MEG/EEG source reconstruction, statistical evaluation, and visualization with NUTMEG.

NUTMEG is a source analysis toolbox geared towards cognitive neuroscience researchers using MEG and EEG, including intracranial recordings. Evoked and unaveraged data can be imported to the toolbox for source analysis in either the time or time-frequency domains. NUTMEG offers several variants of adaptive beamformers, probabilistic reconstruction algorithms, as well as minimum-norm techniques to generate functional maps of spatiotemporal neural source activity. Lead fields can be calculated from single and overlapping sphere head models or imported from other software. Group averages and statistics can be calculated as well. In addition to data analysis tools, NUTMEG provides a unique and intuitive graphical interface for visualization of results. Source analyses can be superimposed onto a structural MRI or headshape to provide a convenient visual correspondence to anatomy. These results can also be navigated interactively, with the spatial maps and source time series or spectrogram linked accordingly. Animations can be generated to view the evolution of neural activity over time. NUTMEG can also display brain renderings and perform spatial normalization of functional maps using SPM's engine. As a MATLAB package, the end user may easily link with other toolboxes or add customized functions

A new Karzanov-type O(n3) max-flow algorithm

A new algorithm is presented for finding maximal and maximum value flows in directed single commodity networks. The algorithm gradually converts a combination of blocking preflows and backflows to a maximal flow in the network. Unlike other maximal flow algorithms, the algorithm treats the network more symmetrically by attempting to increase flow on both the ForwardStep and the BackwardStep. The algorithm belongs to the so called phase algorithms, and is applied to Dinic-type layered networks. With an effort of at most O(n3) for maximum value flow, the algorithm ties with the fastest maximum flow algorithms in dense networks, where m [approximate] n2, and can therefore be seen as a significant alternate technique. The algorithm is based on the Karzanov [1] algorithm, and shares features with the algorithm of Tarjan [2]. The first version of this algorithm was presented by the author in [3].Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30217/1/0000609.pd

Spectroscopic investigation and quantitation of polymorphism and crystallinity of pharmaceutical compounds

Spectroscopy is increasingly used to investigate and monitor the solid state forms of pharmaceutical materials and products. Spectroscopy's speed, non-destructive sampling, compatibility with fibre optics and safety also make it attractive for in-line monitoring. In this thesis, the spectroscopic techniques Fourier transform Raman spectroscopy, terahertz pulsed spectroscopy and second harmonic generation were used to characterise and quantify polymorphism and crystallinity of pharmaceutical compounds. Where possible, the multivariate analysis technique partial least squares was used for quantitative analysis. Fourier transform Raman spectroscopy detects polarisability changes mainly associated with molecular vibrations. Terahertz pulsed spectroscopy is a new spectroscopic technique that operates between the infrared and microwave regions of the electromagnetic spectrum and detects dipole moment changes mainly associated with crystalline phonon vibrations in the solid state. Second harmonic generation is a nonlinear optical phenomenon that depends on the dipole moment in crystals and crystal symmetry. Several materials capable of existing in different solid state forms were used. FT-Raman spectroscopy was able to differentiate carbamazepine forms I and III, enalapril maleate forms I and II and y-crystalline and amorphous indomethacin. Combined with partial least squares the technique could quantify binary mixtures of CBZ forms I and III with a limit of detection as low as 1 %, and mixtures of enalapril maleate with a limit of detection of as low as 2%. Terahertz pulsed spectroscopy obtained very different spectra for carbamazepine forms I and III, enalapril maleate forms I and II, y-crystalline and amorphous indomethacin, crystalline and supercooled thermotropic liquid crystalline fenoprofen calcium, three forms of lactose, and five forms of sulphathiazole. At present the modes in the spectra cannot be attributed to specific phonon modes. Quantitation of binary mixtures of different forms of a compound using partial least squares analysis usually resulted in a limit of detection of about 1 %. Second harmonic generation was used to quantify binary mixtures of different forms of enalapril maleate and lactose, as well as binary mixtures of enalapril maleate form II and polyvinylpyrrolidone. A quantitative relationship was present for each of the mixtures, however the limits of detection were usually above 10%. The high value is probably due to the machine being a prototype and univariate analysis associated with a single output variable. Future improvements to the apparatus and measurement parameters are likely to reduce the limits of detection. Ranitidine hydrochloride polymorphs could also be differentiated using second harmonic generation, however y-crystalline and amorphous indomethacin and forms I and III of carbamazepine could not. The methods used in this thesis were successfully used for qualitative and quantitative analysis of polymorphism and crystallinity of pharmaceutical compounds. TPS and SHG are useful additions to the range of experimental techniques that can be used to investigate and monitor properties of pharmaceutical solids

Um estudo do algoritmo de Goldberg e Tarjan para o problema de luxo maximo

Orientador: Clovis Perin FilhoDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Matematica, Estatistica e Computação CientíficaResumo: Este trabalho consiste no estudo e na implementação do algoritmo de Goldberg e Tarjan para o problema' do fluxo máximo. Este algoritmo tem destacada importância por apresentar uma das complexidades mais baixas e também pelo fato de abordar o problema de maneira diferenciada. Goldberg e Tarjan utilizam a estrutura de dados árvores dinâmicas para atingir a complexidade O(nm log(n2/m)) numa rede n-nós, m-arcos. Em redes densas (m = O (n2)) a complexidade deste algoritmo é tão boa quanto qualquer outro algoritmo, tendo uma das melhores complexidades em redes de densidade moderada. (m = O(n3/2)). Este algoritmo apresenta duas versões, uma que não utiliza a estrutura de dados árvores dinâmicas e tem complexidade O(n3), e outra versão que incorpora ao algoritmo anterior as árvores dinâmicas, conseguindo a complexidade de O(nm log(n2 1m)). Foram realizados testes comparativos com as duas versões e os principais al&oritmos conhecidos para o problema, tendo em vista o tempo de CPU em cada método. As redes utilizadas neste trabalho têm características particulares.Abstract: Not informed.MestradoMestre em Matemática Aplicad

Semiannual progress report no. 1, 16 November 1964 - 30 June 1965

Summary reports of research in bioelectronics, electron streams and interactions, plasmas, quantum and optical electronics, radiation and propagation, and solid-state electronic

Studying connectivity in the neonatal EEG

In humans the few months surrounding birth comprise a developmentally critical period characterised by the growth of major neuronal networks as well as their initial tuning towards more functionally mature large-scale constellations. Proper wiring in the neonatal brain, especially during the last trimester of pregnancy and the first weeks of postnatal life, relies on the brain’s endogenous activity and remains critical throughout one’s life. Structural or functional abnormalities at the stage of early network formation may result in a neurological disorder later during maturation. Functional connectivity measures based on an infant electroencephalographic (EEG) time series may be used to monitor these processes. A neonatal EEG is temporally discrete and consists of events (e.g., spontaneous activity transients (SATs)) and the intervals between them (inter-SATs). During early maturation, communication between areas of the brain may be transmitted through two distinct mechanisms: synchronisation between neuronal oscillations and event co-occurrences. In this study, we proposed a novel algorithm capable of assessing the coupling on both of these levels. Our analysis of real data from preterm neonates using the proposed algorithm demonstrated its ability to effectively detect functional connectivity disruptions caused by brain lesions. Our results also suggest that SAT synchronisation represents the dominant means through which inter-areal cooperation occurs in an immature brain. Structural disturbances of the neuronal pathways in the brain carry a frequency selective effect on the functional connectivity decreasing at the event level. Next, we used mathematical models and computational simulations combined with real EEG data to analyse the propagation of electrical neuronal activity within the neonatal head. Our results show that the conductivity of the neonatal skull is much higher than that found in adults. This leads to greater focal spread of cortical signals towards the scalp and requires high-density electrode meshes for quality monitoring of neonatal brain activity. Additionally, we show that the specific structure of the neonatal skull fontanel does not represent a special pathway for the spread of electrical activity because of the overall high conductivity of the skull. Finally, we demonstrated that the choice of EEG recording montage may strongly affect the fidelity of non-redundant neuronal information registration as well as the output of functional connectivity analysis. Our simulations suggest that high-density EEG electrode arrays combined with mathematical transformations, such as the global average or current source density (CSD), provide more spatially accurate details about the underlying cortical activity and may yield results more robust against volume conduction effects. Furthermore, we provide clear instruction regarding how to optimise recording montages for different numbers of sensors.Lähikuukaudet ennen ja jälkeen syntymää ovat ihmisillä hermoston kehityksen kannalta kriittisiä vaiheita, joita luonnehtii mittavien hermostollisten verkostojen kasvu sekä niiden alustava virittäytyminen toiminnallisesti kypsiksi suuren mittakaavan yhteenliittymiksi. Vastasyntyneen aivojen koko loppuelämään vaikuttavien hermoverkostojen muodostuminen määräytyy ensimmäisten syntymän jälkeisten viikkojen mutta erityisesti raskauden viimeisen kolmanneksen aikaisen aivojen sisäsyntyisen aktiivisuuden mukaan. Rakenteelliset tai toiminnalliset epämuodostumat näiden varhaisten hermoverkostojen muodostumisvaiheessa voi johtaa neurologisiin häiriöihin myöhemmässä kypsymisessä. Varhaisen kehityksen vaiheita voidaan valvoa vastasyntyneillä mittaamalla hermoyhteyksien toiminnallista liittyvyyttä aivosähkökäyrien (EEG) aikasarjojen avuilla. Vastasyntyneen aivosähkökäyrä on ajallisesti epäjatkuva ja koostuu lyhytkestoisista spontaanin aktiivisuuden tapahtumista, SATeista (Spontaneous Activity Transients) sekä niiden välisistä ajanhetkistä, inter-SATeista. Varhaisessa hermostollisessa kypsymisessä aivoalueiden välinen yhteydenpito voi tapahtua kahdella eri mekanismilla: hermostollisten oskillaatioiden välisellä synkronisaatioilla ja tapahtumien samanaikaisuudella. Tässä tutkimuksessa me kehitimme uuden matemaattisen mallin, algoritmin, jolla voi arvioida näiden kahden mekanismin välistä kytkeytymistä. Vastasyntyneiden keskosten mittausdataan pohjautuva analyysimme osoitti, että kehittämämme algoritmi on toimiva väline aivovaurioiden aiheuttamien toiminnallisten liittyvyyskatkoksien havaitsemisessa. Tuloksemme osoittavat myös, että SAT-synkronisaatio on aivoalueiden pääasiallisin yhteydenpitokeino kypsymättömissä vastasyntyneen aivoissa. Hermostollisten yhteyksien rakenteelliset epämuodostumat heikentävät toiminnallista liittyvyyttä taajuuskohtaisesti tapahtumatasolla. Seuraavaksi me käytimme matemaattisia malleja ja tietokonesimulaatioita yhdistettynä varsinaiseen EEG-mittausdataan analysoidaksemme sähköisen hermostollisen aktiivisuuden leviämistä vastasyntyneen päässä. Tulostemme mukaan vastasyntyneen kallon sähkönjohtavuus on paljon korkeampi kuin aikuisilla ihmisillä. Tämä aiheuttaa aivokuoren signaalien suurempaa paikallista leviämistä päänahkaa kohti, minkä takia vastasyntyneen aivoaktiivisuuden luotettava rekisteröinti vaatii enemmän ja tiheämmin mittauselektrodeja kuin aikuisilla. Lisäksi todistimme, että vastasyntyneen kallon aukileet eivät muodosta erityistä reittiä sähköisen aktiivisuuden leviämiselle, kallon suuren johtavuuden takia. Lopuksi osoitimme, että EEG-mittausasetelman valinta voi vahvasti vaikuttaa ei-päällekkäisen hermostollisen datan mittaustarkkuuteen ja sitä seuraaviin liittyvyysanalyyseihin. Simulaatiomme mukaan suuritiheyksinen EEG-mittauselektrodiasetelma yhdistettynä matemaattisiin muunnoksiin, kuten virtalähdetiheyden (Current Source Density) globaalikeskiarvoon, tarjoavat spatiaalisesti tarkkoja yksityiskohtia alla sijaitsevasta aivokuoren aktiivisuudesta ja voi erottaa selkeästi sekundääristen virtatihentymien osuuden. Lisäksi laadimme selkeät ohjeet kuinka optimoida mittausasetelma eri elektrodimäärille

Modeling biophysical and neural circuit bases for core cognitive abilities evident in neuroimaging patterns: hippocampal mismatch, mismatch negativity, repetition positivity, and alpha suppression of distractors

This dissertation develops computational models to address outstanding problems in the domain of expectation-related cognitive processes and their neuroimaging markers in functional MRI or EEG. The new models reveal a way to unite diverse phenomena within a common framework focused on dynamic neural encoding shifts, which can arise from robust interactive effects of M-currents and chloride currents in pyramidal neurons. By specifying efficient, biologically realistic circuits that achieve predictive coding (e.g., Friston, 2005), these models bridge among neuronal biophysics, systems neuroscience, and theories of cognition. Chapter one surveys data types and neural processes to be examined, and outlines the Dynamically Labeled Predictive Coding (DLPC) framework developed during the research. Chapter two models hippocampal prediction and mismatch, using the DLPC framework. Chapter three presents extensions to the model that allow its application for modeling neocortical EEG genesis. Simulations of this extended model illustrate how dynamic encoding shifts can produce Mismatch Negativity (MMN) phenomena, including pharmacological effects on MMN reported for humans or animals. Chapters four and five describe new modeling studies of possible neural bases for alpha-induced information suppression, a phenomenon associated with active ignoring of stimuli. Two models explore the hypothesis that in simple rate-based circuits, information suppression might be a robust effect of neural saturation states arising near peaks of resonant alpha oscillations. A new proposal is also introduced for how the basal ganglia may control onset and offset of alpha-induced information suppression. Although these rate models could reproduce many experimental findings, they fell short of reproducing a key electrophysiological finding: phase-dependent reduction in spiking activity correlated with power in the alpha frequency band. Therefore, chapter five also specifies how a DLPC model, adapted from the neocortical model developed in chapter three, can provide an expectation-based model of alpha-induced information suppression that exhibits phase-dependent spike reduction during alpha-band oscillations. The model thus can explain experimental findings that were not reproduced by the rate models. The final chapter summarizes main theses, results, and basic research implications, then suggests future directions, including expanded models of neocortical mismatch, applications to artificial neural networks, and the introduction of reward circuitry

Ionic liquids as solvents for rare-earth metals: a combined XAS and Molecular Dynamics study

In this work a detailed investigation of the structural organization of ILs, both monocationic and dicationic, and their water mixtures has been carried out by combining XAS spectroscopy and Classical MD simulations. The same joint XAS-MD approach has been also applied to the study of the solvation properties of Ln(III) salts dissolved in ILs. The original application of EXAFS and MD simulations paves the route for the systematic use of an integrated approach, with increased reliability, in the structural investigation of ILs. All together these issues are expected to be of great help in the systematic design of IL systems to meet the requirements of key applications

Tracing physicochemical and structural changes in drug delivery systems and human cells by confocal Raman microscopy

The advances in drug delivery research regarding formulation strategies and technologies, and at the same time high regulatory demands for novel therapeutics, in turn require advanced analytical methods for their investigation. In this work, confocal Raman microscopy is successfully applied as a label-free, chemically selective and non-destructive method for in-depth analysis to gain insight into complex drug carrier systems, to understand cellular and non-cellular barriers in the human body, as well as to visualize drug and carrier uptake. The studies include examination of pellets and tablets, designed for controlled drug release, elucidation of mass transport mechanisms and in situ drug recrystallization upon drug release. Furthermore, the polymer distribution within bio-inspired polymeric fiber mats was visualized and successfully correlated to interactions of the fibers with human cells. Moreover, confocal Raman microscopy was used for investigation of human airway mucus microstructure, and for tracing molecular and structural changes upon chemical mucolysis. Further, the alveolar surfactant, was examined upon differentiation of primary epithelial lung cells utilizing both, linear and coherent Raman techniques. Finally, particle uptake into cells with different membrane properties was investigated by label-free intracellular trafficking of bioinspired therapeutics for targeted drug delivery. Altogether, this newly gained knowledge will help further advancement in drug delivery research beyond the current state-of-the-art.Die Fortschritte in der Entwicklung von Wirkstofftransporter-Systemen, insbesondere bezüglich neuerer Formulierungsstrategien und -technologien, und die hohen regulatorischen Anforderungen für neue Therapeutika erfordern hochentwickelte analytische Methoden für deren Untersuchungen. Im Rahmen dieser Arbeit wurde konfokale Raman Mikroskopie erfolgreich als eine markierungsfreie, chemisch selektive und nicht-destruktive Methode für eine detaillierte Analyse verwendet, um einen Einblick in komplexe Wirkstoffträgersysteme zu gewinnen, zelluläre und nicht-zelluläre menschliche Barrieren im menschlichen Körper zu verstehen, sowie Arzneistoffe und Partikel zu visualisieren. Die Studien umfassen Untersuchungen von Pellets und Tabletten für die kontrollierte Wirkstofffreigabe, erklären den Massentransportmechanismus und die in situ Wirkstoffrekristallisation nach Wirkstofffreisetzung. Darüber hinaus konnte die Polymerverteilungen innerhalb bio-inspirierter, elektrogesponnener Vliese visualisiert und deren Interaktion mit den menschlichen Zellen korreliert werden. Außerdem konnte die konfokale Raman-Mikroskopie für die Untersuchung der Mikrostruktur von Mukus aus den humanen Atemwegen und zur Verfolgung molekularer und struktureller Veränderungen nach chemischer Mukolyse eingesetzt werden. Mit Hilfe linearer und kohärenter Ramantechniken konnte zudem das alveolare Surfactant während der Differenzierung primärer epithelialer Lungenzellen untersucht werden. Letztlich wurde die Aufnahme von Partikeln in Zellen mit unterschiedlichen Membraneigenschaften mittels markierungsfreier, intrazellulärer Nachverfolgung von bio-inspirierten Therapeutika für die zielgerichtete Arzneistoffapplikation analysiert. Das hier neugewonnene Wissen erlaubt somit weitere Fortschritte in der Forschung des Wirkstofftransports jenseits des aktuellen Wissensstandes

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 337)

This bibliography lists 400 reports, articles and other documents introduced into the NASA Scientific and Technical Information System during May 1990. Subject coverage includes: aerospace medicine and psychology, life support systems and controlled environments, safety equipment, exobiology and extraterrestrial life, and flight crew behavior and performance