Expression of the proto-oncogene c-fos in three-dimensional fetal brain cell cultures and the lack of correlation with maturation-inducing stimuli.

Previous work has shown that aggregating fetal brain cell cultures are able to attain a highly differentiated state, and that their development is greatly enhanced by growth and/or differentiation factors such as epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and the protein kinase C-activating tumor promoter mezerein. The present study shows that in these 3-dimensional cultures the peptide growth factors EGF and bFGF as well as mezerein are able to induce the expression of the proto-oncogene c-fos. This induction was rapid and transient, in good agreement with observations reported from a wide variety of cell types in vitro. The maximal levels of c-fos mRNA found after stimulation were low in immature cultures and increased greatly as maturation progressed. Of the three factors tested, mezerein was the most potent inducer of c-fos. In contrast to the peptide growth factors EGF and bFGF which were found to induce c-fos only in glial cells, mezerein was stimulatory in glial cells as well as in neurons. A similar cell type specificity has been observed previously for the maturation-enhancing response in immature aggregate cultures. However, in the present study no correlation was found between the degree of c-fos induction and the extent of the maturation-enhancing stimulation. Immature cultures known to be most sensitive and responsive to these maturation-enhancing agents required relatively high doses of peptide growth factors for the induction of c-fos, and the maximal levels of c-fos mRNA elicited were much lower than those in differentiated cultures which did not show any long-term response to these stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Systematic study of the static electrical properties of the CO molecule: influence of the basis set size and correlation energy

The influence of the basis set size and the correlation energy in the static electrical properties of the CO molecule is assessed. In particular, we have studied both the nuclear relaxation and the vibrational contributions to the static molecular electrical properties, the vibrational Stark effect (VSE) and the vibrational intensity effect (VIE). From a mathematical point of view, when a static and uniform electric field is applied to a molecule, the energy of this system can be expressed in terms of a double power series with respect to the bond length and to the field strength. From the power series expansion of the potential energy, field-dependent expressions for the equilibrium geometry, for the potential energy and for the force constant are obtained. The nuclear relaxation and vibrational contributions to the molecular electrical properties are analyzed in terms of the derivatives of the electronic molecular properties. In general, the results presented show that accurate inclusion of the correlation energy and large basis sets are needed to calculate the molecular electrical properties and their derivatives with respect to either nuclear displacements or/and field strength. With respect to experimental data, the calculated power series coefficients are overestimated by the SCF, CISD, and QCISD methods. On the contrary, perturbation methods (MP2 and MP4) tend to underestimate them. In average and using the 6-311 + G(3df) basis set and for the CO molecule, the nuclear relaxation and the vibrational contributions to the molecular electrical properties amount to 11.7%, 3.3%, and 69.7% of the purely electronic μ, α, and β values, respectively

Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity.

Resistance to alkylating agents via direct DNA repair by O(6)-methylguanine methyltransferase (MGMT) remains a significant barrier to the successful treatment of patients with malignant glioma. The relative expression of MGMT in the tumor may determine response to alkylating agents, and epigenetic silencing of the MGMT gene by promoter methylation plays an important role in regulating MGMT expression in gliomas. MGMT promoter methylation is correlated with improved progression-free and overall survival in patients treated with alkylating agents. Strategies to overcome MGMT-mediated chemoresistance are being actively investigated. These include treatment with nontoxic pseudosubstrate inhibitors of MGMT, such as O(6)-benzylguanine, or RNA interference-mediated gene silencing of MGMT. However, systemic application of MGMT inhibitors is limited by an increase in hematologic toxicity. Another strategy is to deplete MGMT activity in tumor tissue using a dose-dense temozolomide schedule. These alternative schedules are well tolerated; however, it remains unclear whether they are more effective than the standard dosing regimen or whether they effectively deplete MGMT activity in tumor tissue. Of note, not all patients with glioblastoma having MGMT promoter methylation respond to alkylating agents, and even those who respond will inevitably experience relapse. Herein we review the data supporting MGMT as a major mechanism of chemotherapy resistance in malignant gliomas and describe ongoing studies that are testing resistance-modulating strategies.

Schizophrenia connectivity: correlation between cognitive deficits and reduced thalamo-cortical fibers

Introduction: Schizophrenia is associated with multiple neuropsychological dysfunctions, such as disturbances of attention, memory, perceptual functioning, concept formation and executive processes. These cognitive functions are reported to depend on the integrity of the prefrontal and thalamo-prefrontal circuits. Multiple lines of evidence suggest that schizophrenia is related to abnormalities in neural circuitry and impaired structural connectivity. Here, we report a preliminary case-control study that showed a correlation between thalamo-frontal connections and several cognitive functions known to be impaired in schizophrenia. Materials and Methods: We investigated 9 schizophrenic patients (DSM IV criteria, Diagnostic Interview for Genetic Studies) and 9 age and sex matched control subjects. We obtained from each volunteer a DT-MRI dataset (3 T, _ _ 1,000 s/mm2), and a high resolution anatomic T1. The thalamo- frontal tracts are simulated with DTI tractography on these dataset, a method allowing inference of the main neural fiber tracks from Diffusion MRI data. In order to see an eventual correlation with the thalamo-frontal connections, every subject performs a battery of neuropsychological tests including computerized tests of attention (sustained attention, selective attention and reaction time), working memory tests (Plane test and the working memory sub-tests of the Wechsler Adult Intelligence Scale), a executive functioning task (Tower of Hanoï) and a test of visual binding abilities. Results: In a pilot case-control study (patients: n _ 9; controls: n _ 9), we showed that this methodology is appropriate and giving results in the excepted range. Considering the relation of the connectivity density and the neuropsychological data, a correlation between the number of thalamo- frontal fibers and the performance in the Tower of Hanoï was observed in the patients (Pearson correlation, r _ 0.76, p _ 0.05) but not in control subjects. In the most difficult item of the test, the least number of fibers corresponds to the worst performance of the test (fig. 2, number of supplementary movements of the elements necessary to realize the right configuration). It's interesting to note here that in an independent study, we showed that schizophrenia patients (n _ 32) perform in the most difficult item of the Tower of Hanoï (Mann-Whitney, p _ 0.005) significantly worse than control subjects (n _ 29). This has been observed in several others neuropsychological studies. Discussion: This pilot study of schizophrenia patients shows a correlation between the number of thalam-frontal fibers and the performance in the Tower of Hanoï, which is a planning and goal oriented actions task known to be associated with frontal dysfonction. This observation is consistent with the proposed impaired connectivity in schizophrenia. We aim to pursue the study with a larger sample in order to determine if other neuropsychological tests may be associated with the connectivity density.

Correlation of Der p 2 T-cell responses with clinical characteristics of children allergic to house dust mite.

BACKGROUND: An understanding of the mechanisms responsible for the development and maintenance of allergic inflammation and their clinical implications is needed to develop specific and successful treatment for allergy. OBJECTIVES: To characterize in vitro T-cell responses to Der p 2, one of the major allergens of house dust mite (HDM), and investigate potential correlations between clinical and laboratory parameters. METHODS: Forty-two patients monosensitized to HDM and 10 age-matched, healthy children were studied. Dendritic cells pulsed with Der p 2 were used to stimulate autologous CD14(-) cells. Der p 2-specific T-cell activation markers, proliferation, and cytokine production profiles were examined. RESULTS: Der p 2-specific T-cell activation markers, proliferation, and T(H)2 cytokine production were significantly higher in HDM patients compared with healthy controls. Moreover, a significant correlation between proliferation and T(H)2 cytokine production was observed. Within the allergic group, skin reaction to HDM was significantly stronger in patients with a Der p 2-specific T-cell response. Levels of HDM-specific IgE directly correlated with interleukin 5 and interleukin 13 levels and with skin prick test results and, ultimately, with the patient's family history of allergy. Furthermore, the presence of atopic march correlated with T-cell proliferation. CONCLUSION: We found that, in HDM patients, Der p 2-specific T(H)2 responses, promoted by autologous dendritic cells in vitro, correlate with clinical parameters.

Diagnostic performance of CT-arthrography and 1.5T MR-arthrography for the assessment of glenohumeral joint cartilage: a comparative study with arthroscopic correlation.

PURPOSE: To compare the diagnostic performance of multi-detector CT arthrography (CTA) and 1.5-T MR arthrography (MRA) in detecting hyaline cartilage lesions of the shoulder, with arthroscopic correlation. PATIENTS AND METHODS: CTA and MRA prospectively obtained in 56 consecutive patients following the same arthrographic procedure were independently evaluated for glenohumeral cartilage lesions (modified Outerbridge grade ≥2 and grade 4) by two musculoskeletal radiologists. The cartilage surface was divided in 18 anatomical areas. Arthroscopy was taken as the reference standard. Diagnostic performance of CTA and MRA was compared using ROC analysis. Interobserver and intraobserver agreement was determined by κ statistics. RESULTS: Sensitivity and specificity of CTA varied from 46.4 to 82.4 % and from 89.0 to 95.9 % respectively; sensitivity and specificity of MRA varied from 31.9 to 66.2 % and from 91.1 to 97.5 % respectively. Diagnostic performance of CTA was statistically significantly better than MRA for both readers (all p ≤ 0.04). Interobserver agreement for the evaluation of cartilage lesions was substantial with CTA (κ = 0.63) and moderate with MRA (κ = 0.54). Intraobserver agreement was almost perfect with both CTA (κ = 0.94-0.95) and MRA (κ = 0.83-0.87). CONCLUSION: The diagnostic performance of CTA and MRA for the detection of glenohumeral cartilage lesions is moderate, although statistically significantly better with CTA. KEY POINTS: ? CTA has moderate diagnostic performance for detecting glenohumeral cartilage substance loss. ? MRA has moderate diagnostic performance for detecting glenohumeral cartilage substance loss. ? CTA is more accurate than MRA for detecting cartilage substance loss.

Micro-Raman study of stress distribution in local isolation structures and correlation with transmission electron microscopy

Stress in local isolation structures is studied by micro‐Raman spectroscopy. The results are correlated with predictions of an analytical model for the stress distribution and with cross‐sectional transmission electron microscopy observations. The measurements are performed on structures on which the Si3N4 oxidation mask is still present. The influence of the pitch of the periodic local isolation pattern, consisting of parallel lines, the thickness of the mask, and the length of the bird"s beak on the stress distribution are studied. It is found that compressive stress is present in the Si substrate under the center of the oxidation mask lines, with a magnitude dependent on the width of the lines. Large tensile stress is concentrated under the bird"s beak and is found to increase with decreasing length of the bird"s beak and with increasing thickness of the Si3N4 film.

Precise U-Pb age constraints for end-Triassic mass extinction, its correlation to volcanism and Hettangian post-extinction recovery

New precise zircon U-Pb ages are proposed for the Triassic-Jurassic (Rhetian-Hettangian) and the Hettangian-Sinemurian boundaries, The ages were obtained by ID-TIMS dating of single chemical-abraded zircons from volcanic ash layers within the Pucara Group, Aramachay Formation in the Utcubamba valley, northern Peru. Ash layers situated between last and first occurrences of boundary-defining ammonites yielded Pb-206/U-238 ages of 201.58 +/- 0.17/0.28 Ma (95% c.l., uncertainties without/with decay constant errors, respectively) for the Triassic-Jurassic and of 199.53 +/- 0.19/0.29 Ma for the Hettangian-Sinemurian boundaries. The former is established on a tuff located 1 m above the last local occurrence of the topmost Triassic genus Choristoceras, and 5 m below the Hettangian genus Psiloceras. The latter sample was obtained from a tuff collected within the Badouxia canadensis beds. Our new ages document total duration of the Hettagian of no more than c. 2 m.y., which has fundamental implications for the interpretation and significance of the ammonite recovery after the topmost Triassic extinction. The U-Pb age is about 0.8 +/- 0.5% older than Ar-40-Ar-39 dates determined on flood basalts of the Central Atlantic Magmatic Province (CAMP). Given the widely accepted hypothesis that inaccuracies in the K-40 decay constants or physical constants create a similar bias between the two dating methods, our new U-Pb zircon age determination for the T/J boundary corroborates the hypothesis that the CAMP was emplaced at the same time and may be responsible for a major climatic turnover and mass extinction. The zircon Pb-206/U-238 age for the T/J boundary is marginally older than the North Mountain Basalt (Newark Supergroup, Nova Scotia, Canada), which has been dated at 201.27 +/- 0.06 Ma [Schoene et al., 2006. Geochim. Cosmochim. Acta 70, 426-445]. It will be important to look for older eruptions of the CAMP and date them precisely by U-Pb techniques while addressing all sources of systematic uncertainty to further test the hypothesis of volcanic induced climate change leading to extinction. Such high-precision, high-accuracy data will be instrumental for constraining the contemporaneity of geological events at a 100 kyr level. (C) 2007 Elsevier B.V. All rights reserved.

Static dipole polarizability of alkali-metal clusters: Electronic exchange and correlation effects

Nonlocal approximations for the electronic exchange and correlation effects are used to compute, within density-functional theory, the polarizability and surface-plasma frequencies of small jelliumlike alkali-metal clusters. The results are compared with those obtained using the local-density approximation and with available experimental data, showing the relevance of these effects in obtaining an accurate description of the surface response of metallic clusters.

Intensity correlation function of dye lasers: Short-time behavior

We propose an equation to calculate the intensity correlation function of a dye-laser model with a pump parameter subject to finite-bandwidth fluctuations. The equation is valid, in the weak-noise limit, for all times. It incorporates novel non-Markovian features. Results are given for the short-time behavior of the correlation function. It exhibits a characteristic initial plateau. Our findings are supported by a numerical simulation of the model.