Development of a passive MEG stimulus for measurement of the binaural masking level difference

The ability to hear a target signal over background noise is an important aspect of efficient hearing in everyday situations. This mechanism depends on binaural hearing whenever there are differences in the inter-aural timing of inputs from the noise and the signal. Impairments in binaural hearing may underlie some auditory processing disorders, for example temporal-lobe epilepsies. The binaural masking level difference (BMLD) measures the advantage in detecting a tone whose inter-aural phase differs from that of the masking noise. BMLD’s are typically estimated psychophysically, but this is challenging in children or those with cognitive impairments. The aim of this doctorate is to design a passive measure of BMLD using magnetoencephalography (MEG) and test this in adults, children and patients with different types of epilepsy. The stimulus consists of Gaussian background noise with 500-Hz tones presented binaurally either in-phase or 180° out-of-phase between the ears. Source modelling provides the N1m amplitude for the in-phase and out-of-phase tones, representing the extent of signal perception over background noise. The passive BMLD stimulus is successfully used as a measure of binaural hearing capabilities in participants who would otherwise be unable to undertake a psychophysical task.

Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation

Carbon monoxide (CO) is a gaseous autacoid known to positively regulate vascular tone; however, its role in angiogenesis is unknown. The aim of this study was to investigate the effect of CO on angiogenesis and vascular endothelial growth factor (VEGF) receptor-2 phosphorylation. Human umbilical vein endothelial cells (HUVECs) were cultured on growth factor- reduced Matrigel and treated with a CO-releasing molecule (CORM-2) or exposed to CO gas (250 ppm). Here, we report the surprising finding that exposure to CO inhibits vascular endothelial growth factor (VEGF)-induced endothelial cell actin reorganisation, cell proliferation, migration and capillary-like tube formation. Similarly, CO suppressed VEGF-mediated phosphorylation of VEGFR-2 at tyrosine residue 1175 and 1214 and basic fibroblast growth factor- (FGF-2) and VEGF-mediated Akt phosphorylation. Consistent with these data, mice exposed to 250 ppm CO (1h/day for 14 days) exhibited a marked decrease in FGF-2-induced Matrigel plug angiogenesis (p<0.05). These data establish a new biological function for CO in angiogenesis and point to a potential therapeutic use for CO as an anti-angiogenic agent in tumour suppression.

The Romanian Orthodox Church

At first glance, the nationalist ideology of the French Revolution seems to have had little impact on the Orthodox Church in Romanian-speaking territories. Romanians were the predominant inhabitants of the principalities of Wallachia and Moldavia and the neighboring territories of Transylvania (including Crişana, Maramureş and Banat), Bukovina, Bessarabia, and Dobrudja. The majority of ethnic Romanians belonged to the Orthodox faith while their communities were at the intersection of geopo liti cal interests of the Rus sian, Ottoman, and Habsburg empires. In 1859 the Principalities of Wallachia and Moldavia (known as the Old Kingdom between 1866 and 1918) united into a single state under the rule of a local prince. The term "Romania" began to be used by the new state in its of cial documents in 1862. Two years later, the state supported the declaration of a Romanian autocephalous (in de pen dent) church that was recognized by the Ecumenical Patriarchate in 1885. As an integrative part of the Orthodox commonwealth, the church was situated between the competing jurisdictions of the Ecumenical Patriarchate and the Rus sian Orthodox Church, while its declaration of autocephaly followed a pattern in the spread of national churches in Southeastern Europe. From the Treaty of Kuchuk Kainardji of 1774 to the beginning of the Greek War for In de pen dence in 1821, the Romanian principalities were under the suzerainty of the Ottoman Empire, which had full control of their po liti cal and economic affairs. The sultan appointed princes, and the Porte determined their po liti cal and judicial status. The princes were drawn from the "Phanariots," and were directly appointed by the Porte from preponderantly Greek elite rather than the Romanian local elite, the boyars (boieri).1 In each principality, the church was headed by a metropolitan who was under the direct jurisdiction of the Ecumenical Patriarchate. That religion mattered to local population as a means of social cohesion was suggestively depicted by Anatole de Demidoff, an En glish traveler in the region in 1837. Arriving in Bucharest, the capital of Wallachia, he claimed that: I know of no city in Europe in which it is possible to find more agreeable society, or in which there is a better tone, united with the most charming gaiety⋯. Religion, which is here of the schismatic Greek creed, does not, properly speaking, hold any great empire over the minds of the Wallachian people, but they observe its outward forms, and particularly the austerities of fasting, with scrupulous exactitude. The people are seen to attend divine ser vice with every sign of respect, and the great number of churches existing in Wallachia, bear witness to the ardent zeal with which outward worship is honored.2 The Romanian Orthodox Church was a national institution, closely linked to social, economic, and po liti cal structures. In most cases, Orthodox hierarchs were appointed from the families of boyars, thus ensuring a close relationship with the state authorities and its policies. As one of the largest landowners in the principalities, the church had a prime role in administrating healthcare and education. Although the majority of the clergy was uneducated, it dispensed both ecclesiastical and civil justice and in many cases worked closely with boyars in local administration.3 The lower clergy not only contributed directly to the economy but also benefited from tax privileges. Some small villages had an unusually high proportion of clergy in comparison to the overall population. For example, in 1810, Stənisləveşti, a village in the south of Wallachia, was composed of eleven houses and had two priests, five deacons, and three cantors; similarly, the Frəsinet village of nineteen houses had two priests and five deacons.4 Although these cases were exceptional, they indicate both the economic value of being a member of the clergy and the wider canonical dimension of church jurisdiction. The special status of the clergy was reflected not only at lower but also at higher levels. Bishops and metropolitans engaged with state policy and in many cases opposition to the authorities led to the loss of a spiritual seat. The metropolitan of each principality worked with the prince and was president of the divan, the gathering of all boyars. He held the right to be the first person to comment on state policy and to make recommendations when the prince was absent. The metropolitan replaced the prince when the principality had no political ruler, such as in the cases of Metropolitan Veniamin Costachi of Moldavia in 1806 and Metropolitan Dositei Filitti of Wallachia, while the bishops of Buzəu and Argeş were members of the provisional government during the Rus sian occupation of the principalities in 1808. The higher clergy had both religious and political prerogatives in relation to foreign powers as evident in their heading of the boyars' delegation to peace negotiation between the Rus sian and Ottoman empires at Focşani in 1772 and addressing memoranda to the Austrian and Rus sian governments in 1802.5 The primary role of the church in the principalities of Moldavia and Wallachia was paralleled by the national mobilization of Orthodox communities in the neighboring territories that had Romanian inhabitants. Although throughout the region Orthodox communities were incorporated into church structures as part of the Habsburg, Austrian or Rus sian empires, the nineteenth century was characterized by the leadership's search for political autonomy and the building of a Romanian national identity. The Orthodox communities outside the Old Kingdom maintained relations with the faithful in principalities across the Carpathian Mountains and the Dniester River and sought support in their struggle for political and religious rights.

Digital Repository of Information and Knowledge - Fund “BellKnow”

The aim was to develop an archive containing detailed description of church bells. As an object of cultural heritage the bell has general properties such as geometric dimensions, weight, sound of each of the bells, the pitch of the tone as well as acoustical diagrams obtained using contemporary equipment. The audio, photo and video archive is developed by using advanced technologies for analysis, reservation and data protection.

Building OWL Ontology of Unique Bulgarian Bells Using Protégé Platform

We describe an ontological representation of data in an archive containing detailed description of church bells. As an object of cultural heritage the bell has general properties such as geometric dimensions, weight, sound of each of the bells, the pitch of the tone as well as acoustical diagrams obtained using contemporary equipment. We use Protégé platform in order to define basic ontological objects and relations between them.

Mathematical Modeling, Music Literacy and Their Transmission in Fine Arts Education

Report published in the Proceedings of the National Conference on "Education and Research in the Information Society", Plovdiv, May, 2014

Case study: auditory brain responses in a minimally verbal child with autism and cerebral palsy

An estimated 30% of individuals with autism spectrum disorders (ASD) remain minimally verbal into late childhood, but research on cognition and brain function in ASD focuses almost exclusively on those with good or only moderately impaired language. Here we present a case study investigating auditory processing of GM, a nonverbal child with ASD and cerebral palsy. At the age of 8 years, GM was tested using magnetoencephalography (MEG) whilst passively listening to speech sounds and complex tones. Where typically developing children and verbal autistic children all demonstrated similar brain responses to speech and nonspeech sounds, GM produced much stronger responses to nonspeech than speech, particularly in the 65–165 ms (M50/M100) time window post-stimulus onset. GM was retested aged 10 years using electroencephalography (EEG) whilst passively listening to pure tone stimuli. Consistent with her MEG response to complex tones, GM showed an unusually early and strong response to pure tones in her EEG responses. The consistency of the MEG and EEG data in this single case study demonstrate both the potential and the feasibility of these methods in the study of minimally verbal children with ASD. Further research is required to determine whether GM's atypical auditory responses are characteristic of other minimally verbal children with ASD or of other individuals with cerebral palsy.

Interictal autonomic abnormalities in idiopathic Rolandic Epilepsy

We investigated 50 young patients with a diagnosis of Rolandic Epilepsy (RE) for the presence of abnormalities in autonomic tone compared with 50 young patients with idiopathic generalized epilepsy with absences and 50 typically developing children of comparable age. We analyzed time domain (N-N interval, pNN50) and frequency domain (High Frequency (HF), Low Frequency (LF) and LF/HF ratio) indices from ten-minute resting EKG activity. Patients with RE showed significantly higher HF and lower LF power and lower LF/HF ratio than controls, independent of the epilepsy group, and did not show significant differences in any other autonomic index with respect to the two control groups. In RE, we found a negative relationship between both seizure load and frequency of sleep interictal EEG abnormalities with parasympathetic drive levels. These changes might be the expression of adaptive mechanisms to prevent the excessive sympathetic drive seen in patients with refractory epilepsies. © 2012 Elsevier Inc.

Revaloracion de la comedia de Pedro Munoz Seca: Un teatro menospreciado

The comedies of Pedro Muñoz Seca (1879-1936) received extraordinary public acclaim for over thirty years, yet critics rejected them. Although several experts have recently begun to study his plays in an objective manner, this author has generally either been underrated or omitted from theater histories. This study identifies the merit, contributions and relevance of Muñoz Seca's works so that the unwarranted void that now exists in Spanish theater annals is justly filled. Historical and biographical backgrounds and a brief sketch of the development of comedy in Spain serve to introduce the literary, political and social contexts in which the author develops the subgenre known as "astracán" and introduces the "fresco" character type. ^ This analysis illustrates Muñoz Seca's verbal comic techniques---the use of regional dialects and individuals' speech peculiarities, double entendres, incongruence, periphrasis, and ingenious plays on words. It also explores the author's profound theatrical sense manifested in inter-textual references and self-reflexivity within the content of his plays. In addition, it identifies the scenic creativity he displays through the use of cinematography, the removal of color from stage decor (or the elimination of scenery altogether), and the original application of music to create comic effect. Furthermore, this study comments the satirical tone projected in Muñoz Seca's characters' idiolect and barbarisms as socio-political conditions worsen. Finally, it brings forth the author's use of parody to criticize his society and to deride other theatrical genres in vogue during his time. ^ While the polarization between Muñoz Seca's popular success and the critics' rejection can be explained by esthetic and ideological prejudices, this dissertation ascertains that the true nature of the author's plays has not been properly identified. The "astracán" is a double parody; however, since it caricaturizes a comic subgenre that is already burlesque, its defining parodic features have been consistently misinterpreted as mere exaggerations and defects. What is more, as its critical content is not recognized, its renewing function goes unnoticed. Muñoz Seca's "astracán" illustrates an era of the Spanish comic stage and paves the way for the theater of the absurd. Its merit and relevance must be recognized. ^

An experimental and theoretical analysis of nitric oxide availability in the microcirculation

Nitric Oxide (NO) is produced in the vascular endothelium where it then diffuses to the adjacent smooth muscle cells (SMC) activating agents known to regulate vascular tone. The close proximity of the site of NO production to the red blood cells (RBC) and its known fast consumption by hemoglobin, suggests that the blood will scavenge most of the NO produced. Therefore, it is unclear how NO is able to play its role in accomplishing vasodilation. Investigation of NO production and consumption rates will allow insight into this paradox. DAF-FM is a sensitive NO fluorescence probe widely used for qualitative assessment of cellular NO production. With the aid of a mathematical model of NO/DAF-FM reaction kinetics, experimental studies were conducted to calibrate the fluorescence signal showing that the slope of fluorescent intensity is proportional to [NO]2 and exhibits a saturation dependence on [DAF-FM]. In addition, experimental data exhibited a Km dependence on [NO]. This finding was incorporated into the model elucidating NO 2 as the possible activating agent of DAF-FM. A calibration procedure was formed and applied to agonist stimulated cells, providing an estimated NO release rate of 0.418 ± 0.18 pmol/cm2s. To assess NO consumption by RBCs, measurements of the rate of NO consumption in a gas stream flowing on top of an RBC solution of specified Hematocrit (Hct) was performed. The consumption rate constant (kbl)in porcine RBCs at 25°C and 45% Hct was estimated to be 3500 + 700 s-1. kbl is highly dependent on Hct and can reach up to 9900 + 4000 s-1 for 60% Hct. The nonlinear dependence of kbl on Hct suggests a predominant role for extracellular diffusion in limiting NO uptake. Further simulations showed a linear relationship between varying NO production rates and NO availability in the SMCs utilizing the estimated NO consumption rate. The corresponding SMC [NO] level for the average NO production rate estimated was approximately 15.1 nM. With the aid of experimental and theoretical methods we were able to examine the NO paradox and exhibit that endothelial derived NO is able to escape scavenging by RBCs to diffuse to the SMCs.

Preservation of nitric oxide availability as nitrite and nitrosothiols

Nitric Oxide (NO) has been known for long to regulate vessel tone. However, the close proximity of the site of NO production to "sinks" of NO such as hemoglobin (Hb) in blood suggest that blood will scavenge most of the NO produced. Therefore, it is unclear how NO is able to play its physiological roles. The current study deals with means by which this could be understood. Towards studying the role of nitrosothiols and nitrite in preserving NO availability, a study of the kinetics of glutathione (GSH) nitrosation by NO donors in aerated buffered solutions was undertaken first. Results suggest an increase in the rate of the corresponding nitrosothiol (GSNO) formation with an increase in GSH with a half-maximum constant EC50 that depends on NO concentration, thus indicating a significant contribution of NO2 mediated nitrosation in the production of GSNO. Next, the ability of nitrite to be reduced to NO in the smooth muscle cells was evaluated. The NO formed was inhibited by sGC inhibitors and accelerated by activators and was independent of O2 concentration. Nitrite transport mechanisms and effects of exogenous nitrate on transport and reduction of nitrite were examined. The results showed that sGC can mediate nitrite reduction to NO and nitrite is transported across the smooth muscle cell membrane via anion channels, both of which can be attenuated by nitrate. Finally, a 2-D axisymmetric diffusion model was constructed to test the accumulation of NO in the smooth muscle layer from reduction of nitrite. It was observed that at the end of the simulation period with physiological concentrations of nitrite in the smooth muscle cells (SMC), a low sustained NO generated from nitrite reduction could maintain significant sGC activity and might affect vessel tone. The major nitrosating mechanism in the circulation at reduced O2 levels was found to be anaerobic and a Cu+ dependent GSNO reduction activity was found to deliver minor amounts of NO from physiological GSNO levels in the tissue.

Effect of arginine and oscillatory calcium ion (II) on vascular response mediated via nitric oxide signaling in normal and salt sensitive hypertensive rat mesenteric arterioles

Hypertension, a major risk factor in the cardiovascular system, is characterized by an increase in the arterial blood pressure. High dietary sodium is linked to multiple cardiovascular disorders including hypertension. Salt sensitivity, a measure of how the blood pressure responds to salt intake is observed in more than 50% of the hypertension cases. Nitric Oxide (NO), as an endogenous vasodilator serves many important biological roles in the cardiovascular physiology including blood pressure regulation. The physiological concentrations for NO bioactivity are reported to be in 0-500 nM range. Notably, the vascular response to NO is highly regulated within a small concentration spectrum. Hence, much uncertainty surrounds how NO modulates diverse signaling mechanisms to initiate vascular relaxation and alleviate hypertension. Regulating the availability of NO in the vasculature has demonstrated vasoprotective effects. In addition, modulating the NO release by different means has proved to restore endothelial function. In this study we addressed parameters that regulated NO release in the vasculature, in physiology and pathophysiology such as salt sensitive hypertension. We showed that, in the rat mesenteric arterioles, Ca2+ induced rapid relaxation (time constants 20.8 ± 2.2 sec) followed with a much slower constriction after subsequent removal of the stimulus (time constants 104.8 ± 10.0 sec). An interesting observation was that a fourfold increase in the Ca 2+ frequency improved the efficacy of arteriolar relaxation by 61.1%. Our results suggested that, Ca2+ frequency-dependent transient release of NO from the endothelium carried encoded information; which could be translated into different steady state vascular tone. Further, Agmatine, a metabolite of L-arginine, as a ligand, was observed to relax the mesenteric arterioles. These relaxations were NO-dependent and occurred via &agr;-2 receptor activity. The observed potency of agmatine (EC50, 138.7 ± 12.1 ± μM; n=22), was 40 fold higher than L-arginine itself (EC50, 18.3 ± 1.3 mM; n = 5). This suggested us to propose alternative parallel mechanism for L-arginine mediated vascular relaxation via arginine decarboxylase activity. In addition, the biomechanics of rat mesentery is important in regulation of vascular tone. We developed 2D finite element models that described the vascular mechanics of rat mesentery. With an inverse estimation approach, we identified the elasticity parameters characterizing alterations in normotensive and hypertensive Dahl rats. Our efforts were towards guiding current studies that optimized cardiovascular intervention and assisted in the development of new therapeutic strategies. These observations may have significant implications towards alternatives to present methods for NO delivery as a therapeutic target. Our work shall prove to be beneficial in assisting the delivery of NO in the vasculature thus minimizing the cardiovascular risk in handling abnormalities, such as hypertension.

La modernidad de los "Versos libres" de Jose Marti

The purpose of this dissertation is to analyze the collection of poems Versos libres written by José Martí, as a cycle of literary expression closely connected with the origins and development of the modernist movement, as well as to the emergence of what has been later termed the modernism of Hispanic-American literature. ^ The poetics of Versos libres is based on the liberating function attributed to them by their author, who was determined to reach with this cycle a level of expression where literary modernism and radical Americanism would be fully integrated, in order to enrich the communicative capabilities of poetic language, making it penetrate deep and complex realities: Man's conscience, psyche and creative effort, nature and history. ^ This study of the Versos libres as a cycle, allows us to characterize the contribution of such a work to Hispanic-American poetry as a result of a literary praxis whose tone makes Versos libres a piece of work that, in its best-realized moments, surpasses the limits of the turn-of-the-century Hispanic-American poetry; thus laying a bridge towards modern poetry in the Spanish language. ^ The dissertation is based on the direct and complete transcription of Martí's own handwritings of the Versos libres, included in his Poesía completa. Edición Crítica (1985), edited by Cintio Vitier, Fina García Marruz and the present author. ^

Theoretical Investigation of Intra- and Inter-cellular Spatiotemporal Calcium Patterns in Microcirculation

Microcirculatory vessels are lined by endothelial cells (ECs) which are surrounded by a single or multiple layer of smooth muscle cells (SMCs). Spontaneous and agonist induced spatiotemporal calcium (Ca2+) events are generated in ECs and SMCs, and regulated by complex bi-directional signaling between the two layers which ultimately determines the vessel tone. The contractile state of microcirculatory vessels is an important factor in the determination of vascular resistance, blood flow and blood pressure. This dissertation presents theoretical insights into some of the important and currently unresolved phenomena in microvascular tone regulation. Compartmental and continuum models of isolated EC and SMC, coupled EC-SMC and a multi-cellular vessel segment with deterministic and stochastic descriptions of the cellular components were developed, and the intra- and inter-cellular spatiotemporal Ca2+ mobilization was examined. Coupled EC-SMC model simulations captured the experimentally observed localized subcellular EC Ca2+ events arising from the opening of EC transient receptor vanilloid 4 (TRPV4) channels and inositol triphosphate receptors (IP3Rs). These localized EC Ca2+ events result in endothelium-derived hyperpolarization (EDH) and Nitric Oxide (NO) production which transmit to the adjacent SMCs to ultimately result in vasodilation. The model examined the effect of heterogeneous distribution of cellular components and channel gating kinetics in determination of the amplitude and spread of the Ca2+ events. The simulations suggested the necessity of co-localization of certain cellular components for modulation of EDH and NO responses. Isolated EC and SMC models captured intracellular Ca2+ wave like activity and predicted the necessity of non-uniform distribution of cellular components for the generation of Ca2+ waves. The simulations also suggested the role of membrane potential dynamics in regulating Ca2+ wave velocity. The multi-cellular vessel segment model examined the underlying mechanisms for the intercellular synchronization of spontaneous oscillatory Ca2+ waves in individual SMC. From local subcellular events to integrated macro-scale behavior at the vessel level, the developed multi-scale models captured basic features of vascular Ca2+ signaling and provide insights for their physiological relevance. The models provide a theoretical framework for assisting investigations on the regulation of vascular tone in health and disease.

The Road from Emmaus

THE ROAD FROM EMMAUS is a collection of 20 personal and lyric essays that explores the narrator’s role as mother and daughter through a close look at significant life events, including her parents’ divorce, a high-risk pregnancy, the death of her father, talking to her daughter for the first time about sex, and accompanying her daughter to the DMV for a learner’s permit. Through examining familial roles and relationships, the narrator’s longing for home emerges as a unifying theme. The essays in THE ROAD FROM EMMAUS vary in style and tone, from light and funny to serious and probing. The collection is divided into five sections, each highlighting a different aspect of the narrator’s life as she evolves from a child, to a young adult, a mother, and a daughter who must help take care of her aging parents.