Implicit Motor Learning in Parkinson's Disease.

Objective: This study examined whether disruption of performance is moderated in Parkinson's disease (PD) patients who acquire their motor behaviors in an implicit manner. Method: Twenty-seven patients with PD learned a hammering task in errorless (implicit) or errorful (explicit) conditions and were tested for robustness of motor performance under a secondary task load, which required them to continuously count backward as they performed the hammering task. Results: Patients in the errorless (implicit) motor learning condition exhibited robustness to secondary task loading, whereas patients in the errorful (explicit) motor learning condition did not. Conclusions: Implicit motor learning techniques should be considered by PD rehabilitation specialists in cases in which existing disruption to movements is exacerbated by conscious control. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A phase I-II study of paclitaxel, ifosfamide, and vinorelbine with filgrastim (rhG-CSF) support in advanced non-small-cell lung cancer

PURPOSE: We designed a phase I-II trial of three active agents, paclitaxel, ifosfamide, and vinorelbine, in advanced non-small-cell lung cancer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support; and 2) determine the overall response rate and median survival of patients treated on this regimen. PATIENTS AND METHODS: We treated cohorts of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m2/day x 3 and vinorelbine 20-25 mg/m2/day x 3 and escalating doses of paclitaxel at 100-175 mg/m2 on day 2 with G-CSF support on a 21-day cycle. One prior experimental single-agent chemotherapy regimen was allowed. RESULTS: Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recommended phase II dose (RPTD). Thirteen patients had received prior chemotherapy. Paclitaxel doses of 175 mg/m2 and 150 mg/m2 produced dose-limiting myelosuppression, and the RPTD was determined to be paclitaxel 135 mg/m2 with ifosfamide 1.2 g/m2/day on days 1-3 and vinorelbine 20 mg/m2/ day on days 1-3 with G-CSF support. The overall response rate was 18%, with a median survival of 6.1 months. Six of 35 patients (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia. CONCLUSIONS: This non-cisplatin-containing three-drug regimen has substantial toxicity and low activity in advanced NSCLC, and does not seem to improve on prior regimens. It is unclear whether the lack of efficacy relates to an antagonistic reaction between the specific drugs, administration schedule, or to subtherapeutic doses of the individual agents.     

Models for the elastic deformation of honeycombs

A theoretical model has been developed for predicting the elastic constants of honeycombs based on the deformation of the honeycomb cells by flexure, stretching and hinging. This is an extension of earlier work based on flexure alone. The model has been used to derive expressions for the tensile moduli, shear moduli and Poisson's ratios. Examples are given of structures with a negative Poisson's ratio. It is shown how the properties can be tailored by varying the relative magnitudes of the force constants for the different deformation mechanisms. Off-axis elastic constants are also calculated and it is shown how the moduli and Poisson's ratios vary with applied loading direction. Depending on the geometry of the honeycomb the properties may be isotropie (for regular hexagons) or extremely anisotropic. Again, the degree of anisotropy is also affected by the relative magnitude of the force constants for the three deformation mechanisms.     

A device to measure the cross-sectional area of soft connectivetissues

A device has been designed and fabricated to measure the cross-sectional area of soft connective tissues ex vivo. It consists of two displacement transducers; one sensing tissue thickness and the other sensing width. Outputs are recorded (via an analog to digital interface) using a personal computer. Numerical integration of a thickness versus width plot computes cross-sectional area. This plot also provides a quality check of acquired data. This device has been successfully used in biomechanical studies of rabbit patellar tendons, rat medial collateral ligaments, and dissected specimens of human fascia.     

Enhancement by SO2 of initial activity for selective catalytic reduction of NO with CH3OH over \gamma-alumina

The effect of SO₂ on catalytic activity for NO reduction to N₂ by methanol in excess oxygen over $\gamma$ -alumina has been investigated. SCR activity increased initially upon exposure of a fresh $\gamma$ -alumina catalyst to SO₂ which is attributed to formation of Brønsted acid sites. Longer exposure to SO₂ leads to a decline in catalytic activity to a lower steady-state NO_x reduction activity which is independent of the SO₂ content in the feed gas.     

L-thiocitrulline. A stereospecific, heme-binding inhibitor of nitric-oxide synthases

Nitric-oxide synthase (NOS) catalyzes the oxidation of L-arginine to citrulline and nitric oxide (NO). The enzyme is inhibited by a variety of N omega-monosubstituted L-arginine analogs, and some of these compounds are useful in reversing pathologies associated with the overproduction of NO (e.g. the hypotension of septic shock). We report here that L-thiocitrulline (gamma-thioureido-L-norvaline) is a potent, stereospecific inhibitor of the constitutive brain and endothelial isoforms of NOS as well as the isoform induced in vascular smooth muscle cells by lipopolysaccharide and interferon-gamma. Steady state kinetic studies show L-thiocitrulline inhibition is competitive with L-arginine (Ki approximately 4-20% of KArgm), indicating that initial binding is as a substrate/product analog. In contrast to L-arginine and N omega-methyl-L-arginine, the prototypic NOS inhibitor, L-thiocitrulline binding elicits a "Type II" difference spectrum, indicating a high spin to low spin transition of the iron in the heme cofactor. This finding suggests that L-thiocitrulline is contributing the sixth ligand to heme iron, probably through the thioureido sulfur. Such interaction with heme iron neither stimulates nor inhibits the direct flavin-mediated cytochrome c reduction activity of the enzyme, but it does inhibit heme-dependent superoxide formation. In vivo, L-thiocitrulline is a potent pressor agent in both normal and endotoxemic rats, the latter finding suggesting utility in treating the hypotension of septic shock.     

Water treatment with silicofluorides and lead toxicity

Toxic metals like lead, manganese, copper and cadmium damage neurons and deregulate neurotransmitters like serotonin and dopamine (which are essential to normal impulse control and learning). Earlier studies show that — controlling for socio‐economic and demographic factors — environmental pollution with lead is a highly significant risk factor in predicting higher rates of crime, attention deficit disorder or hyperactivity, and learning disabilities. Exposure and uptake of lead has been associated with industrial pollution, leaded paint and plumbing systems in old housing, lead residues in soil, dietary habits (such as shortages of calcium and iron), and demographic factors (such as poverty, stress, and minority ethnicity). We report here on an additional “risk co‐factor” making lead and other toxic metals in the environment more dangerous to local residents: the use of silicofluorides as agents in water treatment. The two chemicals in question — fluosilicic acid and sodium silicofluoride — are toxins that, despite claims to the contrary, do not dissociate completely and change water chemistry when used under normal water treatment practices. As a result, water treatment with siliconfluorides apparently functions to increase the cellular uptake of lead. Data from lead screening of over 280,000 children in Massachusetts indicates that silicofluoride usage is associated with significant increases in average lead in children's blood as well as percentage of children with blood lead in excess of 10μg/dL. Consistent with the hypothesized role of silicofluorides as enhancing uptake of lead whatever the source of exposure, children are especially at risk for higher blood lead in those communities with more old housing or lead in excess of 15 ppb in first draw water samples where silicofluorides are also in use. Preliminary findings from county‐level data in Georgia confirm that silicofluoride usage is associated with higher levels of lead in children's blood. In both Massachusetts and Georgia, moreover, behaviors associated with lead nurotoxicity are more frequent in communities using silicofluorides than in comparable localities that do not use these chemicals. Because there has been insufficient animal or human testing of silicofluoride treated water, further study of the effect of silicofluorides is needed to clarify the extent to which these chemicals are risk co‐factors for lead uptake and the hazardous effects it produces.     

Family of G protein {alpha} chains: amphipathic analysis and predicted structure of functional domains

The G proteins transduce hormonal and other signals into regulationof enzymes such as adenylyl cyclase and retinal cGMP phosphodiesterase.Each G protein contains an subunit that binds and hydrolyzesguanine nucleotides and interacts with ß subunitsand specific receptor and effector proteins. Amphipathic andsecondary structure analysis of the primary sequences of fivedifferent chains (bovine _s, _t1 and _t2, mouse _i, and rat _o)predicted the secondary structure of a composite chain (_avg).The chains contain four short regions of sequence homologousto regions in the GDP binding domain of bacterial elongationfactor Tu (EF-Tu). Similarities between the predicted secondarystructures of these regions in _avg and the known secondary structureof EF-Tu allowed us to construct a three-dimensional model ofthe GDP binding domain of _avg. Identification of the GDP bindingdomain of _avg defined three additional domains in the compositepolypeptide. The first includes the amino terminal 41 residuesof _avg, with a predicted am phipathic helical structure; thisdomain may control binding of the chains to the ßcomplex. The second domain, containing predicted ßstrands and helices, several of which are strongly amphipathic,probably contains sequences responsible for interaction of chains with effector enzymes. The predicted structure of thethird domain, containing the carhoxy terminal 100 amino acids,is predominantly ß sheet with an amphipathic helixat the carboxy terminus. We propose that this domain is reponsiblefor receptor binding. Our model should help direct further experimentsinto the structure and function of the G protein chain.     

Development and Validation of a Flowsheet Simulation Model for Neptunium Extraction in an Advanced PUREX Process

An Advanced PUREX process has been developed for separation and recycling of neptunium from spent nuclear fuel. This work presents a new flowsheet simulation model for the extraction of neptunium using centrifugal contactors, where mass transfer is modeled using two-film theory and a linear driving force. Distribution coefficients and neptunium redox reactions are modeled using published models. Mass transfer between the organic and aqueous phases in the phase separation zone is shown to have a negligible effect. The model is applied to a previously tested flowsheet and its predictions are shown to be in good agreement with the experimental results.