Tyrosine hydroxylase expression in primary cultures of olfactory bulb: role of L-type calcium channels

Sensory activity mediates regulation of tyrosine hydroxylase (TH), the first enzyme in the dopamine biosynthetic pathway, in the rodent olfactory bulb. The current studies established for the first time primary cultures of neonatal mouse olfactory bulb expressing TH and tested whether L-type calcium channels mediate the activity-dependent regulation of the dopamine phenotype. After 1 d in vitro (DIV), a small population of TH-immunostained neurons that lacked extensive processes could be demonstrated. After an additional 2 DIV in serum-free medium, the number of TH neurons had doubled, and they exhibited long interdigitating processes. Membrane depolarization for 48 hr with 50 mM KCl produced a further 2.4-fold increase in the number of TH-immunoreactive neurons compared with control cultures. Increased TH neuron number required at least 36 hr of exposure to KCl. Forskolin, which increases intracellular cAMP levels, induced a 1.5- to 1.6-fold increase in the number of TH-immunostained neurons. Combined treatment with KCl and forskolin was not additive. Nifedipine, an L-type calcium channel blocker, completely prevented the depolarization-mediated increase in TH expression but did not block the response to forskolin. Treatment with Bay K8644, an L-type calcium channel agonist, also significantly increased the number of TH-expressing neurons. Depolarization also induced alterations in neuritic outgrowth, resulting in a stellate versus an elongate morphology that, in contrast, was not prevented by nifedipine. These results are the first demonstration that in vitro, as in vivo, depolarization increases TH expression in olfactory bulb and that L-type calcium channels mediate this activity-dependent regulation of the dopamine phenotype.     

Impact and penetration by L/D ≤ 1 projectiles

Calculations of steel target penetration by L/D ≤ 1 tungsten and tungsten alloy projectiles have been extended to L/D = 1/32 over the velocity range 1.5 to 5 km/s. The ratio of crater to projectile diameter tends to 1 as L/D decreases over this entire velocity range. For impact velocities of 1.5 and 3 km/s, penetration depth normalized by projectile length, P/L, increases with decreasing projectile L/D up to a maximum value and then decreases for still lower L/D. Experiments at impact velocities of 2 and 3 km/s confirm these results. For 5 km/s impact velocity, the calculations show P/L increasing with decreasing projectile L/D over the entire range 1/32 ≤ L/D ≤ 1. The projectile L/D for which the maximum P/L occurs appears to depend on the impact velocity. P/L generally scales with impact velocity as P/L v^f(L/D) where f(L/D) ranges from 0 for a long rod to, we believe, 2 in the limit as projectile L/D approaches zero. The calculations show for 1/8 ≤ L/D ≤ 1/2, P/L v^0.9; for L/D = 1/16, P/L v^1.5; and for L/D = 1/32, the new results give P/L v^1.9.     

Delayed theory combination vs. Nelson-Oppen for satisfiability modulo theories: a comparative analysis

Most state-of-the-art approaches for Satisfiability Modulo Theories $(SMT(\mathcal{T}))$ rely on the integration between a SAT solver and a decision procedure for sets of literals in the background theory $\mathcal{T} (\mathcal{T}{\text {-}}solver)$ . Often $\mathcal{T}$ is the combination $\mathcal{T}_1 \cup \mathcal{T}_2$ of two (or more) simpler theories $(SMT(\mathcal{T}_1 \cup \mathcal{T}_2))$ , s.t. the specific ${\mathcal{T}_i}{\text {-}}solvers$ must be combined. Up to a few years ago, the standard approach to $SMT(\mathcal{T}_1 \cup \mathcal{T}_2)$ was to integrate the SAT solver with one combined $\mathcal{T}_1 \cup \mathcal{T}_2{\text {-}}solver$ , obtained from two distinct ${\mathcal{T}_i}{\text {-}}solvers$ by means of evolutions of Nelson and Oppen’s (NO) combination procedure, in which the ${\mathcal{T}_i}{\text {-}}solvers$ deduce and exchange interface equalities. Nowadays many state-of-the-art SMT solvers use evolutions of a more recent $SMT(\mathcal{T}_1 \cup \mathcal{T}_2)$ procedure called Delayed Theory Combination (DTC), in which each ${\mathcal{T}_i}{\text {-}}solver$ interacts directly and only with the SAT solver, in such a way that part or all of the (possibly very expensive) reasoning effort on interface equalities is delegated to the SAT solver itself. In this paper we present a comparative analysis of DTC vs. NO for $SMT(\mathcal{T}_1 \cup \mathcal{T}_2)$ . On the one hand, we explain the advantages of DTC in exploiting the power of modern SAT solvers to reduce the search. On the other hand, we show that the extra amount of Boolean search required to the SAT solver can be controlled. In fact, we prove two novel theoretical results, for both convex and non-convex theories and for different deduction capabilities of the ${\mathcal{T}_i}{\text {-}}solvers$ , which relate the amount of extra Boolean search required to the SAT solver by DTC with the number of deductions and case-splits required to the ${\mathcal{T}_i}{\text {-}}solvers$ by NO in order to perform the same tasks: (i) under the same hypotheses of deduction capabilities of the ${\mathcal{T}_i}{\text {-}}solvers$ required by NO, DTC causes no extra Boolean search; (ii) using ${\mathcal{T}_i}{\text {-}}solvers$ with limited or no deduction capabilities, the extra Boolean search required can be reduced down to a negligible amount by controlling the quality of the $\mathcal{T}$ -conflict sets returned by the ${\mathcal{T}_i}{\text {-}}solvers$ .     

Modification of human platelet adhesion on biomaterial surfaces by protein preadsorption under static and flow conditions

Biomaterial-induced thrombosis remains one of the main complications of vascular implant devices. Preadsorbed proteins on the biomaterial/blood interface will modify the adhesion and activation of platelets (PTLs) during the initial contact-phase. Our results clearly show that PTL-adherence on biomaterials is influenced not only by protein preadsorption, but also by flow conditions. The covalent coating of TCPS and glass by phosphorylcholine (PC) induces a significant decrease of PTL adhesion but leads to a slight, but nevertheless significant activation of PTL, which was detected by the induction of P-selectin expression using FACS analysis. Methodologically, the visualization of PTL adhesion gave more reliable results for measurement of PTL adhesion than the cell-enzyme immunoassay (EIA) for P-selectin. Human citrated plasma caused an inhibition of PTL. It is probable, that the contained sodium citrate may inhibit PTL adhesion by its calcium ion-binding capacity. The flow experiment as dynamic system is in our view absolutely essential for the evaluation of biomaterials for vascular prosthesis, and is in accordance with the international standards. The results of the experiments also suggest that investigations under static and flow conditions are needed to determine the influence of protein adsorption on mixed blood cell populations, for example, on PTL and PMN mixtures/co-cultures in order to achieve a better simulation of the in vivo situation.     

Purification of molecularly bridged metal nanoparticle arrays by centrifugation and size exclusion chromatography.

Size exclusion chromatography and centrifugation separation protocols were developed and compared for isolating enriched fractions of phenylethynyl-bridged metal nanoparticle dimers and trimers from the monomeric particle starting material. Both methods enabled the isolation of enriched fractions of a desired array without causing significant sample aggregation or replacement of the phenylethynyl bridge. Solutions containing ca. 70% bridged gold dimers were obtained using either method. The further development of methods for separating discrete arrays of covalently bridged nanoparticle homo and hetero structures is expected to help advance our understanding of collective metal particle electronic structure-function relationships.     

Virological treatment failure of protease inhibitor therapy in an unselected cohort of HIV-infected patients

OBJECTIVE: To determine the rate of virological treatment failure with protease inhibitor therapy in unselected patients and to assess underlying risk factors. DESIGN AND SETTING: Retrospective study in two German tertiary care treatment centres. PATIENTS: A total of 198 HIV-infected patients treated with protease inhibitors in 1996. MAIN OUTCOME MEASURES: Levels of HIV RNA 1-6 months after start of treatment; definition of treatment failure of < 1 log10 reduction in plasma HIV RNA within 6 months after starting protease inhibitor therapy; multivariate analysis of risk factors for treatment failures. RESULTS: A total of 226 treatment episodes with protease inhibitors were evaluable (saquinavir, 83; ritonavir, 47; indinavir, 96). The rate of virological treatment failure was 44% (saquinavir, 64%; ritonavir, 38%; indinavir, 30%). In a multivariate analysis, the following independent risk factors for virological failure were found: CD4 cell count, pretreatment with antiretroviral drugs (number), and protease inhibitor (compound). The relative risk reduction for each CD4 cell count increase was 0.997 (P = 0.012), 2.64 for pretreatment with one or two drugs versus no drug (P = 0.05), 2.97 for pretreatment with more than two drugs versus no drug (P = 0.05), and 4.62 for treatment with saquinavir versus indinavir (P = 0.001). CONCLUSION: An unexpectedly high rate of virological treatment failure of protease inhibitor therapy was found in an unselected cohort of HIV-infected patients. Response to antiretroviral combination therapy in normal clinical practice may considerably differ from results of randomized clinical trials. Further studies are warranted to find optimal treatment strategies for both initial and salvage therapy.     

Variation of crater geometry with projectile L/D for L/D ≤ 1

A series of hydrocode calculations and terminal ballistics experiments were performed to investigate the penetration mechanics of projectiles with L/D ≤ 1. Projectile L/D ranged from 1/32 to 1; impact velocity ranged from 1.5 to 5 km/s. Projectiles were tungsten or tungsten alloy, targets were RHA. The paper concentrates on the effect of projectile L/D on the size and geometry of the target crater. Normalized crater depth (or penetration) increases with decreasing projectile L/D and achieves a maximum at about L/D=1/8 for 1.5 km/s and 1/16 for 3 km/s, and then decreases with further decrease in L/D. For 5 km/s, P/L increases with decreasing L/D over the entire range studied. P/L scales with impact velocity as P/L V^f(L/D) where, we believe, f(L/D) approaches 2 as L/D 0. The ratio of crater to projectile diameter D_c/D decreases with decreasing L/D and approaches a value of 1 as L/D approaches zero for all velocities studied. The crater shape measured by P/D_c decreases with decreasing L/D; i.e., as L/D decreases, the crater changes from approximately hemispherical for L/D = 1 to a very shallow disk shape. The kinetic energy required per unit crater volume, KE/V_c, increases with decreasing L/D for L/D < 1/4. That is, cratering efficiency decreases with decreasing projectile L/D. For the impacts studied, KE/V_c increases from about 5 kJ/cm³ to 12 kJ/cm³ as projectile L/D is reduced from 1 to 1/32.     

Principal-components analysis of the equivalence of alternate forms of the Trail Making Test.

One of the methods of evaluating the reliability of alternative forms of assessment instruments is to evaluate the relation of the 2 forms to other measures in a factor analysis. Using this method, the authors investigated the reliability of alternate forms of Trail Making Tests A and B, called Trails C and D. Neuropsychological screening test data were collected from the files of 144 clients referred to a university hospital for neuropsychological evaluations. The tests included Trail Making Tests A, B, C, and D; the Digit Symbol subtest of the Wechsler Adult Intelligence Scale—Revised; and the Stroop Color-Word test. Analyses provided tentative support for the equivalency of the alternative forms of the Trail Making Test. (PsycINFO Database Record (c) 2010 APA, all rights reserved)