Baltimore, MD, USA 3/13-17, 2006. This paper has been accepted for pubcliation in European Biophysical Journal on Feb 2, 200

Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice.

BackgroundSpinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia.MethodsL5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in male Tlr2-/-Tlr3-/-, Tlr4-/-, Tlr5-/-, Myd88-/-, Triflps2, Myd88/Triflps2, Tnf-/-, and Ifnar1-/- mice. We also examined L5 ligation in Tlr4-/- female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferroni post hoc test was used.ResultsIn WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in female Tlr4-/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNβ, released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia.ConclusionsThese observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice

Effect-Directed Analysis of Municipal Landfill Soil Reveals Novel Developmental Toxicants in the Zebrafish Danio rerio

Effect-directed analysis (EDA) is an approach used to identify (unknown) contaminants in complex samples which cause toxicity, using a combination of biology and chemistry. The goal of this work was to apply EDA to identify developmental toxicants in soil samples collected from a former municipal landfill site. Soil samples were extracted, fractionated, and tested for developmental effects with an embryotoxicity assay in the zebrafish Danio rerio. Gas chromatograph mass selective detection (GC-MSD) chemical screening was used to reveal candidate developmental toxicants in fractions showing effects. In a parallel study, liquid chromatography-hybrid linear ion trap Orbitrap mass spectrometry was also applied to one polar subfraction (Hoogenboom et al. J. Chromatogr. A2009, 1216, 510-519). EDA resulted in the identification of a number of previously unknown developmental toxicants, which were confirmed to be present in soil by GC-MS. These included 11H-benzo[b]fluorene, 9-methylacridine, 4-azapyrene, and 2-phenylquinoline, as well as one known developmental toxicant (retene). This work revealed the presence of novel contaminants in the environment that may affect vertebrate development, which are not subject to monitoring or regulation under current soil quality assessment guidelines. © 2011 American Chemical Society

Synthesis of accelerograms compatible with the Chinese GB 50011-2001 design spectrum via harmonic wavelets: artificial and historic records

A versatile approach is employed to generate artificial accelerograms which satisfy the compatibility criteria prescribed by the Chinese aseismic code provisions GB 50011-2001. In particular, a frequency dependent peak factor derived by means of appropriate Monte Carlo analyses is introduced to relate the GB 50011-2001 design spectrum to a parametrically defined evolutionary power spectrum (EPS). Special attention is given to the definition of the frequency content of the EPS in order to accommodate the mathematical form of the aforementioned design spectrum. Further, a one-to-one relationship is established between the parameter controlling the time-varying intensity of the EPS and the effective strong ground motion duration. Subsequently, an efficient auto-regressive moving-average (ARMA) filtering technique is utilized to generate ensembles of non-stationary artificial accelerograms whose average response spectrum is in a close agreement with the considered design spectrum. Furthermore, a harmonic wavelet based iterative scheme is adopted to modify these artificial signals so that a close matching of the signals’ response spectra with the GB 50011-2001 design spectrum is achieved on an individual basis. This is also done for field recorded accelerograms pertaining to the May, 2008 Wenchuan seismic event. In the process, zero-phase high-pass filtering is performed to accomplish proper baseline correction of the acquired spectrum compatible artificial and field accelerograms. Numerical results are given in a tabulated format to expedite their use in practice

Structure of the Vesicular Stomatitis Virus N0-P Complex

Replication of non-segmented negative-strand RNA viruses requires the continuous supply of the nucleoprotein (N) in the form of a complex with the phosphoprotein (P). Here, we present the structural characterization of a soluble, heterodimeric complex between a variant of vesicular stomatitis virus N lacking its 21 N-terminal residues (NΔ21) and a peptide of 60 amino acids (P60) encompassing the molecular recognition element (MoRE) of P that binds RNA-free N (N0). The complex crystallized in a decameric circular form, which was solved at 3.0 Å resolution, reveals how the MoRE folds upon binding to N and competes with RNA binding and N polymerization. Small-angle X-ray scattering experiment and NMR spectroscopy on the soluble complex confirms the binding of the MoRE and indicates that its flanking regions remain flexible in the complex. The structure of this complex also suggests a mechanism for the initiation of viral RNA synthesis

Expression of NF-κB p50 in Tumor Stroma Limits the Control of Tumors by Radiation Therapy

Radiation therapy aims to kill cancer cells with a minimum of normal tissue toxicity. Dying cancer cells have been proposed to be a source of tumor antigens and may release endogenous immune adjuvants into the tumor environment. For these reasons, radiation therapy may be an effective modality to initiate new anti-tumor adaptive immune responses that can target residual disease and distant metastases. However, tumors engender an environment dominated by M2 differentiated tumor macrophages that support tumor invasion, metastases and escape from immune control. In this study, we demonstrate that following radiation therapy of tumors in mice, there is an influx of tumor macrophages that ultimately polarize towards immune suppression. We demonstrate using in vitro models that this polarization is mediated by transcriptional regulation by NFκB p50, and that in mice lacking NFκB p50, radiation therapy is more effective. We propose that despite the opportunity for increased antigen-specific adaptive immune responses, the intrinsic processes of repair following radiation therapy may limit the ability to control residual disease