Coarsening Strategies for Unstructured Multigrid Techniques with Application to Anisotropic Problems

Over the years, multigrid has been demonstrated as an efficient technique for solving inviscid flow problems. However, for viscous flows, convergence rates often degrade. This is generally due to the required use of stretched meshes (i.e., the aspect ratio AR = Δy/Δx < < 1) in order to capture the boundary layer near the body. Usual techniques for generating a sequence of grids that produce proper convergence rates on isotropic meshes are not adequate for stretched meshes. This work focuses on the solution of Laplace's equation, discretized through a Galerkin finite-element formulation on unstructured stretched triangular meshes. A coarsening strategy is proposed and results are discussed

Shock and detonation modeling with the Mie-Grüneisen equation of state

We consider the numerical simulation of inviscid reactive flows with application to high density explosive detonation. The numerical model is based on the Euler equations and the Mie-Grüneisen equation of state extended to treat chemical energy release and expanded states. The equations are computed with a Roe-Glaister solver on a Cartesian mesh. We present results for two substances, a binder and an explosive. Our solution method is verified against the exact solution of the shock tube problem for solid materials. We show under what conditions a "physical" expansion shock can appear in this example. We then address the problem of modeling expanded states, and show results for a two-dimensional shock distraction around a sharp corner. In the last part of the paper, we introduce a detonation model that extends the Mie-Grüneisen equation of state to enable high explosive simulations without the complexity of mixture equations of state. We conclude with two examples of corner-turning computations carried out with a pressure-dependent reaction rate law

Impaired modulation of the cardiac L-type Ca2+ channel activity by ahnak-1 after myocardial infarction

Introduction: The L-type cardiac Ca2+ channel (Cav 1.2) is an important determinant of cardiac repolarization and the main source of activator Ca2+ during excitation-contraction coupling in cardiac cells. Its defective regulation is a major cause of arrhythmias and contractile dysfunction. We have recently shown that the cytoskeletal protein ahnak-1 modulates Ca2+ current through Cav 1.2 channels (ICaL) by interacting with the regulatory beta-subunit of the Cav 1.2 channel and that the genetic variant of ahnak-1 I5483T (previously Ile5236Thr), interferes with the beta-adrenergic stimulation of ICaL. Objective: To extend our study of the I5483T variant to ventricular cardiomyocytes dissociated from remodelled infarcted rat hearts (PMI). Methods: The patch-clamp technique was used to record ICaL from enzymatically dissociated ventricular cardiomyocytes from young (2-month-old) and six-month-old sham-operated and PMI rats. Results: Basal ICaL was increased from 11 ± 0.5 A/F in young cardiomyocytes to 14.6 ± 1.1 A/F and 15.7 ± 1 A/F in sham and PMI cardiomyocytes respectively, while isoprenaline (ISO, 1 µmol/L) further increased ICaL by 101 ± 6%, 109 ± 10% and 104 ± 12% respectively. When cells were intracellularly perfused with a peptide containing the mutated ahnak-1 sequence (10 µmol/L) basal ICaL was increased to 20 ± 1 A/F, 22 ± 2 A/F and 21 ± 2 A/F in young, sham and PMI cardiomyocytes respectively. In these cells ISO increased ICaL by 11 ± 4%, 33 ± 6% and 79 ± 12% respectively. Conclusion: Modulation of ICaL by ahnak-1is impaired by myocardial ischemia and remodelling. Since ahnak-1 and Cav 1.2 channels co-localize in the transverse T-tubule system, remodelling of T-tubules could affect the interaction of ahnak-1 with the regulatory beta subunit of these channels

Auto-inhibitory effects of an IQ motif on protein structure and function

The denuded IQ2 domain, i.e. myosin heavy chain not associated with regulatory light chains, exerts an inhibitory effect on myosin ATPase activity. In this study, we elaborated a structural explanation for this auto-inhibitory effect of IQ2 on myosin function. We employed analytical ultracentrifugation, circular dichroism, and surface plasmon resonance spectroscopy to investigate structural and functional properties of a myosin heavy chain (MYH) head-rod fragment aa664-915. MYH(664-915) was monomeric, adopted a closed shape, and bound essential myosin light chains (HIS-MLC-1) with low affinity to IQ1. Deletion of IQ2, however opened MYH(664-915). Four amino acids present in IQ2 could be identified to be responsible for this auto-inhibitory structural effect: alanine mutagenesis of I814, Q815, R819, and W827 stretched MYH(664-915) and increased 30fold the binding affinity of HIS-MLC-1 to IQ1. In this study we show, that denuded IQ2 favours a closed conformation of myosin with a low HIS-MLC-1 binding affinity. The collapsed structure of myosin with denuded IQ2 could explain the auto-inhibitory effects of IQ2 on enzymatic activity of myosin

Deep Multi-Segmentation Approach for the Joint Classification and Segmentation of the Retinal Arterial and Venous Trees in Color Fundus Images

Presented at the 4th XoveTIC Conference, A Coruña, Spain, 7–8 October 2021.[Abstract] The analysis of the retinal vasculature represents a crucial stage in the diagnosis of several diseases. An exhaustive analysis involves segmenting the retinal vessels and classifying them into veins and arteries. In this work, we present an accurate approach, based on deep neural networks, for the joint segmentation and classification of the retinal veins and arteries from color fundus images. The presented approach decomposes this joint task into three related subtasks: the segmentation of arteries, veins and the whole vascular tree. The experiments performed show that our method achieves competitive results in the discrimination of arteries and veins, while clearly enhancing the segmentation of the different structures. Moreover, unlike other approaches, our method allows for the straightforward detection of vessel crossings, and preserves the continuity of the arterial and venous vascular trees at these locations.This work was funded by Instituto de Salud Carlos III, Government of Spain, and the European Regional Development Fund (ERDF) of the European Union (EU) through the DTS18/00136 research project; Ministerio de Ciencia e Innovación, Government of Spain, through the RTI2018-095894-B-I00 and PID2019-108435RB-I00 research projects; Axencia Galega de Innovación (GAIN), Xunta de Galicia, ref. IN845D 2020/38; Xunta de Galicia and European Social Fund (ESF) of the EU through the predoctoral grant contracts ED481A-2017/328 and ED481A 2021/140; Consellería de Cultura, Educación e Universidade, Xunta de Galicia, through Grupos de Referencia Competitiva, grant ref. ED431C 2020/24; CITIC, Centro de Investigación de Galicia ref. ED431G 2019/01, is funded by Consellería de Educación, Universidade e Formación Profesional, Xunta de Galicia, through the ERDF (80%) and Secretaría Xeral de Universidades (20%)Xunta de Galicia; IN845D 2020/38Xunta de Galicia; ED481A-2017/328Xunta de Galicia; ED481A 2021/140Xunta de Galicia; ED431C 2020/24Xunta de Galicia; ED431G 2019/0

The Psychology of Beethoven and The Eroica Symphony

As a concert pianist and chapel organist, Beethoven rose to a fame in Vienna which allowed him patrons and friends who would support his compositions. One such patron was Count Waldstein, who claimed that Beethoven would inherit the spirit of Mozart in his famous prediction of Beethoven’s success. To study composition Beethoven turned to two prominent Viennese composers: Haydn and Salieri. As his fame grew, his health decreased until he was diagnosed with deafness and moved to Heiligenstadt. Here Beethoven wrote a letter to his brothers called the Heiligenstadt Testament, which was never sent but expressed his troubled mental state. Beethoven composed his Eroica Symphony in a time in his life when, accepting the onset of his deafness, he also experienced the onset of depression. The Eroica Symphony has threads of Heroism running throughout it, and tells the story of life over death. But a question remains surrounding the work: Who is the Hero

The Status of Human Rights Protection in Europe: It’s complicated

The UK has voted to leave the European Union and Prime Minister Theresa May has expressed her aversion to the European Convention on Human Rights, but confusion abounds as to what the current architecture of Europe is, let alone what it might look like in the future. This article seeks to provide a comprehensive overview of the development of supranational human rights protections in Europe and the status of the current quest for greater integration. In particular, the stalled movement towards the accession of the EU to the ECHR is examined and likened to a riddle: to avoid subjecting Member States to conflicting obligations, the ECHR must be granted ultimate authority in the field of human rights, but without compromising the autonomy of EU law. The article concludes with a conversation with Dr Sonia Morano-Foadi, whose extensive research into the European human rights institutions enables her to shed some light on the likelihood of the accession riddle ever being solved and to provide a prognosis for European rights protections in the future

Ablation of smooth muscle myosin heavy chain SM2 increases smooth muscle contractility and results in postnatal death in mice

The smooth muscle myosin heavy chains (SMHC) are motor proteins powering smooth muscle contraction. Alternate splicing of SHMC gene at the C-terminus produces SM1, and SM2 myosin isoforms; SM2 (200 kDa) contains a unique 9-amino-acid sequence at the carboxyl terminus, whereas SM1 (204 kDa) has a 43 amino acid non-helical tail region. To date the functional difference between C-terminal isoforms has not been established; therefore, we used an exon-specific gene targeting strategy and generated a mouse model specifically deficient in SM2. Deletion of exon-41 of the SMHC gene resulted in a complete loss of SM2 in homozygous (_SM2^-/-^_) mice, accompanied by a concomitant down-regulation of SM1 in bladders. While heterozygous (_SM2^+/-^_) mice appeared normal and fertile, _SM2^-/-^_ mice died within 30 days after birth. The peri-mortal _SM2^-/-^_ mice showed reduced body weight, distention of the bladder and alimentary tract, and end-stage hydronephrosis. Interestingly, strips from _SM2^-/-^_ bladders showed increased contraction to K^+^ depolarization or M3 receptor activation. These results suggest that SM2 myosin has a distinct functional role in smooth muscle, and the deficiency of SM2 increases smooth muscle contractility, and causes dysfunctions of smooth muscle organs, including the bladder that leads to the end-stage hydronephrosis and postnatal death

Acerca de la cuestión post-urbana : Una mirada sobre los procesos de trnasformación de la ciduad central de un área metropolitana: Buenos Aires

El presente trabajo forma parte de los resultados parciales de una serie de investigaciones en curso desarrolladas por los autores, cuyo objetivo es el estudio de las recientes transformaciones producidas sobre la ciudad de Buenos Aires como resultado de la generación de nuevas centralidades sobre los bordes de su área metropolitana.Evento también conocido bajo el nombre de "II Jornadas Platenses de Geografía"Facultad de Humanidades y Ciencias de la Educació