Tiny Signals from the Human Brain: Acquisition and Processing of Biomagnetic Fields in Magnetoencephalography

Low-temperature superconductivity plays an important role in some specific biomedical applications, and, in particular, in non-invasive imaging methods of human brain activity. Superconducting magnets are indispensable for functional magnetic resonance imaging (fMRI) which allows functional imaging of the brain with high spatial but poor temporal resolution. Superconducting quantum interference devices (SQUIDs) are the most sensitive magnetic field detectors. Up to a few hundreds of SQUIDs are nowdays used in modern whole-head magnetoencephalography (MEG) systems. They allow tracking brain activation with a superior temporal resolution of milliseconds, which is a quintessential condition for the monitoring of brain dynamics and the understanding of information processing in the human brain. We introduce the prerequisites of MEG data acquisition and briefly review two established methods of biomagnetic signal processing: The concept of signal averaging, and the subsequent source identification as a solution of the biomagnetic inverse problem. Beside these standard techniques, we discuss advanced methods for signal processing in MEG, which take into account the frequency content of the recorded signal. We briefly refer to the prospects of Fourier analysis and wavelet transform in MEG data analysis, and suggest matching pursuit as a promising tool for signal decomposition and reconstruction with high resolution in time-frequency plane.     

Gemcitabine cytotoxicity of human malignant glioma cells: modulation by antioxidants, BCL-2 and dexamethasone

Gemcitabine is a novel antimetabolite drug that acts by multiple mechanisms, including inhibition of ribonucleoside diphosphate reductase, of dCMP deaminase and of dCTP incorporation into DNA and RNA. Here, we report that gemcitabine induces cytotoxic and clonogenic death of 12 human malignant glioma cell lines at clinically relevant concentrations around 1 microM. Gemcitabine is thus approximately 100-fold more active than the congener drug, cytarabine. Gemcitabine cytotoxicity of glioma cells does not require wild-type p53 activity: (i) there was no difference in the susceptibility to gemcitabine between cell lines with wild-type p53 and cell lines with mutant or deleted p53; (ii) ectopic expression of a temperature-sensitive p53 protein either at wild-type (32.5 degrees C) or at mutant (38.5 degrees C) conformation had no significant influence on gemcitabine-induced cell death. Gemcitabine cytotoxicity was unaffected by the antioxidants, N-acetylcysteine and phenyl-N-tert-butyl-alpha-phenylnitrone. There was no correlation between the susceptibility to gemcitabine and the endogenous expression of the B cell lymphoma-2 (BCL-2)-family proteins BCL-2, BCL-XL, myeloid cell leukemia-1 (MCL-1), BCL-2-associated X protein (BAX), BCL-2 homologous antagonist/killer (BAK) and BCL-XS. Ectopic expression of BCL-2 moderately attenuated gemcitabine-induced cell death. Similarly, preexposure to the synthetic steroid, dexamethasone, which is commonly used to control cerebral edema in brain tumor patients, reduced gemcitabine cytotoxicity. We conclude that the clinical evaluation of gemcitabine for the adjuvant chemotherapy of malignant glioma is warranted.     

Time-frequency analysis using the matching pursuit algorithm applied to seizures originating from the mesial temporal lobe

A Spanish-language questionnaire designed for measuring the impact of asthma on quality of life in adults was developed. It was derived, by the application of a rigorous translation protocol, from a previously validated, English-language Asthma Quality of Life (AQL) questionnaire which had been developed in Australia. The aim of this study was to evaluate the psychometric properties of the Spanish AQL questionnaire using a cross-sectional and longitudinal design. Two hundred ninety-four clinically stable subjects with asthma (168 women, mean baseline forced expiratory volume in 1 sec [FEV1] = 85% predicted), aged 17-70, attended for the initial baseline assessment. All subjects completed the AQL questionnaire and a full history and physical examination were performed. The clinical assessment of severity was based on the classification recommended by the Global Initiative on Asthma (GINA). One week after the initial assessment subjects completed the AQL questionnaire for a second time. Six months later, subjects were assessed clinically and completed all the assessment measures at baseline. Principal components analysis of the AQL questionnaire responses at the baseline visit revealed a structure that was almost identical to that seen in the original English-language questionnaire. The questionnaire was shown to be internally consistent (Cronbach's alpha 0.91 for total score and 0.80-0.86 for the four subscales) and repeatable (intraclass correlation coefficient 0.91 for the total scale and 0.78-0.92 for the subscales). The finding of expected strong correlations with the subject's global assessment of severity (p = 0.70) and dyspnea (p = 0.63), a weak inverse correlation with FEV1 (p = -0.17), and good discrimination among the four GINA severity categories (F3,291 = 37.16, p < 0.0001) supports the construct validity of the questionnaire. AQL scores increased with age (p = 0.31) and were higher in women (p < 0.005). The AQL was responsive to both improvement (mean change 1.02, p < 0.0001) and deterioration (mean change -1.13, p < 0.001) in the severity of asthma over a 6-month period. This disease-specific, Spanish-language AQL questionnaire was shown to have sound psychometric properties which make it suitable for use in cross-sectional or longitudinal studies where it is appropriate to assess the impact of asthma on the quality of life of individual patients.     

A Novel Synthesis,Structural, Morphological,and Opto-magnetic Characterizations of Magnetically Separable Spinel Co x Mn1−x Fe2O4 (0 ≤ x ≤ 1) Nano-catalysts

Spinel Co _x Mn_1?x Fe₂O₄ (0≤x≤1) nano- crystals were successfully synthesized by a simple microwave-assisted combustion method. High-resolution scanning electron microscopy (HR-SEM) and transmission electron microscopy (HR-TEM) analysis was used to study the morphological variations and found the particle-like nanocrystal morphologies. Energy dispersive X-ray (EDX) results showed that the composition of the elements were relevant as expected from the combustion synthesis. Powder X-ray diffraction (XRD) analysis showed that all composition was found to have cubic spinel-type structure. Average crystallite size of the samples was found to be in the range of 10.36–21.16 nm. The lattice parameter decreased from 8.478 to 8.432 Å with increasing Co²⁺ content. Fourier transform infrared (FT-IR) spectra showed two strong absorption peaks observed at lower frequency (～435 to ～800 cm^?1), which can be assigned to the M–O (Mn, Co, and Fe) bonds. UV-Visible diffuse reflectance spectroscopy (DRS) shows that the energy band gap of pure MnFe₂O₄ is 1.78 eV and with increase in the Co²⁺ ion, it increases from 1.87 to 2.33 eV. Addition of Co²⁺ in MnFe₂O₄ reduces the particle size, which can be confirmed by the blue shift in the photoluminescence (PL) spectra. Vibrating sample magnetometer (VSM) results that confirmed a weak ferromagnetic behavior for all composition with saturation magnetization values in the range of 50.05 ±04 to 67.09 °03 emu/g. All composition of spinel Co _x Mn_1?x Fe₂O₄ nano-crystals were successfully tested as catalyst for the oxidation of benzyl alcohol to benzaldehyde, which has resulted 87.32 and 94.28 % conversion efficiency of MnFe₂O₄ and Co_0.6Mn_0.4Fe₂O₄, respectively.     

Dexamethasone-mediated protection from drug cytotoxicity: association with p21WAF1/CIP1 protein accumulation?

Dexamethasone (DEX)-mediated inhibition of drug-induced, but not CD95 ligand-induced, apoptosis in malignant glioma cells correlates with wild-type p53 status. Here, we examined mechanisms underlying DEX-mediated protection from apoptosis. DEX did not induce p53 expression in two p53 wild-type cell lines (U87MG, LN-229) and did not alter drug-induced p53 accumulation. Forced expression of temperature-sensitive p53val135 in mutant conformation failed to prevent accumulation of endogenous wild-type p53 but acted in a transdominant negative manner to inhibit p53-mediated, camptothecin-induced p21WAF1/CIP1 expression. p53val135-transfected cells retained responsiveness to DEX at restrictive temperature, suggesting that p53 activity is not required for cytoprotection. Forced expression of wild-type p53val135 abrogated the protective effect of DEX, suggesting redundant cytoprotective effects of DEX and p53. Indeed, DEX induced moderate accumulation of p21WAF1/CIP1 in U87MG, LN-229 and p53 mutant LN-18 cells, but not in p53 mutant LN-308 or T98G cells. LN-18 is also the p53 mutant cell line with the best cytoprotective response to DEX. p21WAF1/CIP1 accumulation occurred in the absence of changes in p21WAF1/CIP1 mRNA expression. Wild-type p53 was not required for this DEX effect since DEX induced p21WAF1/CIP1 accumulation in p53val135-transfected LN-229 cells, too. DEX failed to induce p21WAF1/CIP1 expression or cytoprotection in untransformed rat astrocytes. The same lack of modulation of p21WAF1/CIP1 expression and drug toxicity was observed in p21(+/+), p21(+/-) and p21(-/-) human colon carcinoma cells. Paradoxically, while only p21(+/+) and p21(+/-) mouse embryonic fibroblasts showed enhance p21WAF1/CIP1 levels after exposure to DEX, only p21(-/-) fibroblasts were protected from drug toxicity by DEX. The present study links DEX-mediated protection from cancer chemotherapy to a p53-independent pathway of regulating p21WAF1/CIP1 expression in glioma cells but this effect appears to cell type-specific.     

Insights into the in vitro Anticancer Effects of Diruthenium‐1

The in vitro anticancer activity of the dinuclear trithiolato‐bridged arene ruthenium complex diruthenium‐1 (DiRu‐1) was evaluated against a panel of human cancer cell lines used as in vitro models for hepatocellular carcinoma (HepG2 cells), estrogen‐responsive breast adenocarcinoma (MCF‐7 cells), and triple‐negative breast adenocarcinoma (MDA‐MB‐231 cells). DiRu‐1 is highly cytotoxic to these cell lines, demonstrating half‐maximal inhibitory concentrations (IC₅₀) in the low‐nanomolar range (77±1.4 to 268.2±4.4 nm ). The main molecular mechanisms responsible for the high cytotoxicity of DiRu‐1 against the most responsive MCF‐7 cell line (IC₅₀=77±1.4 nm) were investigated on the basis of the capacity of DiRu‐1 to induce oxidative stress, apoptosis, and DNA damage, and to inhibit the cell cycle and proliferation. The results show that DiRu‐1 triggers caspase‐dependent apoptosis in MCF‐7 cells on both the intrinsic and extrinsic pathways. Moreover, the Ru complex also causes necrosis, mitotic catastrophe, and autophagy. DiRu‐1 increases the intracellular levels of reactive oxygen species (ROS), which play a significant role in its cytotoxicity and pro‐apoptotic activity. An important mechanism of the anticancer activity of DiRu‐1 appears to be the induction of DNA lesions, mainly due to apoptotic DNA fragmentation and cell‐cycle arrest at the G₂/M checkpoint. These changes are correlated with the concentration of DiRu‐1, the duration of the cell treatment, and the post‐treatment time.     

High resolution time-frequency analysis of otoacoustic emissions

High resolution time-frequency analysis of OAE signals evoked by stimuli of different strength was performed by means of the Matching Pursuit algorithm. The method relies on adaptive decomposition of a signal into waveforms of well-defined frequency and time localization. Energy of OAE as a function of time and frequency was evaluated for stimuli strength of 35-80 dB SPL. Dynamic characteristics of the signal were constructed. For strong stimuli decrease of the power of high frequency components was found. Matching Pursuit proved to be a method which offers high resolution parametrisation of OAE in time-frequency space and provides excellent possibilities of investigation of the signal generation mechanisms.