Amniotic fluid brain-specific proteins are biomarkers for spinal cord injury in experimental myelomeningocele

Myelomeningocele (MMC), the most severe form of spina bifida (SB), causes neurological deficit. Injury to the spinal cord is thought to begin in utero. We investigated whether brain-specific proteins (BSPs) would enable us to monitor the development of MMC-related tissue damage during pregnancy in an animal model with naturally occurring SB (curly tail/loop tail mouse; n = 256). Amniotic fluid levels of neurofilament heavy chain (NfH), glial acidic fibrillary protein (GFAP) and S100B were measured by standard ELISA techniques. The amniotic fluid levels of all BSPs were similar in SB and control mice on embryonic day (E) 12.5 and 14.5, whereas a significant increase was observed for GFAP in SB mice on E16.5. Levels of all BSPs were significantly increased in SB mice on E18.5. The rapid increase in GFAP, paralleled by a moderate increase in NfH and S100B, suggests that spinal cord damage starts to accelerate around E16.5. The macroscopic size of the MMC was related to NfH level on E16.5 and E18.5, suggesting that axonal degeneration is most severe in large MMC. Amniotic fluid BSP measurements may provide important information for balancing the risks and benefits to mother and child of in utero surgery for MMC

Analysis and simulations of multifrequency induction hardening

We study a model for induction hardening of steel. The related differential system consists of a time domain vector potential formulation of the Maxwell's equations coupled with an internal energy balance and an ODE for the volume fraction of {\sl austenite}, the high temperature phase in steel. We first solve the initial boundary value problem associated by means of a Schauder fixed point argument coupled with suitable a-priori estimates and regularity results. Moreover, we prove a stability estimate entailing, in particular, uniqueness of solutions for our Cauchy problem. We conclude with some finite element simulations for the coupled system

Quantification of neurodegeneration by measurement of brain-specific proteins

Quantification of neurodegeneration in animal models is typically assessed by time-consuming and observer-dependent immunocytochemistry. This study aimed to investigate if newly developed ELISA techniques could provide an observer-independent, cost-effective and time-saving tool for this purpose. Neurofilament heavy chain (NfH(SM135)), astrocytic glial fibrillary acidic protein (GFAP), S100B and ferritin, markers of axonal loss, gliosis, astrocyte activation and microglial activation, respectively, were quantified in the spinal cord homogenates of mice with chronic relapsing experimental allergic encephalomyelitis (CREAE, n=8) and controls (n=7). Levels of GFAP were found to be threefold elevated in CREAE (13 ng/mg protein) when compared to control animals (4.5 ng/mg protein, p<0.001). The inverse was observed for NfH(SM135) (21 ng/mg protein vs. 63 ng/mg protein, p<0.001), ferritin (542 ng/mg protein vs. 858 ng/mg protein, p<0.001) and S100B (786 ng/mg protein vs. 2080 ng/mg protein, N.S.). These findings were confirmed by immunocytochemistry, which demonstrated intense staining for GFAP and decreased staining for NfH(SM135) in CREAE compared to control animals. These findings indicate that axonal loss and gliosis can be estimated biochemically using the newly developed ELISA assays for NfH(SM135) and GFAP. These assays may facilitate the quantification of pathological features involved in neurodegeneration

Hyperextended Scalar-Tensor Gravity

We study a general Scalar-Tensor Theory with an arbitrary coupling funtion $\omega (\phi )$ but also an arbitrary dependence of the ``gravitational constant'' $G(\phi )$ in the cases in which either one of them, or both, do not admit an analytical inverse, as in the hyperextended inflationary scenario. We present the full set of field equations and study their cosmological behavior. We show that different scalar-tensor theories can be grouped in classes with the same solution for the scalar field.Comment: latex file, To appear in Physical Review

Treatment response in relation to inflammatory and axonal surrogate marker in multiple sclerosis

BACKGROUND: This study aimed to investigate if treatment response could retrospectively be related to inflammatory or axonal pathology as measured by plasma surrogate markers. METHODS: In this 1-year observational study 30 multiple sclerosis (MS) patients with relapsing-remitting disease were treated with intramuscular IFNbeta-1a or subcutaneous IFNbeta-1b. Responders and nonresponders were defined according to clinical and magnetic resonance imaging criteria. The control group consisted of 14 healthy subjects. Plasma levels of surrogate markers for inflammation (nitric oxide metabolites (NOx)), astrocytic activation (S100B) and axonal damage (NfH(SM135)) were measured using standard assays. RESULTS: There were 11 nonresponders and 19 responders to IFNbeta treatment. Median S100B levels were elevated in a higher proportion of treatment responders (63%, 42.9 pg/mL) compared to nonresponders (18%, 11.7 pg/mL, P < 0.05, Fisher's exact test) and controls (0%, 2 pg/mL, P < 0.001). Levels of NOx were found to be more frequently elevated in nonresponders (72%, 39 microM) compared to healthy controls (0%, 37 microM, P < 0.05). Levels of NfH(SM135) were more frequently elevated in responders (58%, 300 pg/mL, P < 0.001) and nonresponders (72%, 500 pg/mL, P < 0.001) compared to controls (0%, 4.5 pg/mL). CONCLUSION: Patients with relapsing-remitting MS who had surrogate marker supported evidence for astrocytic activation responded more frequently to treatment with IFNbeta

Some exact non-vacuum Bianchi VI0 and VII0 instantons

We report some new exact instantons in general relativity. These solutions are K\"ahler and fall into the symmetry classes of Bianchi types VI0 and VII0, with matter content of a stiff fluid. The qualitative behaviour of the solutions is presented, and we compare it to the known results of the corresponding self-dual Bianchi solutions. We also give axisymmetric Bianchi VII0 solutions with an electromagnetic field.Comment: latex, 15 pages with 3 eps figure

Sequence effects in the categorization of tones varying in frequency

In contrast to exemplar and decision-bound categorization models, the memory and contrast models described here do not assume that long-term representations of stimulus magnitudes are available. Instead, stimuli are assumed to be categorized using only their differences from a few recent stimuli. To test this alternative, the authors examined sequential effects in a binary categorization of 10 tones varying in frequency. Stimuli up to 2 trials back in the sequence had a significant effect on the response to the current stimulus. The effects of previous stimuli interacted with one another. A memory and contrast model, according to which only ordinal information about the differences between the current stimulus and recent preceding stimuli is used, best accounted for these dat

Optimal control for halo orbit missions

This paper addresses the computation of the required trajectory correction maneuvers (TCM) for a halo orbit space mission to compensate for the launch velocity errors introduced by inaccuracies of the launch vehicle. By combiningdynamical systems theory with optimal control techniques, we produce a portrait of the complex landscape of the trajectory design space. This approach enables parametric studies not available to mission designers a few years ago, such as how the magnitude of the errors and the timingof the first TCM affect the correction ΔV. The impetus for combiningdynamical systems theory and optimal control in this problem arises from design issues for the Genesis Discovery mission being developed for NASA by the Jet Propulsion Laboratory