Frequency selectivity measured both psychophysically and physiologically

The ability to resolve the individual frequency components of a complex sound is known as frequency selectivity. The auditory system seems to act as a series of overlapping band-pass filters or auditory filters (AF), the width of which describe frequency selectivity. It is a fundamental and extensively studied property of the auditory system, yet its neural basis is not fully understood. This is due, in part, to the fact that two distinct approaches are taken to explore it; psychophysics and physiology, the results of which are difficult to reconcile. AF are measured in quite different ways in the two sub-fields. Psychophysics measures the ability of the system as a whole by using masking paradigms to measure the bandwidth of AF from behavioural data. A preferred method in human psychophysics is notched noise (NN) masking using forward masking with fixed signal level, since it does not suffer from confounds like suppression and off-frequency listening. In physiology bandwidth can be measured for single cells, or a population of cells, at various levels of the auditory system, and is traditionally done by observing the number of action potentials elicited in response to pure tone stimuli. The auditory system is known to be highly non-linear and so comparing the results of such vastly different approaches is problematic. Also, psychophysics measures the detection threshold of 'signal' sounds; how this compares to mean spike rates used in physiology is not clear. Attempts have been made in the past to apply the same method in animals to measure both psychophysical and physiological bandwidths, with varying degree of success. No successful attempt has been made to use an up-to-date method used in human psychophysics. In this thesis I take a step towards comparing psychophysical and physiological results by 1) developing a novel method that allows forward masked NN bandwidths to be measured behaviourally in the ferret, and 2) applying the same psychophysical paradigm to measuring bandwidth in guinea pig inferior colliculus (IC) and primary auditory cortex (A1) neurons. In addition a signal detection theory (SDT) approach is used on the physiological data to make results more comparable to psychophysical ones. Results from the behavioural method show that it can be used to successfully measure both forward and simultaneously masked NN bandwidths in the same animal, and that these measurements are in close agreement with one another and with bandwidths measured using previous methods. Results from the guinea pig physiology study show that bandwidths measured from IC neurons using the psychophysical NN paradigm are narrower than pure tone estimates of bandwidth, in the same neurons. However, the NN estimates are in close agreement with auditory peripheral and perceptual bandwidths, a finding which differs substantially from previous studies. Unexpectedly, however, bandwidths estimated from A1 neurons using masking show much finer tuning at high frequencies than seen further down the auditory system. This tuning is not only narrower than pure tone tuning in these neurons, but also finer than psychophysically measured estimates, which represent the auditory system as a whole. However, this may be related to the greater non-linearity of cortical neurons compared with those in the midbrain and lower. This work demonstrates that it is possible to reconcile different measurements of tuning in the auditory system by using appropriate methods. It also highlights the complex nature of auditory neurons and how care must be taken when measuring frequency selectivity using different approaches. In addition it provides a method for measuring auditory bandwidths psychophysically and physiologically in the same animal, allowing a direct comparison between the two; a vital step in investigating the neural basis of perceptual frequency selectivity

Frequency selectivity measured both psychophysically and physiologically

The ability to resolve the individual frequency components of a complex sound is known as frequency selectivity. The auditory system seems to act as a series of overlapping band-pass filters or auditory filters (AF), the width of which describe frequency selectivity. It is a fundamental and extensively studied property of the auditory system, yet its neural basis is not fully understood. This is due, in part, to the fact that two distinct approaches are taken to explore it; psychophysics and physiology, the results of which are difficult to reconcile. AF are measured in quite different ways in the two sub-fields. Psychophysics measures the ability of the system as a whole by using masking paradigms to measure the bandwidth of AF from behavioural data. A preferred method in human psychophysics is notched noise (NN) masking using forward masking with fixed signal level, since it does not suffer from confounds like suppression and off-frequency listening. In physiology bandwidth can be measured for single cells, or a population of cells, at various levels of the auditory system, and is traditionally done by observing the number of action potentials elicited in response to pure tone stimuli. The auditory system is known to be highly non-linear and so comparing the results of such vastly different approaches is problematic. Also, psychophysics measures the detection threshold of 'signal' sounds; how this compares to mean spike rates used in physiology is not clear. Attempts have been made in the past to apply the same method in animals to measure both psychophysical and physiological bandwidths, with varying degree of success. No successful attempt has been made to use an up-to-date method used in human psychophysics. In this thesis I take a step towards comparing psychophysical and physiological results by 1) developing a novel method that allows forward masked NN bandwidths to be measured behaviourally in the ferret, and 2) applying the same psychophysical paradigm to measuring bandwidth in guinea pig inferior colliculus (IC) and primary auditory cortex (A1) neurons. In addition a signal detection theory (SDT) approach is used on the physiological data to make results more comparable to psychophysical ones. Results from the behavioural method show that it can be used to successfully measure both forward and simultaneously masked NN bandwidths in the same animal, and that these measurements are in close agreement with one another and with bandwidths measured using previous methods. Results from the guinea pig physiology study show that bandwidths measured from IC neurons using the psychophysical NN paradigm are narrower than pure tone estimates of bandwidth, in the same neurons. However, the NN estimates are in close agreement with auditory peripheral and perceptual bandwidths, a finding which differs substantially from previous studies. Unexpectedly, however, bandwidths estimated from A1 neurons using masking show much finer tuning at high frequencies than seen further down the auditory system. This tuning is not only narrower than pure tone tuning in these neurons, but also finer than psychophysically measured estimates, which represent the auditory system as a whole. However, this may be related to the greater non-linearity of cortical neurons compared with those in the midbrain and lower. This work demonstrates that it is possible to reconcile different measurements of tuning in the auditory system by using appropriate methods. It also highlights the complex nature of auditory neurons and how care must be taken when measuring frequency selectivity using different approaches. In addition it provides a method for measuring auditory bandwidths psychophysically and physiologically in the same animal, allowing a direct comparison between the two; a vital step in investigating the neural basis of perceptual frequency selectivity

Biophysical modeling of a cochlear implant system: progress on closed-loop design using a novel patient-specific evaluation platform

The modern cochlear implant is one of the most successful neural stimulation devices, which partially mimics the workings of the auditory periphery. In the last few decades it has created a paradigm shift in hearing restoration of the deaf population, which has led to more than 324,000 cochlear implant users today. Despite its great success there is great disparity in patient outcomes without clear understanding of the aetiology of this variance in implant performance. Furthermore speech recognition in adverse conditions or music appreciation is still not attainable with today's commercial technology. This motivates the research for the next generation of cochlear implants that takes advantage of recent developments in electronics, neuroscience, nanotechnology, micro-mechanics, polymer chemistry and molecular biology to deliver high fidelity sound. The main difficulties in determining the root of the problem in the cases where the cochlear implant does not perform well are two fold: first there is not a clear paradigm on how the electrical stimulation is perceived as sound by the brain, and second there is limited understanding on the plasticity effects, or learning, of the brain in response to electrical stimulation. These significant knowledge limitations impede the design of novel cochlear implant technologies, as the technical specifications that can lead to better performing implants remain undefined. The motivation of the work presented in this thesis is to compare and contrast the cochlear implant neural stimulation with the operation of the physiological healthy auditory periphery up to the level of the auditory nerve. As such design of novel cochlear implant systems can become feasible by gaining insight on the question `how well does a specific cochlear implant system approximate the healthy auditory periphery?' circumventing the necessity of complete understanding of the brain's comprehension of patterned electrical stimulation delivered from a generic cochlear implant device. A computational model, termed Digital Cochlea Stimulation and Evaluation Tool (‘DiCoStET’) has been developed to provide an objective estimate of cochlear implant performance based on neuronal activation measures, such as vector strength and average activation. A patient-specific cochlea 3D geometry is generated using a model derived by a single anatomical measurement from a patient, using non-invasive high resolution computed tomography (HRCT), and anatomically invariant human metrics and relations. Human measurements of the neuron route within the inner ear enable an innervation pattern to be modelled which joins the space from the organ of Corti to the spiral ganglion subsequently descending into the auditory nerve bundle. An electrode is inserted in the cochlea at a depth that is determined by the user of the tool. The geometric relation between the stimulation sites on the electrode and the spiral ganglion are used to estimate an activating function that will be unique for the specific patient's cochlear shape and electrode placement. This `transfer function', so to speak, between electrode and spiral ganglion serves as a `digital patient' for validating novel cochlear implant systems. The novel computational tool is intended for use by bioengineers, surgeons, audiologists and neuroscientists alike. In addition to ‘DiCoStET’ a second computational model is presented in this thesis aiming at enhancing the understanding of the physiological mechanisms of hearing, specifically the workings of the auditory synapse. The purpose of this model is to provide insight on the sound encoding mechanisms of the synapse. A hypothetical mechanism is suggested in the release of neurotransmitter vesicles that permits the auditory synapse to encode temporal patterns of sound separately from sound intensity. DiCoStET was used to examine the performance of two different types of filters used for spectral analysis in the cochlear implant system, the Gammatone type filter and the Butterworth type filter. The model outputs suggest that the Gammatone type filter performs better than the Butterworth type filter. Furthermore two stimulation strategies, the Continuous Interleaved Stimulation (CIS) and Asynchronous Interleaved Stimulation (AIS) have been compared. The estimated neuronal stimulation spatiotemporal patterns for each strategy suggest that the overall stimulation pattern is not greatly affected by the temporal sequence change. However the finer detail of neuronal activation is different between the two strategies, and when compared to healthy neuronal activation patterns the conjecture is made that the sequential stimulation of CIS hinders the transmission of sound fine structure information to the brain. The effect of the two models developed is the feasibility of collaborative work emanating from various disciplines; especially electrical engineering, auditory physiology and neuroscience for the development of novel cochlear implant systems. This is achieved by using the concept of a `digital patient' whose artificial neuronal activation is compared to a healthy scenario in a computationally efficient manner to allow practical simulation times.Open Acces

Affective Computing

This book provides an overview of state of the art research in Affective Computing. It presents new ideas, original results and practical experiences in this increasingly important research field. The book consists of 23 chapters categorized into four sections. Since one of the most important means of human communication is facial expression, the first section of this book (Chapters 1 to 7) presents a research on synthesis and recognition of facial expressions. Given that we not only use the face but also body movements to express ourselves, in the second section (Chapters 8 to 11) we present a research on perception and generation of emotional expressions by using full-body motions. The third section of the book (Chapters 12 to 16) presents computational models on emotion, as well as findings from neuroscience research. In the last section of the book (Chapters 17 to 22) we present applications related to affective computing

Tracing the evolution of long non-coding RNAs: Principles of comparative transcriptomics for splice site conservation and biological applications

Eukaryotic cells exhibit an extensive transcriptional diversity. Only about a quarter of the total RNA in the human cell can be accounted for by messenger RNA (mRNA), which convey genetic code for protein generation. The remaining part of the transcriptome consists of rather heterogenous molecules. While some classes are well defined and have been shown to carry out distinct functions, ranging from housekeeping to complex regulatory tasks, a big fraction of the transcriptional output is categorized solely based on the lack of protein-coding capacity and transcript length. Several studies have shown, that as a group, mRNA-like long non-coding RNAs (lncRNAs), are under stabilizing selection, however at much weaker levels than mRNAs. The conservation at the level of primary sequence is even lower, blurring the contrast between exonic and intronics parts, which impedes traditional methods of genome-wide homology search. As a consequence their evolutionary history is a fairly unexplored field and apart from a few experimentally studied cases, the vast majority of them is reported to be poorly conserved. However, the pervasive transcription and the highly spatio-temporal specific expression patterns of lncRNAs suggests their functional importance and makes their evolutionary age and conservation patterns a topic of interest. By employing diverse computational methods, recent studies shed light on the common conservation of lncRNA’s secondary and gene structures, highlighting the significance of structural features on functionality. Splice sites, in particular, are frequently retained over very large evolutionary time scales, as they maintain the intron-exon-structure of the transcript. Consequently, the conservation of splice sites can be utilized in a comparative genomics approach to establish homology and predict evolutionarily well-conserved transcripts, regardless of their coding capacity. Since splice site conservation cannot be directly inferred from experimental evidence, in the course of this thesis a computational pipeline was established to generate comparative maps of splice sites based on multiple sequence alignments together with transcriptomics data. Scoring schemes for splice site motifs are employed to assess the conservation of orthologs. This resource can then be used to systemically study the conservation patterns of RNAs and their gene structures. This thesis will demonstrate the versatility of this method by showcasing biological applications of three distinct studies. First, a comprehensive annotation of the human transcriptome, from RefSeq, ESTs and GENCODE, was used to trace the evolution of human lncRNAs. A large majority of human lncRNAs is found to be conserved across Eutheria, and many hundreds originated before the divergence of marsupials and placental mammals. However, they exhibit a rapid turnover of their transcript structures, indicating that they are actual ancient components of the vertebrate genome with outstanding evolutionary plasticity. Additionally, a public web server was setup, which allows the user to retrieve sets of orthologous splice sites from pre-computed comparative splice site maps and inspect visualizations of their conservation in the respective species. Second, a more specific data set of non-colinearly spliced latimerian RNAs is studied to fathom the origins of atypical transcripts. RNA-seq data from two coelacanth species are analyzed, yielding thousands of circular and trans-spliced products, with a surprising exclusivity of the majority of their splice junctions to atypically spliced forms, that is they are not used in linear isoforms. The conservation analysis with comparative splice site maps yielded high conservation levels for both cir- cularizing and trans-connecting splice sites. This fact in combination with their abundance strongly suggests that atypical RNAs are evolutionarily old and of functional importance. Lastly, comparative splice site maps are used to investigate the role of lncRNAs in the evolution of the Alzheimer’s disease (AD). The human specificity of AD clearly points out a phylogenetic aspect of the disease, which makes the evolutionary analysis a very promising field of research. Protein- coding and non-protein-coding regions, that have been identified to be differentially expressed in AD patients, are analyzed for conservation of their splice site and evolution of their exon-intron-structure. Both non-coding and protein-coding AD-associated genes are shown to have evolved more rapidly in their gene structure than the genome at large. This supports the view of AD as a consequence of the recent rapid adaptive evolution of the human brain. This phylogenetic trait might have far reaching consequences with respect to the appropriateness of animal models and the development of disease-modifying strategies.Eukaryotische Zellen legen eine umfangreiche transkriptionelle Vielfalt an den Tag. Nur etwa ein Viertel der in der menschlichen Zelle enthaltenen RNA ist messenger RNA (mRNA), welche den genetischen Code für die Proteingenerierung übermittelt. Der verbleibende Anteil des Transkriptoms besteht aus eher heterogenen Molekülen. Während einigen wohldefinierten Klassen spezifische Funktionen zugeordnet werden können, welche von Zellhaushalt bis zu komplexen regulatorischen Aufgaben reichen, wird ein großer Teil der transkriptionellen Produktion ausschließlich auf Grundlage der fehlenden Kodierungskapazität und der Transkriptlänge kategorisiert. Einige Studien zeigten, dass mRNA-ähnliche lange nicht-kodierende RNA (lncRNA) als Gruppe unter stabilisierender Selektion stehen, wenn auch in einem weitaus geringeren Ausmaß als mRNAs. Die Konservierung auf Ebene der primären Sequenz ist sogar noch niedriger, wodurch der Kontrast zwischen exonischen und intronischen Elementen verschwimmt und Methoden der traditionellen Homologiesuche erschwert werden. Infolgedessen ist die evolutionäre Geschichte der lncRNAs ein recht unerforschtes Gebiet und abgesehen von ein paar vereinzelten Fallstudien wird die große Mehrheit als schwach konserviert vermeldet. Die tiefgreifende Transkription und die in Raum und Zeit hochspezifischen Expressionsmuster von lncRNA deuten jedoch auf deren funktionelle Bedeutung hin und machen ihr evolutionäres Alter und ihre Konservierungsmuster zu einem Thema von Interesse. Durch die Verwendung von computergestützten Methoden konnten jüngste Studien die verbreitete Konservierung von Sekundär- und Genstruktur von lncRNAs aufzeigen, was die Signifikanz von strukturellen Merkmalen in Bezug auf deren Funktionalität unterstreicht. Spleißstellen im besonderen werden oft über lange evolutionäre Zeitspannen erhalten, da sie die Intron-Exon-Struktur des Transkripts bewahren. Folglich, kann die Konservierung von Spleißstellen durch einen Ansatz der vergleichenden Genomik benutzt werden, um Homologie herzuleiten und evolutionär gut konservierte Transkripte unabhängig von deren Kodierungskapazität zu prognostizieren. Da es nicht möglich ist die Spleißstellenkonservierung direkt anhand von experimentellen Indikatoren abzulesen, wurde im Zuge dieser These eine computergestützte Methode entwickelt, welche, basierend auf multiplen Sequenzalignments und Transkriptomikdaten, “Vergleichskarten” von Spleißstellen erstellt. Ein Punktebewertungssystem für Spleißstellenmotive wird benutzt um die Konservierung der Orthologen zu beurteilen. Diese Resource kann anschließend verwendet werden um systematisch die Konservierungsmuster von RNAs und deren Genstrukturen zu untersuchen. Diese Arbeit wird die Vielseitigkeit dieser Methode demonstrieren, indem die biologische Anwendung in drei verschiedenen Studien präsentiert wird. Zuerst wird eine umfassende Annotation des menschlichen Transkriptoms, basierend auf RefSeq, EST und GENCODE, benutzt, um die Evolution von humanen lncRNAs nachzuvollziehen. Es konnte festgestellt werden, dass eine große Mehrheit der menschlichen lncRNAs innerhalb der Eutheria konserviert ist und mehrere hundert bereits vor der Auseinanderentwicklung von Beuteltieren und höheren Säugetieren entstanden. Dennoch zeigen sie eine rasante Veränderung in ihren Transkriptstrukturen, welche darauf hindeutet, dass sie tatsächlich alte Bestandteile von Vertebratengenomen mit bemerkenswerter evolutionärer Formbarkeit sind. Zusätzlich wurde ein öffentlicher Webserver aufgesetzt, der dem Nutzer ermöglicht Datensätze orthologer Spleißstellen aus vorgenerierten Vergleichskarten zu extrahieren und Visualisierungen der Konservierung in den jeweiligen Spezies zu betrachten. Als zweites wird ein spezifischerer Datensatz von nicht-linear gespleißten Latimeria-RNA untersucht um die Ursprünge untypischer Transkripte zu ergründen. Die Analyse der RNA-seq Daten zweier Exemplare des Quastenflossers ergab tausende zirkulärer und Transspleiß-Produkte, wobei die Mehrheit der Spleißverbindungen eine überraschende Exklusivität für untypisch gespleißte Formen aufzeigt, d.h. diese werden nicht für lineare Isoformen genutzt. Die Konservierungsanalyse mit Spleißstellen-Vergleichskarten ergibt hohe Konservierungsniveaus sowohl für zirkulärisierende als auch für trans-verbindende Spleißstellen. Diese Tatsache in Kombination mit ihrem häufigen Vorkommen, deutet stark darauf hin, dass untypische RNAs evolutionär alt und von funktioneller Bedeutung sind. Zuletzt werden Spleißstellen-Vergleichskarten benutzt um die Rolle von lncRNAs in der Evolution der Alzheimer-Krankheit (AK) zu untersuchen. Die Spezifität der AK auf den Menschen weist klar auf einen phylogenetischen Aspekt der Krankheit hin, was deren evolutionäre Analyse zu einem vielversprechenden Forschungsgebiet macht. Proteinkodierende und nicht-proteinkodierende Regionen, bei denen eine differentielle Expression in AK-Patienten erkannt wurde, werden auf die Konservierung ihrer Spleißstellen und Evolution ihrer Exon-Intron-Strukturen hin analysiert. Es kann nachgewiesen werden, dass sich die Genstruktur von sowohl nicht-kodierenden als auch von proteinkodierenden AK-assoziierten Genen schneller entwickelt als das Genom im Allgemeinen. Das unterstützt die Auffassung, dass AK die Folge einer kürzlichen rasanten adaptiven Evolution des menschlichen Gehirns ist. Diese phylogenetische Eigenschaft könnte weitreichende Konsequenzen in Bezug auf die Angemessenheit von Tiermodellen und die Entwicklung von krankheitsmodifizierenden Strategien haben

Dyslexia and dysgraphia in Greek in relation to normal development: cross-linguistic and longitudinal studies.

Studies on developmental dyslexia in transparent orthographies have established that children learning to read in such languages hardly experience difficulties in word reading accuracy and phonological awareness tasks, but suffer from a reading speed deficit. On the other hand in the English orthography, where the mappings between graphemes and phonemes are largely inconsistent, children exhibit significant difficulties in both word reading accuracy and speed. Greek is characterized by a high degree of regularity for reading, but is inconsistent for spelling. The variability of phoneme-to-grapheme correspondences and the highly inflectional nature of the particular orthography constitute spelling in Greek a considerably demanding task. The present thesis comprises three studies that were concerned with understanding the reading and spelling difficulties that Greek children/participants with dyslexia have and their underlying cognitive deficits, in relation to typically developing children and English children/participants with dyslexia. The first study examined the reading and spelling difficulties in Greek- and English-speaking children/participants with dyslexia, each compared with two control groups. Greek children/participants with dyslexia outperformed their English counterparts on word/nonword phoneme deletion, word/nonword reading, and grammatical spelling. However the two language groups performed similarly on rapid digit naming, spoonerisms and on the choice tasks. Results are discussed in relation to the differences in orthographic consistency between the two languages. The second study examined the development of literacy skills in twenty-three Greek children/participants with dyslexia over a period of 18 months (10 years 5 months to 12 years 3 months). At Time 1 children/participants with dyslexia performed worse on literacy tests than chronological-age control children, but similarly to reading-age controls. At Time 2 children/participants with dyslexia performed worse on all the tasks than CA control children, and worse than RA controls on the tasks of phoneme deletion of nonwords, nonword reading and orthographic spelling. Moreover the concurrent and longitudinal predictors of children's/participants' with dyslexia and typically developing children's reading and spelling abilities were examined. The findings are discussed in relation to theories of normal and atypical reading and spelling development. The third study investigated the ability of twenty-three 10-13 year-old Greek children/participants with dyslexia, and their reading-level and age-level-matched children to spell derivational and inflectional suffixes. Children/participants with dyslexia performed significantly worse than CA controls and RA controls. When they spelled the inflectional ending of adjectives and nouns children/participants with dyslexia did not differ from RA controls. It is suggested that children/participants with dyslexia have weaknesses in grasping the morphological rules of the Greek orthographic system and applying this knowledge in the spelling of word suffixes. The thesis concludes with a discussion of findings in relation to previous literature, the limitations of the present studies and avenues for future research

CORPORATE SOCIAL RESPONSIBILITY IN ROMANIA

The purpose of this paper is to identify the main opportunities and limitations of corporate social responsibility (CSR). The survey was defined with the aim to involve the highest possible number of relevant CSR topics and give the issue a more wholesome perspective. It provides a basis for further comprehension and deeper analyses of specific CSR areas. The conditions determining the success of CSR in Romania have been defined in the paper on the basis of the previously cumulative knowledge as well as the results of various researches. This paper provides knowledge which may be useful in the programs promoting CSR.Corporate social responsibility, Supportive policies, Romania

2004 NASA Seal/Secondary Air System Workshop, Volume 1

The 2004 NASA Seal/Secondary Air System workshop covered the following topics: (1) Overview of NASA s new Exploration Initiative program aimed at exploring the Moon, Mars, and beyond; (2) Overview of the NASA-sponsored Ultra-Efficient Engine Technology (UEET) program; (3) Overview of NASA Glenn s seal program aimed at developing advanced seals for NASA s turbomachinery, space, and reentry vehicle needs; (4) Reviews of NASA prime contractor and university advanced sealing concepts including tip clearance control, test results, experimental facilities, and numerical predictions; and (5) Reviews of material development programs relevant to advanced seals development. The NASA UEET overview illustrated for the reader the importance of advanced technologies, including seals, in meeting future turbine engine system efficiency and emission goals. For example, the NASA UEET program goals include an 8- to 15-percent reduction in fuel burn, a 15-percent reduction in CO2, a 70-percent reduction in NOx, CO, and unburned hydrocarbons, and a 30-dB noise reduction relative to program baselines. The workshop also covered several programs NASA is funding to develop technologies for the Exploration Initiative and advanced reusable space vehicle technologies. NASA plans on developing an advanced docking and berthing system that would permit any vehicle to dock to any on-orbit station or vehicle, as part of NASA s new Exploration Initiative. Plans to develop the necessary mechanism and androgynous seal technologies were reviewed. Seal challenges posed by reusable re-entry space vehicles include high-temperature operation, resiliency at temperature to accommodate gap changes during operation, and durability to meet mission requirements