Exact solution of variable coefficient mixed hyperbolic partial differential problems

AbstractThis paper is concerned with the construction of exact series solution of mixed variable coefficient hyperbolic problems

Vascular Effects of Current and Novel Antimigraine Drugs

Migraine is a highly prevalent and disabling neurovascular disorder, that predominantly affects women, thought to be associated with a dysfunctional activation of the trigeminovascular system. Despite the high prevalence of migraine, not all patients respond to current treatment. Moreover, the gold standard for acute treatment (“triptans”), are contraindicated in patients with cardiovascular disease due to their action in coronary blood vessels and migraine patients have higher risk of cardiovascular events. Additionally, the drugs available for the preventative treatment were not originally developed for migraine. Thus, novel treatments that do not act on the coronary blood vessels and are developed based on the pathophysiology of migraine are needed. In this thesis, we set out to investigate whether the novel antimigraine drugs atogepant, erenumab, lasmiditan and ubrogepant act on the blood vessels. We also studied whether the antihypertensive propranolol, currently given as migraine preventative acts on the trigeminovascular system. Our results show that atogepant, erenumab, lasmiditan and ubrogepant are all devoid of vascular effects and that propranolol modulates the trigeminovascular system in a sex dependent manner

Late Quaternary tectono-sedimentary processes on an isolated offshore high marginal platform (NW Iberian Continental Margin)

Studies of the most surficial sedimentary record from passive continental margins provide crucial knowledge about sedimentary dynamics and its changes through recent geological times. These studies allow understanding in detail the influence of both tectonic activity and long-term bottom-current circulation over the Late Quaternary sedimentary dynamics. Using a large dataset of multibeam bathymetry, chirp and multi-channel seismic (MCS) records, ROV seabed direct observations and a magneto-chemical facies characterisation, we provide a well-dated record of the tectono-sedimentary processes on an isolated high marginal platform over the Late Quaternary. Our results display several structural and geomorphological features and tectonic pulses that indicate intense faulting, folding, and deformation of the most recent sedimentary cover. Furthermore, we document four main sedimentary systems acting at the study area and controlled by different water masses (MOW, LSW and NADW): the (hemi)pelagic, bottom current-controlled (hemi)pelagic, contourite and downslope sedimentary systems; as well as a new typology of contourite associated to giant depressions, named as pockmarks-related drift. The record also shows erosive features and extremely low sedimentation rates for the last 172 cal ka BP. Results suggest that the topographic configuration of the high marginal platform and reorganizations of the water masses associated to climate changes causes a constriction of the water masses that induce an enhancement of the bottom-current activity, favouring erosion, winnowing and redistribution of sediments. Therefore, this study provides new insight into the tectonic control and bottom current activity effect over the Late Quaternary sedimentary cover from an isolated and elevate offshore morphostructural province, located at the Galician Continental Margin.publishe

Application of multivariate statistical analyses to Itrax core scanner data for the identification of deep-marine sedimentary facies: a case study in the Galician Continental Margin

The validity and usefulness of multivariate statistical tools for the facies characterization in deep-marine environments have been applied on the geochemical, sedimentological and magnetic data from a piston core extracted from the Transitional Zone in the Galician Continental Margin. The combination of geochemical profiles of Fe, Mn, Ti, Ba and Ca and magnetic susceptibility (MS) obtained using the ItraxTM Core Scanner at the University of Vigo, together with the grain-size, grey level and R (red) G (green) B (blue) colour analyses have allowed characterizing and classifying the sediments of the core PC13-3 using SPSS package v. 23. Cluster Analysis (CA) displays, in the first level of the hierarchy, two major groups that correspond with clay-silt and sand facies. In a second level, it is possible to observe six subfacies that match de visu preliminary classification and allowed us to complete and improve the characterization and the facies limits in the whole core. Discriminant Analysis (DA) confirmed the validity of the cluster analyses and enhanced the results of the classification. The Principal Component Analysis (PCA) shows four principal components: coarse lithogenic fraction (PC1), fine lithogenic fraction (PC2), high density fraction (PC3) and biogenic fraction (PC4). These results are in concordance with the Pearson correlation coefficient and the SEM observations. In general terms, the results confirm the utility of the multivariate statistical methods applied on high resolution geochemical and magnetic data acquired with ItraxTM corer scanner, as a quick and complementary tool in sedimentary facies analysis and description in deep marine environments.publishe

Gender aspects of CGRP in migraine

Background: Migraine is two to three times more prevalent in women than in men, but the mechanisms involved in this gender disparity are still poorly understood. In this respect, calcitonin gene-related peptide (CGRP) plays a key role in migraine pathophysiology and, more recently, the functional interactions between ovarian steroid hormones, CGRP and the trigeminovascular system have been recognized and studied in more detail. Aims: To provide an overview of CGRP studies that have addressed gender differences utilizing animal and human migraine preclinical research models to highlight how the female trigeminovascular system responds differently in the presence of varying ovarian steroid hormones. Conclusions: Gender differences are evident in migraine. Several studies indicate that fluctuations of ovarian steroid hormone (mainly estrogen) levels modulate CGRP in the trigeminovascular system during different reproductive milestones. Such interactions need to be considered when conducting future animal and human experiments, since these differences may contribute to the development of gender-specific therapies

Tree vigour influences secondary growth but not responsiveness to climatic variability in Holm oak

Many tree species from Mediterranean regions have started to show increased rates of crown defoliation, reduced groth, and dieback associated with the increase in temperatures and changes in the frequency and intensity of drought events experienced during the last decades. In this regard, Quercus ilex L. subsp. ballota (Desf.) (Holm oak), despite being a drought-tolerant species widely distributed in the Mediterranean basin, it has recently started to show acute signs of decline, extended areas from Spain being affected. However, few studies have assessed the role of climatic variability (i.e., temperature, precipitation, and drought) on the decline and resilience of Holm oak. Here, we measured secondary growth of seventy Holm oaks from a coppice stand located in central Spain. Sampled trees had different stages of decline, so they were classified into four vigour groups considering their crown foliar lost: healthy (0%), low defoliated (25%), highly defoliated (25 70%), and dying (70 100%). Our results showed that during the study period (1980 2009) the highly defoliated and dying Holm oaks grew significantly less than their healthy and low defoliated neighbours, suggesting permanent growth reduction in the less vigorous individuals. Despite these differences, all four vigour groups showed similar responses to climatic variations, especially during winter and late spring early summer seasons, and similar resilience after severe drought events, managing to significantly recover to pre-drought growth rates after only two years. Our findings, hence, illustrate that tree vigour influences secondary growth but not responsiveness to climatic variability in Holm oak. Still, as reduced growth rates are frequently associated with the process of tree mortality, we conclude that the less vigorous Holm oaks might not be able to cope with future water stress conditions, leading to increased mortality rates among this emblematic Mediterranean specie

Pharmacological analysis of the increases in heart rate and diastolic blood pressure produced by (S)-isometheptene and (R)-isometheptene in pithed rats

Background: Isometheptene is a sympathomimetic drug effective in acute migraine treatment. It is composed of two enantiomers with diverse pharmacological properties. This study investigated in pithed rats the cardiovascular effects of (S)- isometheptene and (R)-isometheptene, and the pharmacological profile of the more potent enantiomer. Methods: The effects of i.v. bolus injections (0.03, 0.1, 0.3, 1 and 3 mg/kg) of isometheptene racemate, (S)-isometheptene or (R)-isometheptene on heart rate and blood pressure were analyzed in control experiments. The enantiomer producing more pronounced tachycardic and/or vasopressor responses was further analyzed in rats receiving i.v. injections of prazosin (0.1 mg/kg), rauwolscine (0.3 mg/kg), propranolol (1 mg/kg) or intraperitoneal reserpine (5 mg/kg, -24 h). Results: Compared to (R)-isometheptene, (S)-isometheptene produced greater vasopressor responses, whilst both compounds equipotently increased heart rate. The tachycardic responses to (S)-isometheptene were abolished after propranolol, but remained unaffected by the other antagonists. In contrast, the vasopressor responses to (S)-isometheptene were practically abolished after prazosin. Interestingly, after reserpine, the tachycardic responses to (S)-isometheptene were abolished, whereas its vasopressor responses were attenuated and subsequently abolished by prazosin. Conclusions: The different cardiovascular effects of the isometheptene enantiomers are probably due to differences in their mechanism of action, namely: (i) a mixed sympathomimetic action for (S)-isometheptene (a tyramine-like action and a direct stimulation of α1-adrenoceptors); and (ii) exclusively a tyramine like action for (R)-isometheptene. Thus, (R)-isometheptene may represent a superior therapeutic benefit as an antimigraine agent

Vortex Dynamics and Defects in Simulated Flux Flow

We present the results of molecular dynamic simulations of a two-dimensional vortex array driven by a uniform current through random pinning centers at zero temperature. We identify two types of flow of the driven array near the depinning threshold. For weak disorder the flux array contains few dislocation and moves via correlated displacements of patches of vortices in a {\it crinkle} motion. As the disorder strength increases, we observe a crossover to a spatially inhomogeneous regime of {\it plastic} flow, with a very defective vortex array and a channel-like structure of the flowing regions. The two regimes are characterized by qualitatively different spatial distribution of vortex velocities. In the crinkle regime the distribution of vortex velocities near threshold has a single maximum that shifts to larger velocities as the driving force is increased. In the plastic regime the distribution of vortex velocities near threshold has a clear bimodal structure that persists upon time-averaging the individual velocities. The bimodal structure of the velocity distribution reflects the coexistence of pinned and flowing regions and is proposed as a quantitative signature of plastic flow.Comment: 12 pages, 13 embedded PostScript figure

Application of time-dependent density functional theory to optical activity

As part of a general study of the time-dependent local density approximation (TDLDA), we here report calculations of optical activity of chiral molecules. The theory automatically satisfies sum rules and the Kramers-Kronig relation between circular dichroism and optical rotatory power. We find that the theory describes the measured circular dichroism of the lowest states in methyloxirane with an accuracy of about a factor of two. In the chiral fullerene C_76 the TDLDA provides a consistent description of the optical absorption spectrum, the circular dichroism spectrum, and the optical rotatory power, except for an overall shift of the theoretical spectrum.Comment: 17 pages and 13 PostScript figure

Chronic lymphocytic leukemia patients with IGH translocations are characterized by a distinct genetic landscape with prognostic implications

Chromosome 14q32 rearrangements/translocations involving the immunoglobulin heavy chain (IGH) are rarely detected in chronic lymphocytic leukemia (CLL). The prognostic significance of the IGH translocation is controversial and its mutational profile remains unknown. Here, we present for the first time a comprehensive next-generation sequencing (NGS) analysis of 46 CLL patients with IGH rearrangement (IGHR-CLLs) and we demonstrate that IGHR-CLLs have a distinct mutational profile with recurrent mutations in NOTCH1, IGLL5, POT1, BCL2, FBXW7, ZMYM3, MGA, BRAF and HIST1H1E genes. Interestingly, BCL2 and FBXW7 mutations were significantly associated with this subgroup and almost half of BCL2, IGLL5 and HISTH1E mutations reported were previously identified in non-Hodgkin lymphomas. Notably, IGH/BCL2 rearrangements were associated with a lower mutation frequency and carried BCL2 and IGLL5 mutations, while the other IGHR-CLLs had mutations in genes related to poor prognosis (NOTCH1, SF3B1 and TP53) and shorter time to first treatment (TFT). Moreover, IGHR-CLLs patients showed a shorter TFT than CLL patients carrying 13q-, normal fluorescence in situ hybridization (FISH) and +12 CLL, being this prognosis particularly poor when NOTCH1, SF3B1, TP53, BIRC3 and BRAF were also mutated. The presence of these mutations not only was an independent risk factor within IGHR-CLLs, but also refined the prognosis of low-risk cytogenetic patients (13q-/normal FISH). Hence, our study demonstrates that IGHR-CLLs have a distinct mutational profile from the majority of CLLs and highlights the relevance of incorporating NGS and the status of IGH by FISH analysis to refine the risk-stratification CLL model