A multivariable sampled-data model of an automobile driver

In this thesis, a multivariable system model of driver performance in the basic driving tasks is presented. The driver model described acts as a serial-process, priority-accessed, time-sharing computer. This model processes the input or output task which currently possesses the highest priority. Input tasks are represented by continuous signals sampled intermittently according to priority laws. Output tasks are modeled as simple analog processes operating on the last few intermittently generated output controls. An individual priority rule is constructed for each input and output task. The performance of the driver in the lateral control task involves a feedforward pattern which is consequence of the fact the driver looks several feet ahead of the pathway. A laboratory analysis of the feedforward aspects of the driver in the single-input single-output lateral control task is described --Abstract, page ii

Revan-degree indices on random graphs

Given a simple connected non-directed graph $G=(V(G),E(G))$, we consider two families of graph invariants: $RX_\Sigma(G) = \sum_{uv \in E(G)} F(r_u,r_v)$ (which has gained interest recently) and $RX_\Pi(G) = \prod_{uv \in E(G)} F(r_u,r_v)$ (that we introduce in this work); where $uv$ denotes the edge of $G$ connecting the vertices $u$ and $v$, $r_u$ is the Revan degree of the vertex $u$, and $F$ is a function of the Revan vertex degrees. Here, $r_u = \Delta + \delta - d_u$ with $\Delta$ and $\delta$ the maximum and minimum degrees among the vertices of $G$ and $d_u$ is the degree of the vertex $u$. Particularly, we apply both $RX_\Sigma(G)$ and R$X_\Pi(G)$ on two models of random graphs: Erd\"os-R\'enyi graphs and random geometric graphs. By a thorough computational study we show that \left and \left, normalized to the order of the graph, scale with the average Revan degree \left; here \left denotes the average over an ensemble of random graphs. Moreover, we provide analytical expressions for several graph invariants of both families in the dense graph limit.Comment: 16 pages, 10 figure

A database and digital signal processing framework for the perceptual analysis of voice quality

Bermúdez de Alvear RM, Corral J, Tardón LJ, Barbancho AM, Fernández Contreras E, Rando Márquez S, Martínez-Arquero AG, Barbancho I. A database and digital signal processing framework for the perceptual analysis of voice quality. Pan European Voice Conferenc: PEVOC 11 Abstract Book. Aug. 31-Sept.2, 2015.Introduction. Clinical assessment of dysphonia relies on perceptual as much as instrumental methods of analysis [1]. The perceptual auditory analysis is potentially subject to several internal and external sources of bias [2]. Furthermore acoustic analyses which have been used to objectively characterize pathological voices are likely to be affected by confusion variables such as the signal processing or the hardware and software specifications [3]. For these reasons the poor correlation between perceptual ratings and acoustic measures remains to be a controversial matter [4]. The availability of annotated databases of voice samples is therefore of main importance for clinical and research purposes. Databases to perform digital processing of the vocal signal are usually built from English speaking subjects’ sustained vowels [5]. However phonemes vary from one language to another and to the best of our knowledge there are no annotated databases with Spanish sustained vowels from healthy or dysphonic voices. This work shows our first steps to fill in this gap. For the aim of aiding clinicians and researchers in the perceptual assessment of voice quality a two-fold objective was attained. On the one hand a database of healthy and disordered Spanish voices was developed; on the other an automatic analysis scheme was accomplished on the basis of signal processing algorithms and supervised learning machine techniques. Material and methods. A preliminary annotated database was created with 119 recordings of the sustained Spanish /a/; they were perceptually labeled by three experienced experts in vocal quality analysis. It is freely available under Links in the ATIC website (www.atic.uma.es). Voice signals were recorded using a headset condenser cardioid microphone (AKG C-544 L) positioned at 5 cm from the speaker’s mouth commissure. Speakers were instructed to sustain the Spanish vowel /a/ for 4 seconds. The microphone was connected to a digital recorder Edirol R-09HR. Voice signals were digitized at 16 bits with 44100 Hz sampling rate. Afterwards the initial and last 0.5 second segments were cut and the 3 sec. mid portion was selected for acoustic analysis. Sennheiser HD219 headphones were used by judges to perceptually evaluate voice samples. To label these recordings raters used the Grade-Roughness-Breathiness (GRB) perceptual scale which is a modified version of the original Hirano’s GRBAS scale, posteriorly modified by Dejonckere et al., [6]. In order to improve intra- and inter-raters’ agreement two types of modifications were introduced in the rating procedure, i.e. the 0-3 points scale resolution was increased by adding subintervals to the standard 0-3 intervals, and judges were provided with a written protocol with explicit definitions about the subintervals boundaries. By this way judges could compensate for the potential instability that might occur in their internal representations due to the perceptual context influence [7]. Raters’ perceptual evaluations were simultaneously performed by means of connecting the Sennheiser HD219 headphones to a multi-channel headphone preamp Behringer HA4700 Powerplay Pro-XL. The Yin algorithm [8] was selected as initial front-end to identify voiced frames and extract their fundamental frequency. For the digital processing of voice signals some conventional acoustic parameters [6] were selected. To complete the analysis the Mel-Frequency Cepstral Coefficients (MFCC) were further calculated because they are based on the auditory model and they are thus closer to the auditory system response than conventional features. Results. In the perceptual evaluation excellent intra-raters agreement and very good inter-raters agreement were achieved. During the supervised machine learning stage some conventional features were found to attain unexpected low performance in the classification scheme selected. Mel Frequency Cepstral Coefficients were promising for assorting samples with normal or quasi-normal voice quality. Discussion and conclusions. Despite it is still small and unbalanced the present annotated data base of voice samples can provide a basis for the development of other databases and automatic classification tools. Other authors [9, 10, 11] also found that modeling the auditory non-linear response during signal processing can help develop objective measures that better correspond with perceptual data. However highly disordered voices classification remains to be a challenge for this set of features since they cannot be correctly assorted by either conventional variables or the auditory model based measures. Current results warrant further research in order to find out the usability of other types of voice samples and features for the automatic classification schemes. Different digital processing steps could be used to improve the classifiers performance. Additionally other types of classifiers could be taken into account in future studies. Acknowledgment. This work was funded by the Spanish Ministerio de Economía y Competitividad, Project No. TIN2013-47276-C6-2-R has been done in the Campus de Excelencia Internacional Andalucía Tech, Universidad de Málaga. References [1] Carding PN, Wilson JA, MacKenzie K, Deary IJ. Measuring voice outcomes: state of the science review. The Journal of Laryngology and Otology 2009;123,8:823-829. [2] Oates J. Auditory-perceptual evaluation of disordered voice quality: pros, cons and future directions. Folia Phoniatrica et Logopaedica 2009;61,1:49-56. [3] Maryn et al. Meta-analysis on acoustic voice quality measures. J Acoust Soc Am 2009; 126, 5: 2619-2634. [4] Vaz Freitas et al. Correlation Between Acoustic and Audio-Perceptual Measures. J Voice 2015;29,3:390.e1 [5] “Multi-Dimensional Voice Program (MDVP) Model 5105. Software Instruction Manual”, Kay PENTAX, A Division of PENTAX Medical Company, 2 Bridgewater Lane, Lincoln Park, NJ 07035-1488 USA, November 2007. [6] Dejonckere PH, Bradley P, Clemente P, Cornut G, Crevier-Buchman L, Friedrich G, Van De Heyning P, Remacle M, Woisard V. A basic protocol for functional assessment of voice pathology, especially for investigating the efficacy of (phonosurgical) treatments and evaluating new assessment techniques. Guideline elaborated by the Comm. on Phoniatrics of the European Laryngological Society (ELS). Eur Arch Otorhinolaryngol 2001;258:77–82. [7] Kreiman et al. Voice Quality Perception. J Speech Hear Res 1993;36:21-4 [8] De Cheveigné A, Kawahara H. YIN, a fundamental frequency estimator for speech and music. J. Acoust. Soc. Amer. 202; 111,4:1917. [9] Shrivastav et al. Measuring breathiness. J Acoust Soc Am 2003;114,4:2217-2224. [10] Saenz-Lechon et al. Automatic Assessment of voice quality according to the GRBAS scale. Eng Med Biol Soc Ann 2006;1:2478-2481. [11] Fredouille et al. Back-and-forth methodology for objective voice quality assessment: from/to expert knowledge to/from automatic classification of dysphonia. EURASIP J Appl Si Pr 2009.Campus de Excelencia Internacional Andalucía Tech, Universidad de Málaga. Ministerio de Economía y Competitividad, Projecto No. TIN2013-47276-C6-2-R

Spectral and localization properties of random bipartite graphs

Bipartite graphs are often found to represent the connectivity between the components of many systems such as ecosystems. A bipartite graph is a set of $n$ nodes that is decomposed into two disjoint subsets, having $m$ and $n-m$ vertices each, such that there are no adjacent vertices within the same set. The connectivity between both sets, which is the relevant quantity in terms of connections, can be quantified by a parameter $\alpha\in[0,1]$ that equals the ratio of existent adjacent pairs over the total number of possible adjacent pairs. Here, we study the spectral and localization properties of such random bipartite graphs. Specifically, within a Random Matrix Theory (RMT) approach, we identify a scaling parameter $\xi\equiv\xi(n,m,\alpha)$ that fixes the localization properties of the eigenvectors of the adjacency matrices of random bipartite graphs. We also show that, when $\xi10$) the eigenvectors are localized (extended), whereas the localization--to--delocalization transition occurs in the interval $1/10<\xi<10$. Finally, given the potential applications of our findings, we round off the study by demonstrating that for fixed $\xi$, the spectral properties of our graph model are also universal.Comment: 17 pages, 10 figure

Maerl grounds : habitats of high biodiversity in European seas

The BIOMAERL programme is a 3-year collaborative programme between laboratories in UK, Spain, France and Malta which began in February 1996. Its main plans are described in the workplan. A full inventory of the biological composition (biodiversity) of maerl bed assemblages in these regions therefore has yet to be completed, but progress is outlined below.peer-reviewe

Natural estrogens enhance the engraftment of human hematopoietic stem and progenitor cells in immunodeficient mice

Hematopoietic Stem and Progenitor Cells are crucial in the maintenance of lifelong production of all blood cells. These Stem Cells are highly regulated to maintain homeostasis through a delicate balance between quiescence, self-renewal and differentiation. However, this balance is altered during the hematopoietic recovery after Hematopoietic Stem and Progenitor Cell Transplantation. Transplantation efficacy can be limited by inadequate Hematopoietic Stem Cells number, poor homing, low level of engraftment, or limited self-renewal. As recent evidences indicate that estrogens are involved in regulating the hematopoiesis, we sought to examine whether natural estrogens (estrone or E1, estradiol or E2, estriol or E3 and estetrol or E4) modulate human Hematopoietic Stem and Progenitor Cells. Our results show that human Hematopoietic Stem and Progenitor Cell subsets express estrogen receptors, and whose signaling is activated by E2 and E4 on these cells. Additionally, these natural estrogens cause different effects on human Progenitors in vitro. We found that both E2 and E4 expand human Hematopoietic Stem and Progenitor Cells. However, E4 was the best tolerated estrogen and promoted cell cycle of human Hematopoietic Progenitors. Furthermore, we identified that E2 and, more significantly, E4 doubled human hematopoietic engraftment in immunodeficient mice without altering other Hematopoietic Stem and Progenitor Cells properties. Finally, the impact of E4 on promoting human hematopoietic engraftment in immunodeficient mice might be mediated through the regulation of mesenchymal stromal cells in the bone marrow niche. Together, our data demonstrate that E4 is well tolerated and enhances human reconstitution in immunodeficient mice, directly by modulating human Hematopoietic Progenitor properties and indirectly by interacting with the bone marrow niche. This application might have particular relevance to ameliorate the hematopoietic recovery 3 after myeloablative conditioning, especially when limiting numbers of Hematopoietic Stem and Progenitor Cells are available

Emery-Dreifuss muscular dystrophy Type 1 is associated with a high risk of malignant ventricular arrhythmias and end-stage heart failure

BACKGROUND AND AIMS: Emery-Dreifuss muscular dystrophy (EDMD) is caused by variants in EMD (EDMD1) and LMNA (EDMD2). Cardiac conduction defects and atrial arrhythmia are common to both, but LMNA variants also cause end-stage heart failure (ESHF) and malignant ventricular arrhythmia (MVA). This study aimed to better characterise the cardiac complications of EMD variants. METHODS: Consecutively referred EMD variant-carriers were retrospectively recruited from 12 international cardiomyopathy units. MVA and ESHF incidence in male and female variant-carriers was determined. Male EMD variant-carriers with a cardiac phenotype at baseline (EMDCARDIAC) were compared to consecutively recruited male LMNA variant-carriers with a cardiac phenotype at baseline (LMNACARDIAC). RESULTS: Longitudinal follow-up data were available for 38 male and 21 female EMD variant-carriers (mean [SD] ages 33.4 [13.3] and 43.3 [16.8] years, respectively). Nine (23.6%) males developed MVA and five (13.2%) developed ESHF during a median [IQR] follow-up of 65.0 [24.3, 109.5] months. No female EMD variant-carrier had MVA or ESHF, but nine (42.8%) developed a cardiac phenotype at a median [IQR] age of 58.6 [53.2, 60.4] years. Incidence rates for MVA were similar for EMDCARDIAC and LMNACARDIAC (4.8 and 6.6 per 100 person-years, respectively; log-rank p = 0.49). Incidence rates for ESHF were 2.4 and 5.9 per 100 person-years for EMDCARDIAC and LMNACARDIAC, respectively (log-rank p = 0.09). CONCLUSIONS: Male EMD variant-carriers have a risk of progressive heart failure and ventricular arrhythmias similar to that of male LMNA variant-carriers. Early implantable cardioverter defibrillator implantation and heart failure drug therapy should be considered in male EMD variant-carriers with cardiac disease

ST6GAL1-mediated aberrant sialylation promotes prostate cancer progression

Aberrant glycosylation is a universal feature of cancer cells, and cancer-associated glycans have been detected in virtually every cancer type. A common change in tumour cell glycosylation is an increase in α2,6 sialylation of N-glycans, a modification driven by the sialyltransferase ST6GAL1. ST6GAL1 is overexpressed in numerous cancer types, and sialylated glycans are fundamental for tumour growth, metastasis, immune evasion, and drug resistance, but the role of ST6GAL1 in prostate cancer is poorly understood. Here, we analyse matched cancer and normal tissue samples from 200 patients and verify that ST6GAL1 is upregulated in prostate cancer tissue. Using MALDI imaging mass spectrometry (MALDI-IMS), we identify larger branched α2,6 sialylated N-glycans that show specificity to prostate tumour tissue. We also monitored ST6GAL1 in plasma samples from >400 patients and reveal ST6GAL1 levels are significantly increased in the blood of men with prostate cancer. Using both in vitro and in vivo studies, we demonstrate that ST6GAL1 promotes prostate tumour growth and invasion. Our findings show ST6GAL1 introduces α2,6 sialylated N-glycans on prostate cancer cells and raise the possibility that prostate cancer cells can secrete active ST6GAL1 enzyme capable of remodelling glycans on the surface of other cells. Furthermore, we find α2,6 sialylated N-glycans expressed by prostate cancer cells can be targeted using the sialyltransferase inhibitor P-3FAX-Neu5Ac. Our study identifies an important role for ST6GAL1 and α2,6 sialylated N-glycans in prostate cancer progression and highlights the opportunity to inhibit abnormal sialylation for the development of new prostate cancer therapeutics