Topographic time-frequency decomposition of the EEG

Frequency-transformed EEG resting data has been widely used to describe normal and abnormal brain functional states as function of the spectral power in different frequency bands. This has yielded a series of clinically relevant findings. However, by transforming the EEG into the frequency domain, the initially excellent time resolution of time-domain EEG is lost. The topographic time-frequency decomposition is a novel computerized EEG analysis method that combines previously available techniques from time-domain spatial EEG analysis and time-frequency decomposition of single-channel time series. It yields a new, physiologically and statistically plausible topographic time-frequency representation of human multichannel EEG. The original EEG is accounted by the coefficients of a large set of user defined EEG like time-series, which are optimized for maximal spatial smoothness and minimal norm. These coefficients are then reduced to a small number of model scalp field configurations, which vary in intensity as a function of time and frequency. The result is thus a small number of EEG field configurations, each with a corresponding time-frequency (Wigner) plot. The method has several advantages: It does not assume that the data is composed of orthogonal elements, it does not assume stationarity, it produces topographical maps and it allows to include user-defined, specific EEG elements, such as spike and wave patterns. After a formal introduction of the method, several examples are given, which include artificial data and multichannel EEG during different physiological and pathological conditions.

High frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral cortex: EEG topography during waking and subsequent sleep.

Repetitive transcranial magnetic stimulation (rTMS) is a novel research tool in neurology and psychiatry. It is currently being evaluated as a conceivable alternative to electroconvulsive therapy for the treatment of mood disorders. Eight healthy young (age range 21-25 years) right-handed men without sleep complaints participated in the study. Two sessions at a 1-week interval, each consisting of an adaptation night (sham stimulation) and an experimental night (rTMS in the left dorsolateral prefrontal cortex or sham stimulation; crossover design), were scheduled. In each subject, 40 trains of 2-s duration of rTMS (inter-train interval 28 s) were applied at a frequency of 20 Hz (i.e. 1600 pulses per session) and at an intensity of 90% of the motor threshold. Stimulations were scheduled 80 min before lights off. The waking EEG was recorded for 10-min intervals approximately 30 min prior to and after the 20-min stimulations, and polysomnographic recordings were obtained during the subsequent sleep episode (23.00-07.00 h). The power spectra of two referential derivations, as well as of bipolar derivations along the antero-posterior axis over the left and right hemispheres, were analyzed. rTMS induced a small reduction of sleep stage 1 (in min and percentage of total sleep time) over the whole night and a small enhancement of sleep stage 4 during the first non-REM sleep episode. Other sleep variables were not affected. rTMS of the left dorsolateral cortex did not alter the topography of EEG power spectra in waking following stimulation, in the all-night sleep EEG, or during the first non-REM sleep episode. Our results indicate that a single session of rTMS using parameters like those used in depression treatment protocols has no detectable side effects with respect to sleep in young healthy males.

Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent

There is established clinical evidence for differences in drug response, cure rates and survival outcomes between different ethnic populations, but the causes are poorly understood. Differences in frequencies of functional genetic variants in key drug response and metabolism genes may significantly influence drug response differences in different populations. To assess this, we genotyped 1330 individuals of African (n=372) and European (n=958) descent for 4535 single-nucleotide polymorphisms in 350 key drug absorption, distribution, metabolism, elimination and toxicity genes. Important and remarkable differences in the distribution of genetic variants were observed between Africans and Europeans and among the African populations. These could translate into significant differences in drug efficacy and safety profiles, and also in the required dose to achieve the desired therapeutic effect in different populations. Our data points to the need for population-specific genetic variation in personalizing medicine and care.

Active immunosurveillance in the tumor microenvironment of colorectal cancer is associated with low frequency tumor budding and improved outcome.

Tumor budding (single tumor cells or small tumor cell clusters) at the invasion front of colorectal cancer (CRC) is an adverse prognostic indicator linked to epithelial-mesenchymal transition. This study characterized the immunogenicity of tumor buds by analyzing the expression of the major histocompatibility complex (MHC) class I in the invasive tumor cell compartment. We hypothesized that maintenance of a functional MHC-I antigen presentation pathway, activation of CD8+ T-cells, and release of antitumoral effector molecules such as cytotoxic granule-associated RNA binding protein (TIA1) in the tumor microenvironment can counter tumor budding and favor prolonged patient outcome. Therefore, a well-characterized multipunch tissue microarray of 220 CRCs was profiled for MHC-I, CD8, and TIA1 by immunohistochemistry. Topographic expression analysis of MHC-I was performed using whole tissue sections (n = 100). Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations, mismatch repair (MMR) protein expression, and CpG-island methylator phenotype (CIMP) were investigated. Our results demonstrated that membranous MHC-I expression is frequently down-regulated in the process of invasion. Maintained MHC-I at the invasion front strongly predicted low-grade tumor budding (P = 0.0004). Triple-positive MHC-I/CD8/TIA1 in the tumor microenvironment predicted early T-stage (P = 0.0031), absence of lymph node metastasis (P = 0.0348), lymphatic (P = 0.0119) and venous invasion (P = 0.006), and highly favorable 5-year survival (90.9% vs 39.3% in triple-negative patients; P = 0.0032). MHC-I loss was frequent in KRAS-mutated, CD8+ CRC (P = 0.0228). No relationship was observed with CIMP, MMR, or BRAF mutation. In conclusion, tumor buds may evade immune recognition through downregulation of membranous MHC-I. A combined profile of MHC-I/CD8/TIA1 improves the prognostic value of antitumoral effector cells and should be preferred to a single marker approach.

To eat or not to eat—relationship of lichen herbivory by snails with secondary compounds and field frequency of lichens

Aims The biochemical defense of lichens against herbivores and its relationship to lichen frequency are poorly understood. Therefore, we tested whether chemical compounds in lichens act as feeding defense or rather as stimulus for snail herbivory among lichens and whether experimental feeding by snails is related to lichen frequency in the field. Methods In a no-choice feeding experiment, we fed 24 lichen species to snails of two taxa from the Clausilidae and Enidae families and compared untreated lichens and lichens with compounds removed by acetone rinsing. Then, we related experimental lichen consumption with the frequency of lichen species among 158 forest plots in the field (Schwäbische Alb, Germany), where we had also sampled snail and lichen species. Important findings In five lichen species, snails preferred treated samples over untreated controls, indicating chemical feeding defense, and vice versa in two species, indicating chemical feeding stimulus. Interestingly, compared with less frequent lichen species, snails consumed more of untreated and less of treated samples of more frequent lichen species. Removing one outlier species resulted in the loss of a significant positive relationship when untreated samples were analyzed separately. However, the interaction between treatment and lichen frequency remained significant when excluding single species or including snail genus instead of taxa, indicating that our results were robust and that lumping the species to two taxa was justified. Our results imply lichen-feeding snails to prefer frequent lichens and avoid less frequent ones because of secondary compound recognition. This supports the idea that consumers adapt to the most abundant food source.

Yellow laser light generation by frequency doubling of the output from a master oscillator fiber power amplifier system

We present a power-scalable approach for yellow laser-light generation based on standard Ytterbium (Yb) doped fibers. To force the cavity to lase at 1154 nm, far above the gain-maximum, measures must be taken to fulfill lasing condition and to suppress competing amplified spontaneous emission (ASE) in the high-gain region. To prove the principle we built a fiber-laser cavity and a fiber-amplifier both at 1154 nm. In between cavity and amplifier we suppressed the ASE by 70 dB using a fiber Bragg grating (FBG) based filter. Finally we demonstrated efficient single pass frequency doubling to 577 nm with a periodically poled lithium niobate crystal (PPLN). With our linearly polarized 1154 nm master oscillator power fiber amplifier (MOFA) system we achieved slope efficiencies of more than 15 % inside the cavity and 24 % with the fiber-amplifier. The frequency doubling followed the predicted optimal efficiency achievable with a PPLN crystal. So far we generated 1.5 W at 1154nm and 90 mW at 577 nm. Our MOFA approach for generation of 1154 nm laser radiation is power-scalable by using multi-stage amplifiers and large mode-area fibers and is therefore very promising for building a high power yellow laser-light source of several tens of Watt.

Radiation dose in pneumatic reduction of ileo-colic intussusceptions--results from a single-institution study

BACKGROUND Air enema under fluoroscopy is a well-accepted procedure for the treatment of childhood intussusception. However, the reported radiation doses of pneumatic reduction with conventional fluoroscopy units have been high in decades past. OBJECTIVE To compare current radiation doses at our institution to past doses reported by others for fluoroscopic-guided pneumatic reduction of ileo-colic intussusception in children. MATERIALS AND METHODS Since 2007 radiologists and residents in our department who perform reduction of intussusceptions have received a radiation risk training. We retrospectively analyzed the data of 45 children (5 months-8 years) who underwent a total of 48 pneumatic reductions of ileo-colic intussusception between 2008 and 2012. We analyzed data for screening time and dose area product (DAP) and compared these data to those reported up to and including the year 2000. RESULTS Our mean screening time measured by the DAP-meter was 53.8 s (range 1-320 s, median 33.0 s). The mean DAP was 11.4 cGy ∙ cm(2) (range 1-145 cGy ∙ cm(2), median 5.45 cGy ∙ cm(2)). There was one bowel perforation, in a 1-year-old boy requiring surgical revision. Only three studies in the literature presented radiation exposure results on children who received pneumatic or hydrostatic reduction of intussusception under fluoroscopy. Screening times and dose area products in those studies, which were published in the 1990 s and in the year 2000, were substantially higher than those in our sample. CONCLUSION Low-frequency pulsed fluoroscopy and other dose-saving keys as well as the radiation risk training might have helped to improve the quality of the procedure in terms of radiation exposure.

Frequency modulation of ERK activation dynamics rewires cell fate.

Transient versus sustained ERK MAP kinase (MAPK) activation dynamics induce proliferation versus differentiation in response to epidermal (EGF) or nerve (NGF) growth factors in PC-12 cells. Duration of ERK activation has therefore been proposed to specify cell fate decisions. Using a biosensor to measure ERK activation dynamics in single living cells reveals that sustained EGF/NGF application leads to a heterogeneous mix of transient and sustained ERK activation dynamics in distinct cells of the population, different than the population average. EGF biases toward transient, while NGF biases toward sustained ERK activation responses. In contrast, pulsed growth factor application can repeatedly and homogeneously trigger ERK activity transients across the cell population. These datasets enable mathematical modeling to reveal salient features inherent to the MAPK network. Ultimately, this predicts pulsed growth factor stimulation regimes that can bypass the typical feedback activation to rewire the system toward cell differentiation irrespective of growth factor identity.

THE MICROCELL-MEDIATED TRANSFER OF SINGLE HUMAN CHROMOSOMES INTO RECIPIENT MOUSE CELLS

Microcell-mediated chromosome transfer is a method of gene transfer which allows for the introduction of single or small groups of intact chromosomes into recipient host cells. Microcell transfer was first performed by Fournier and Ruddle using rodent microcells and various recipient cells. Expansion of this technology to include the transfer of normal human genetic material has been hindered because large micronucleate populations from diploid human cells have been unobtainable. This dissertation research describes, however, the methods for production of micronuclei in 40-60% of normal human fibroblasts. Once micronucleate cells were obtained, they were enucleated by centrifugation in the presence of Cytochalasin B; the microcells were then purified and fused to recipient mouse (LMTK('-)) cells using a new fusion protocol employing polyethylene glycol containing phytohemagglutinin. Microcell clones were isolated from the HAT selection system. Alkaline Giemsa staining performed on these hybrids indicated the presence of a single human chromosome in each of seven microcell clones from three separate experiments. That chromosome was further identified by G banding analysis to be human chromosome #17, which codes for thymidine kinase. The time course for production of these hybrids from fusion to karyotypic analysis was 6 weeks. The viability of the transferred human genetic material was assessed by electrophoretic isozyme analysis.^ Subsequent experiments were performed in an attempt to optimize the transfer frequency for the thymidine kinase gene using this system. Results indicated that the frequency could be increased from < 1 x 10('-6) in initial experiments to 2 x 10('-5) in the latest experiment. Analyses were also conducted to determine the number of chromosomes per isolated microcell as well as to investigate the stability of the transferred human chromosome in the mouse genome. ^

Dissolution rate spectra data of calcite single crystal and micrite material

The large discrepancy between field and laboratory measurements of mineral reaction rates is a long-standing problem in earth sciences, often attributed to factors extrinsic to the mineral itself. Nevertheless, differences in reaction rate are also observed within laboratory measurements, raising the possibility of intrinsic variations as well. Critical insight is available from analysis of the relationship between the reaction rate and its distribution over the mineral surface. This analysis recognizes the fundamental variance of the rate. The resulting anisotropic rate distributions are completely obscured by the common practice of surface area normalization. In a simple experiment using a single crystal and its polycrystalline counterpart, we demonstrate the sensitivity of dissolution rate to grain size, results that undermine the use of "classical" rate constants. Comparison of selected published crystal surface step retreat velocities (Jordan and Rammensee, 1998) as well as large single crystal dissolution data (Busenberg and Plummer, 1986) provide further evidence of this fundamental variability. Our key finding highlights the unsubstantiated use of a single-valued "mean" rate or rate constant as a function of environmental conditions. Reactivity predictions and long-term reservoir stability calculations based on laboratory measurements are thus not directly applicable to natural settings without a probabilistic approach. Such a probabilistic approach must incorporate both the variation of surface energy as a general range (intrinsic variation) as well as constraints to this variation owing to the heterogeneity of complex material (e.g., density of domain borders). We suggest the introduction of surface energy spectra (or the resulting rate spectra) containing information about the probability of existing rate ranges and the critical modes of surface energy.

Single-Stage Grid-Connected Forward Microinverter with Boundary Mode Control

This paper presents a microinverter to be integrated into a solar module. The proposed solution combines a forward converter and a constant off-time boundary mode control, providing MPPT capability and unity power factor in a single-stage converter. The transformer structure of the power stage remains as in the classical DC-DC forward converter. Transformer primary windings are utilized for power transfer or demagnetization depending on the grid semi-cycle. Furthermore, bidirectional switches are used on the secondary side allowing direct connection of the inverter to the grid. Design considerations for the proposed solution are provided, regarding the inductance value, transformer turns ratio and frequency variation during a line semi-cycle. The decoupling of the twice the line frequency power pulsation is also discussed, as well as the maximum power point tracking (MPPT) capability. Simulation and experimental results for a 100W prototype are enclosed

Bandlimited Airy Pulses for Invariant Propagation in Single-Mode Fibers

By spectral analysis, and using joint time-frequency representations, we present the theoretical basis to design invariant bandlimited Airy pulses with an arbitrary degree of robustness and an arbitrary range of single-mode fiber chromatic dispersion. The numerically simulated examples confirm the theoretically predicted pulse partial invariance in the propagation of the pulse in the fiber.

High-frequency signal generation using 1550 nm VCSEL subject to two-frequency optical injection

We experimentally investigate high-frequency microwave signal generation using a 1550 nm single-mode VCSEL subject to two-frequency optical injection. We first consider a situation in which the injected signals come from two similar VCSELs. The polarization of the injected light is parallel to that of the injected VCSEL. We obtain that the VCSEL can be locked to one of the injected signals, but the observed microwave signal is originated by beating at the photodetector. In a second situation we consider injected signals that come from two external cavity tunable lasers with a significant increase of the injected power with respect to the VCSEL-by-VCSEL injection case. The polarization of the injected light is orthogonal to that of the free-running slave VCSEL. We show that in this case it is possible to generate a microwave signal inside the VCSEL cavity. © (2013) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Microfabrication processes for microfluidic devices on a single laser Workstation: direct writing lithography on SU-8, laser ablation on polymers and mask manufacturing

We demonstrate the capability of a laser micromachining workstation for cost-effective manufacturing of a variety of microfluidic devices, including SU-8 microchannels on silicon wafers and 3D complex structures made on polyimide Kapton® or poly carbonate (PC). The workstation combines a KrF excimer laser at 248 nm and a Nd3+:YVO4 DPSS with a frequency tripled at 355 nm with a lens magnification 10X, both lasers working at a pulsed regime with nanoseconds (ns) pulse duration. Workstation also includes a high-resolution motorized XYZ-tilt axis (~ 1 um / axis) and a Through The Lens (TTL) imaging system for a high accurate positioning over a 120 x 120 mm working area. We have surveyed different fabrication techniques: direct writing lithography,mask manufacturing for contact lithography and polymer laser ablation for complex 3D devices, achieving width channels down to 13μ m on 50μ m SU-8 thickness using direct writing lithography, and width channels of 40 μm for polyimide on SiO2 plate. Finally, we have tested the use of some devices for capillary chips measuring the flow speed for liquids with different viscosities. As a result, we have characterized the presence of liquid in the channel by interferometric microscopy.

Processing of ultra-wideband low-frequency signals, for application in Foliage Penetration (FOPEN) Synthetic Aperture Radar (SAR) systems

Foliage Penetration (FOPEN) radar systems were introduced in 1960, and have been constantly improved by several organizations since that time. The use of Synthetic Aperture Radar (SAR) approaches for this application has important advantages, due to the need for high resolution in two dimensions. The design of this type of systems, however, includes some complications that are not present in standard SAR systems. FOPEN SAR systems need to operate with a low central frequency (VHF or UHF bands) in order to be able to penetrate the foliage. High bandwidth is also required to obtain high resolution. Due to the low central frequency, large integration angles are required during SAR image formation, and therefore the Range Migration Algorithm (RMA) is used. This project thesis identifies the three main complications that arise due to these requirements. First, a high fractional bandwidth makes narrowband propagation models no longer valid. Second, the VHF and UHF bands are used by many communications systems. The transmitted signal spectrum needs to be notched to avoid interfering them. Third, those communications systems cause Radio Frequency Interference (RFI) on the received signal. The thesis carries out a thorough analysis of the three problems, their degrading effects and possible solutions to compensate them. The UWB model is applied to the SAR signal, and the degradation induced by it is derived. The result is tested through simulation of both a single pulse stretch processor and the complete RMA image formation. Both methods show that the degradation is negligible, and therefore the UWB propagation effect does not need compensation. A technique is derived to design a notched transmitted signal. Then, its effect on the SAR image formation is evaluated analytically. It is shown that the stretch processor introduces a processing gain that reduces the degrading effects of the notches. The remaining degrading effect after processing gain is assessed through simulation, and an experimental graph of degradation as a function of percentage of nulled frequencies is obtained. The RFI is characterized and its effect on the SAR processor is derived. Once again, a processing gain is found to be introduced by the receiver. As the RFI power can be much higher than that of the desired signal, an algorithm is proposed to remove the RFI from the received signal before RMA processing. This algorithm is a modification of the Chirp Least Squares Algorithm (CLSA) explained in [4], which adapts it to deramped signals. The algorithm is derived analytically and then its performance is evaluated through simulation, showing that it is effective in removing the RFI and reducing the degradation caused by both RFI and notching. Finally, conclusions are drawn as to the importance of each one of the problems in SAR system design.