Increased expression of the auxiliary beta2-subunit of ventricular L-type Ca2+ channels leads to single-channel activity characteristic of heart failure

BACKGROUND: Increased activity of single ventricular L-type Ca(2+)-channels (L-VDCC) is a hallmark in human heart failure. Recent findings suggest differential modulation by several auxiliary beta-subunits as a possible explanation. METHODS AND RESULTS: By molecular and functional analyses of human and murine ventricles, we find that enhanced L-VDCC activity is accompanied by altered expression pattern of auxiliary L-VDCC beta-subunit gene products. In HEK293-cells we show differential modulation of single L-VDCC activity by coexpression of several human cardiac beta-subunits: Unlike beta(1) or beta(3) isoforms, beta(2a) and beta(2b) induce a high-activity channel behavior typical of failing myocytes. In accordance, beta(2)-subunit mRNA and protein are up-regulated in failing human myocardium. In a model of heart failure we find that mice overexpressing the human cardiac Ca(V)1.2 also reveal increased single-channel activity and sarcolemmal beta(2) expression when entering into the maladaptive stage of heart failure. Interestingly, these animals, when still young and non-failing ("Adaptive Phase"), reveal the opposite phenotype, viz: reduced single-channel activity accompanied by lowered beta(2) expression. Additional evidence for the cause-effect relationship between beta(2)-subunit expression and single L-VDCC activity is provided by newly engineered, double-transgenic mice bearing both constitutive Ca(V)1.2 and inducible beta(2) cardiac overexpression. Here in non-failing hearts induction of beta(2)-subunit overexpression mimicked the increase of single L-VDCC activity observed in murine and human chronic heart failure. CONCLUSIONS: Our study presents evidence of the pathobiochemical relevance of beta(2)-subunits for the electrophysiological phenotype of cardiac L-VDCC and thus provides an explanation for the single L-VDCC gating observed in human and murine heart failure.

EEG reactivity and EEG activity in never-treated acute schizophrenics, measured with spectral parameters and dimensional complexity

Our approaches to the use of EEG studies for the understanding of the pathogenesis of schizophrenic symptoms are presented. The basic assumptions of a heuristic and multifactorial model of the psychobiological brain mechanisms underlying the organization of normal behavior is described and used in order to formulate and test hypotheses about the pathogenesis of schizophrenic behavior using EEG measures. Results from our studies on EEG activity and EEG reactivity (= EEG components of a memory-driven, adaptive, non-unitary orienting response) as analyzed with spectral parameters and "chaotic" dimensionality (correlation dimension) are summarized. Both analysis procedures showed a deviant brain functional organization in never-treated first-episode schizophrenia which, within the framework of the model, suggests as common denominator for the pathogenesis of the symptoms a deviation of working memory, the nature of which is functional and not structural.

Multilead quantitative electroencephalogram profile and cognitive evoked potentials (P300) in healthy subjects after a single dose of olanzapine

RATIONALE: Olanzapine is an atypical antipsychotic drug with a more favourable safety profile than typical antipsychotics with a hitherto unknown topographic quantitative electroencephalogram (QEEG) profile. OBJECTIVES: We investigated electrical brain activity (QEEG and cognitive event related potentials, ERPs) in healthy subjects who received olanzapine. METHODS: Vigilance-controlled, 19-channel EEG and ERP in an auditory odd-ball paradigm were recorded before and 3 h, 6 h and 9 h after administration of either a single dose of placebo or olanzapine (2.5 mg and 5 mg) in ten healthy subjects. QEEG was analysed by spectral analysis and evaluated in nine frequency bands. For the P300 component in the odd-ball ERP, the amplitude and latency was analysed. Statistical effects were tested using a repeated-measurement analysis of variance. RESULTS: For the interaction between time and treatment, significant effects were observed for theta, alpha-2, beta-2 and beta-4 frequency bands. The amplitude of the activity in the theta band increased most significantly 6 h after the 5-mg administration of olanzapine. A pronounced decrease of the alpha-2 activity especially 9 h after 5 mg olanzapine administration could be observed. In most beta frequency bands, and most significantly in the beta-4 band, a dose-dependent decrease of the activity beginning 6 h after drug administration was demonstrated. Topographic effects could be observed for the beta-2 band (occipital decrease) and a tendency for the alpha-2 band (frontal increase and occipital decrease), both indicating a frontal shift of brain electrical activity. There were no significant changes in P300 amplitude or latency after drug administration. Conclusion: QEEG alterations after olanzapine administration were similar to EEG effects gained by other atypical antipsychotic drugs, such as clozapine. The increase of theta activity is comparable to the frequency distribution observed for thymoleptics or antipsychotics for which treatment-emergent somnolence is commonly observed, whereas the decrease of beta activity observed after olanzapine administration is not characteristic for these drugs. There were no clear signs for an increased cerebral excitability after a single-dose administration of 2.5 mg and 5 mg olanzapine in healthy controls.

Determination of histopathological tumor grade in neuroepithelial brain tumors by using spectral pattern analysis of in vivo spectroscopic data

OBJECT: In this study, 1H magnetic resonance (MR) spectroscopy was prospectively tested as a reliable method for presurgical grading of neuroepithelial brain tumors. METHODS: Using a database of tumor spectra obtained in patients with histologically confirmed diagnoses, 94 consecutive untreated patients were studied using single-voxel 1H spectroscopy (point-resolved spectroscopy; TE 135 msec, TE 135 msec, TR 1500 msec). A total of 90 tumor spectra obtained in patients with diagnostic 1H MR spectroscopy examinations were analyzed using commercially available software (MRUI/VARPRO) and classified using linear discriminant analysis as World Health Organization (WHO) Grade I/II, WHO Grade III, or WHO Grade IV lesions. In all cases, the classification results were matched with histopathological diagnoses that were made according to the WHO classification criteria after serial stereotactic biopsy procedures or open surgery. Histopathological studies revealed 30 Grade I/II tumors, 29 Grade III tumors, and 31 Grade IV tumors. The reliability of the histological diagnoses was validated considering a minimum postsurgical follow-up period of 12 months (range 12-37 months). Classifications based on spectroscopic data yielded 31 tumors in Grade I/II, 32 in Grade III, and 27 in Grade IV. Incorrect classifications included two Grade II tumors, one of which was identified as Grade III and one as Grade IV; two Grade III tumors identified as Grade II; two Grade III lesions identified as Grade IV; and six Grade IV tumors identified as Grade III. Furthermore, one glioblastoma (WHO Grade IV) was classified as WHO Grade I/II. This represents an overall success rate of 86%, and a 95% success rate in differentiating low-grade from high-grade tumors. CONCLUSIONS: The authors conclude that in vivo 1H MR spectroscopy is a reliable technique for grading neuroepithelial brain tumors.

Computer algebra for x-ray spectral reconstruction between 6 and 25 MV

A previously presented algorithm for the reconstruction of bremsstrahlung spectra from transmission data has been implemented into MATHEMATICA. Spectra vectorial algebra has been used to solve the matrix system A * F = T. The new implementation has been tested by reconstructing photon spectra from transmission data acquired in narrow beam conditions, for nominal energies of 6, 15, and 25 MV. The results were in excellent agreement with the original calculations. Our implementation has the advantage to be based on a well-tested mathematical kernel. Furthermore it offers a comfortable user interface.

Spectral waveform analysis of intranodal arterial blood flow in abnormally large superficial lymph nodes in dogs

Objective-To evaluate pulsed-wave Doppler spectral parameters as a method for distinguishing between neoplastic and inflammatory peripheral lymphadenopathy in dogs. Sample Population-40 superficial lymph nodes from 33 dogs with peripheral lymphadenopathy. Procedures-3 Doppler spectral tracings were recorded from each node. Spectral Doppler analysis including assessment of the resistive index, peak systolic velocity-to-end diastolic velocity (S:D) ratio, diastolic notch velocity-to-peak systolic velocity (N:S) ratio, and end diastolic velocity-to-diastolic notch velocity ratio was performed for each tracing. Several calculation methods were used to determine the Doppler indices for each lymph node. After the ultrasonographic examination, fine needle aspirates or excisional biopsy specimens of the examined lymph nodes were obtained, and lymphadenopathy was classified as either inflammatory or neoplastic (lymphomatous or metastatic) via cytologic or histologic examination. Results of Doppler analysis were compared with cytologic or histopathologic findings. Results-The Doppler index with the highest diagnostic accuracy was the S:D ratio calculated from the first recorded tracing; a cutoff value of 3.22 yielded sensitivity of 91%, specificity of 100%, and negative predictive value of 89% for detection of neoplasia. Overall diagnostic accuracy was 95%. At a sensitivity of 100%, the most accurate index was the N:S ratio calculated from the first recorded tracing; a cutoff value of 0.45 yielded specificity of 67%, positive predictive value of 81%, and overall diagnostic accuracy of 86.5%. Conclusions and Clinical Relevance-Results suggested that noninvasive Doppler spectral analysis may be useful in the diagnosis of neoplastic versus inflammatory peripheral lymphadenopathy in dogs.

Visual and quantitative electroencephalographic analysis of healthy young and adult cats under medetomidine sedation

A study was designed to investigate the effect of medetomidine sedation on quantitative electroencephalography (q-EEG) in healthy young and adult cats to determine objective guidelines for diagnostic EEG recordings and interpretation. Preliminary visual examination of EEG recordings revealed high-voltage low-frequency background activity. Spindles, k-complexes and vertex sharp transients characteristic of sleep or sedation were superimposed on a low background activity. Neither paroxysmal activity nor EEG burst-suppression were observed. The spectral analysis of q-EEG included four parameters, namely, relative power (%), and mean, median and peak frequency (Hz) of all four frequency bands (delta, theta, alpha and beta). The findings showed a prevalence of slow delta and theta rhythms as opposed to fast alpha and beta rhythms in both young (group A) and adult (group B) cats. A posterior gradient was reported for the theta band and an anterior gradient for the alpha and beta bands in both groups, respectively. The relative power value in group B compared to group A was significantly higher for theta, alpha and beta bands, and lower for the delta band. The mean and median frequency values in group B was significantly higher for delta, theta and beta bands and lower for the alpha band. The study has shown that a medetomidine sedation protocol for feline EEG may offer a method for investigating bio-electrical cortical activity. The use of q-EEG analysis showed a decrease in high frequency bands and increased activity of the low frequency band in healthy cats under medetomidine sedation.

Quantitative assessment of soil parameters in Western Tajikistan using a soil spectral library approach

Soil degradation is a major problem in the agriculturally dominated country of Tajikistan, which makes it necessary to determine and monitor the state of soils. For this purpose a soil spectral library was established as it enables the determination of soil properties with relatively low costs and effort. A total of 1465 soil samples were collected from three 10x10 km test sites in western Tajikistan. The diffuse reflectance of the samples was measured with a FieldSpec PRO FR from ASD in the spectral range from 380 to 2500 nm in laboratory. 166 samples were finally selected based on their spectral information and analysed on total C and N, organic C, pH, CaCO₃, extractable P, exchangeable Ca, Mg and K, and the fractions clay, silt and sand. Multiple linear regression was used to set up the models. Two third of the chemically analysed samples were used to calibrate the models, one third was used for hold-out validation. Very good prediction accuracy was obtained for total C (R² = 0.76, RMSEP = 4.36 g kg⁻¹), total N (R² = 0.83, RMSEP = 0.30 g kg⁻¹) and organic C (R² = 0.81, RMSEP = 3.30 g kg⁻¹), good accuracy for pH (R² = 0.61, RMSEP = 0.157) and CaCO3(R² = 0.72, RMSEP = 4.63 %). No models could be developed for extractable P, exchangeable Ca, Mg and K, and the fractions clay, silt and sand. It can be concluded that the spectral library approach has a high potential to substitute standard laboratory methods where rapid and inexpensive analysis is required.

Early autonomic dysfunction in patients with diabetes mellitus assessed by spectral analysis of heart rate and blood pressure variability

Patients with diabetes mellitus (DM) often have alterations of the autonomic nervous system (ANS), even early in their disease course. Previous research has not evaluated whether these changes may have consequences on adaptation mechanisms in DM, e.g. to mental stress. We therefore evaluated whether patients with DM who already had early alterations of the ANS reacted with an abnormal regulatory pattern to mental stress. We used the spectral analysis technique, known to be valuable and reliable in the investigation of disturbances of the ANS. We investigated 34 patients with DM without clinical evidence of ANS dysfunction (e.g. orthostatic hypotension) and 44 normal control subjects (NC group). No patients on medication known to alter ANS responses were accepted. The investigation consisted of a resting state evaluation and a mental stress task (BonnDet). In basal values, only the 21 patients with type 2 DM were different in respect to body mass index and systolic blood pressure. In the study parameters we found significantly lower values in resting and mental stress spectral power of mid-frequency band (known to represent predominantly sympathetic influences) and of high-frequency and respiration bands (known to represent parasympathetic influences) in patients with DM (types 1 and 2) compared with NC group (5.3 +/- 1.2 ms2 vs. 6.1 +/- 1.3 ms2, and 5.5 +/- 1.6 ms2 vs. 6.2 +/- 1.5 ms2, and 4.6 +/- 1.7 ms2 vs. 6.2 +/- 1.5 ms2, for resting values respectively; 4.7 +/- 1.4 ms2 vs. 5.9 +/- 1.2 ms2, and 4.6 +/- 1.9 ms2 vs. 5.6 +/- 1.7 ms2, and 3.7 +/- 2.1 ms2 vs. 5.6 +/- 1.7 ms2, for stress values respectively; M/F ratio 6/26 vs. 30/14). These differences remained significant even when controlled for age, sex, and body weight. However, patients with DM type 2 (and significantly higher body weight) showed only significant values in mental stress modulus values. There were no specific group effects in the patients with DM in adaptation mechanisms to mental stress compared with the NC group. These findings demonstrate that power spectral examinations at rest are sufficiently reliable to diagnose early alterations in ANS in patients with DM. The spectral analysis technique is sensitive and reliable in investigation of ANS in patients with DM without clinically symptomatic autonomic dysfunction.

RF-sputter fabrication of magnetic garnet thin films and simulation modeling for 1-D magnetic photonic crystal waveguide devices

One dimensional magnetic photonic crystals (1D-MPC) are promising structures for integrated optical isolator applications. Rare earth substituted garnet thin films with proper Faraday rotation are required to fabricate planar 1D-MPCs. In this thesis, flat-top response 1D-MPC was proposed and spectral responses and Faraday rotation were modeled. Bismuth substituted iron garnet films were fabricated by RF magnetron sputtering and structures, compositions, birefringence and magnetooptical properties were studied. Double layer structures for single mode propagation were also fabricated by sputtering for the first time. Multilayer stacks with multiple defects (phase shift) composed of Ce-YIG and GGG quarter-wave plates were simulated by the transfer matrix method. The transmission and Faraday rotation characteristics were theoretically studied. It is found that flat-top response, with 100% transmission and near 45o rotation is achievable by adjusting the inter-defect spacing, for film structures as thin as 30 to 35 μm. This is better than 3-fold reduction in length compared to the best Ce-YIG films for comparable rotations, thus allows a considerable reduction in size in manufactured optical isolators. Transmission bands as wide as 7nm were predicted, which is considerable improvement over 2 defects structure. Effect of repetition number and ratio factor on transmission and Faraday rotation ripple factors for the case of 3 and 4 defects structure has been discussed. Diffraction across the structure corresponds to a longer optical path length. Thus the use of guided optics is required to minimize the insertion losses in integrated devices. This part is discussed in chapter 2 in this thesis. Bismuth substituted iron garnet thin films were prepared by RF magnetron sputtering. We investigated or measured the deposition parameters optimization, crystallinity, surface morphologies, composition, magnetic and magnetooptical properties. A very high crystalline quality garnet film with smooth surface has been heteroepitaxially grown on (111) GGG substrate for films less than 1μm. Dual layer structures with two distinct XRD peaks (within a single sputtered film) start to develop when films exceed this thickness. The development of dual layer structure was explained by compositional gradient across film thickness, rather than strain gradient proposed by other authors. Lower DC self bias or higher substrate temperature is found to help to delay the appearance of the 2nd layer. The deposited films show in-plane magnetization, which is advantageous for waveguide devices application. Propagation losses of fabricated waveguides can be decreased by annealing in an oxygen atmosphere from 25dB/cm to 10dB/cm. The Faraday rotation at λ=1.55μm were also measured for the waveguides. FR is small (10° for a 3mm long waveguide), due to the presence of linear birefringence. This part is covered in chapter 4. We also investigated the elimination of linear birefringence by thickness tuning method for our sputtered films. We examined the compressively and tensilely strained films and analyze the photoelastic response of the sputter deposited garnet films. It has been found that the net birefringence can be eliminated under planar compressive strain conditions by sputtering. Bi-layer GGG on garnet thin film yields a reduced birefringence. Temperature control during the sputter deposition of GGG cover layer is critical and strongly influences the magnetization and birefringence level in the waveguide. High temperature deposition lowers the magnetization and increases the linear birefringence in the garnet films. Double layer single mode structures fabricated by sputtering were also studied. The double layer, which shows an in-plane magnetization, has an increased RMS roughness upon upper layer deposition. The single mode characteristic was confirmed by prism coupler measurement. This part is discussed in chapter 5.

Detecting changes in surface moisture and water table position with spectral changes in surface vegetation in northern peatlands

Due to warmer and drier conditions, wildland fire has been increasing in extent into peatland ecosystems during recent decades. As such, there is an increasing need for broadly applicable tools to detect surface peat moisture, in order to ascertain the susceptibility of peat burning, and the vulnerability of deep peat consumption in the event of a wildfire. In this thesis, a field portable spectroradiometer was used to measure surface reflectance of two Sphagnum moss dominated peatlands. Relationships were developed correlating spectral indices to surface moisture as well as water table position. Spectral convolutions were also applied to the high resolution spectra to represent spectral sensitivity of earth observing sensors. Band ratios previously used to monitor surface moisture with these sensors were assessed. Strong relationships to surface moisture and water table position are evident for both the narrowband indices as well as broadened indices. This study also found a dependence of certain spectral relationships on changes in vegetation cover by leveraging an experimental vegetation manipulation. Results indicate broadened indices employing the 1450-1650 nm region may be less stable under changing vegetation cover than those located in the 1200 nm region.

Morphologic changes in patients with geographic atrophy assessed with a novel spectral OCT-SLO combination

To investigate the appearance of geographic atrophy in high-resolution optical coherence tomography (OCT) images, the fundus autofluorescence (FAF) pattern, and infrared images simultaneously recorded with a novel combined OCT-scanning laser ophthalmology (SLO) system.

Visual and spectral analysis of sleep EEG in acute hemispheric stroke

BACKGROUND: Reports on the effects of focal hemispheric damage on sleep EEG are rare and contradictory. PATIENTS AND METHODS: Twenty patients (mean age +/- SD 53 +/- 14 years) with a first acute hemispheric stroke and no sleep apnea were studied. Stroke severity [National Institute of Health Stroke Scale (NIHSS)], volume (diffusion-weighted brain MRI), and short-term outcome (Rankin score) were assessed. Within the first 8 days after stroke onset, 1-3 sleep EEG recordings per patient were performed. Sleep scoring and spectral analysis were based on the central derivation of the healthy hemisphere. Data were compared with those of 10 age-matched and gender-matched hospitalized controls with no brain damage and no sleep apnea. RESULTS: Stroke patients had higher amounts of wakefulness after sleep onset (112 +/- 53 min vs. 60 +/- 38 min, p < 0.05) and a lower sleep efficiency (76 +/- 10% vs. 86 +/- 8%, p < 0.05) than controls. Time spent in slow-wave sleep (SWS) and rapid eye movement (REM) sleep and total sleep time were lower in stroke patients, but differences were not significant. A positive correlation was found between the amount of SWS and stroke volume (r = 0.79). The slow-wave activity (SWA) ratio NREM sleep/wakefulness was lower in patients than in controls (p < 0.05), and correlated with NIHSS (r = -0.47). CONCLUSION: Acute hemispheric stroke is accompanied by alterations of sleep EEG over the healthy hemisphere that correlate with stroke volume and outcome. The increased SWA during wakefulness and SWS over the healthy hemisphere contralaterally to large strokes may reflect neuronal hypometabolism induced transhemispherically (diaschisis).