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Background: Studies on cognition in children with Down Syndrome (Trisomy 21) have described poor performance manipulating numbers. Elisabetta Monari's (2002) research suggest that considering mathematics as a universe of exploration beyond written arithmetic can offer them an opportunity for “human flourishing” (Su 2020). Geometry offers a suitable starting point. Objective: Exploring the use of geometrical activities for introducing children with T21 to integer and rational numbers. Design: A series of 7 workshops were designed to convey arithmetic concepts (counting, comparing and measuring) through plane geometry activities. Setting and Participants: Seven children aged 9 to 13, who had already completed a 3-year work on geometry, participated in the workshops held at the venue of the Spanish association Sesdown in Zaragoza, in leisure time. Data collection and analysis: Raw data consisted of 1) written reflections of lived experience (Van Manen 1990) by all adults participating in the experiment, following a shared protocol observation guide; 2) photographs; and 3) edited short videos. Results: Understanding of counting, cardinality, multiplication, measure and simple fractions was enhanced by previous geometrical conceptions, which came to the forefront and were reinforced. Moreover, activities enhanced speech. Cheerful engagement and increased awareness was also observed. Conclusions: The integration of arithmetic and geometry helps children with T21 to enter the mathematical world with understanding and pleasure. Primary school mathematics focuses on written arithmetic, but geometry is hidden in many educational aids and models. Explicit geometrical work can help inclusion of all children in mathematics school lessons.

9 Pág., The developmental failures occurring between blastocyst hatching and implantation in farm ungulates are a major cause of pregnancy losses. At the expanded blastocyst stage, three cell lineages emerge in the embryo: trophoblast, hypoblast and epiblast, the latter being the most vulnerable during post-hatching development. Transforming growth factor beta (TGFβ) signaling pathway is involved in hypoblast and epiblast development; however, previous in vitro functional studies are limited to the expanded blastocyst stage. In this study, we have analyzed the effect of TGFβ inhibition with 10, 20 or 40 μM SB431542 during ovine post-hatching developmental period using a recently developed culture system able to recapitulate major developmental landmarks. We have found a negative effect of TGFβ inhibition on hypoblast and epiblast development that could be partially reverted by Rho-associated protein kinase (ROCK) inhibitor Y-27632. Our findings provide new insights into the molecular networks regulating embryo development beyond the expanded blastocyst and could help to elucidate the causes of early pregnancy losses in farm ungulates., This work has been funded by the projects StG-757886-ELONGAN from the European Research Council to PBA and PID2021-122153NA-I00 from the Spanish Ministry of Science and Innovation to PRI.

The higher order degrees are Alexander-type invariants of complements to an affine plane curve. In this paper, we characterize the vanishing of such invariants for a curve 𝐶 given as a transversal union of plane curves 𝐶′ and 𝐶′′ in terms of the finiteness and the vanishing properties of the invariants of 𝐶′ and 𝐶′′, and whether or not they are irreducible. As a consequence, we prove that the multivariable Alexander polynomial Δmulti 𝐶 is a power of (𝑡 − 1), and we characterize when Δmulti 𝐶 = 1 in terms of the defining equations of 𝐶′ and 𝐶′′. Our results impose obstructions on the class of groups that can be realized as fundamental groups of complements of a transversal union of curves, Gobierno de Aragón, Grant/Award Number: E22_20R; Ministerio de Ciencia e Innovación, Grant/Award Number: PID2020-114750GB-C31; Simons Foundation, Grant/Award Number: AMS-Simons Travel Grant

In this paper we explore conditions for the complement of a fibered-type curve to be a free product of cyclic groups. We exhibit a Zariski pair of curves in $\mathbb{C}^2$ with only nodes as singularities (and the same singularities at infinity) whose complements have non-isomorphic fundamental groups, one of them being free. This shows that the position of singularities also affects this problem and hence the sufficient conditions involve more than local invariants. We also study the homotopy type of projective curve complements whose fundamental groups are free products of cyclic groups. Finally we describe the CW-complex structure of certain fibered-type curve complements., 14 pages. Comments are welcome and greatly appreciated

Background: Despite increasing evidence suggesting that pulmonary arterial hypertension (PAH) is a complex disease involving vasoconstriction, thrombosis, inflammation, metabolic dysregulation and vascular proliferation, all the drugs approved for PAH mainly act as vasodilating agents. Since excessive TGF-β signaling is believed to be a critical factor in pulmonary vascular remodeling, we hypothesized that blocking TGFβ-activated kinase 1 (TAK-1), alone or in combination with a vasodilator therapy (i.e., riociguat) could achieve a greater therapeutic benefit.Methods: PAH was induced in male Wistar rats by a single injection of the VEGF receptor antagonist SU5416 (20 mg/kg) followed by exposure to hypoxia (10%O2) for 21 days. Two weeks after SU5416 administration, vehicle, riociguat (3 mg/kg/day), the TAK-1 inhibitor 5Z-7-oxozeaenol (OXO, 3 mg/kg/day), or both drugs combined were administered for 7 days. Metabolic profiling of right ventricle (RV), lung tissues and PA smooth muscle cells (PASMCs) extracts were performed by magnetic resonance spectroscopy, and the differences between groups analyzed by multivariate statistical methods.Results:In vitro, riociguat induced potent vasodilator effects in isolated pulmonary arteries (PA) with negligible antiproliferative effects and metabolic changes in PASMCs. In contrast, 5Z-7-oxozeaenol effectively inhibited the proliferation of PASMCs characterized by a broad metabolic reprogramming but had no acute vasodilator effects. In vivo, treatment with riociguat partially reduced the increase in pulmonary arterial pressure (PAP), RV hypertrophy (RVH), and pulmonary vascular remodeling, attenuated the dysregulation of inosine, glucose, creatine and phosphocholine (PC) in RV and fully abolished the increase in lung IL-1β expression. By contrast, 5Z-7-oxozeaenol significantly reduced pulmonary vascular remodeling and attenuated the metabolic shifts of glucose and PC in RV but had no effects on PAP or RVH. Importantly, combined therapy had an additive effect on pulmonary vascular remodeling and induced a significant metabolic effect over taurine, amino acids, glycolysis, and TCA cycle metabolism via glycine-serine-threonine metabolism. However, it did not improve the effects induced by riociguat alone on pulmonary pressure or RV remodeling. None of the treatments attenuated pulmonary endothelial dysfunction and hyperresponsiveness to serotonin in isolated PA.Conclusion: Our results suggest that inhibition of TAK-1 induces antiproliferative effects and its addition to short-term vasodilator therapy enhances the beneficial effects on pulmonary vascular remodeling and RV metabolic reprogramming in experimental PAH.

This paper deals with cyclic covers of a large family of rational normal surfaces that can also be described as quotients of a product, where the factors are cyclic covers of algebraic curves. We use a generalization of Esnault-Viehweg method to show that the action of the monodromy on the first Betti group of the covering (and its Hodge structure) splits as a direct sum of the same data for some specific cyclic covers over $\mathbb{P}^1$. This has applications to the study of L\^e-Yomdin surface singularities, in particular to the action of the monodromy on the Mixed Hodge Structure, as well as to isotrivial fibered surfaces., Comment: Accepted in Publicacions Matem\`atiques

(1) Gingival inflammation is an ongoing challenge in tooth-supported fixed restorations, especially when the prosthetic margin does not consider the supracrestal tissues of patients. This case report aimed to present the case of a patient who was periodontally compromised due to a previous invasion of the supracrestal tissue attachment with fixed restorations and evaluate the healing response of periodontal tissues to a vertical edgeless preparation technique: bleeding upon probing (BOP), periodontal probing depth (PPD) and clinical attachment level (CAL). (2) After tooth preparation, the new restorations were adapted, this time without invading the supracrestal space of the patient, and CAD/CAM monolithic zirconia crowns were fabricated. (3) Optimal maturation of the soft tissue was observed, achieving correction of the marginal contour of periodontal tissues and improvement of periodontal indexes. (4) It can be concluded that the BOPT technique combined with a full digital workflow is a valid option for the correction and remodeling of gingival architecture. Sin financiación 3.160 Q2 JCR 2021 0.550 Q2 SJR 2022 No data IDR 2021 UEM

Based on "Philoctetes", the tragic play by Sophocles, the poet Seamus Heaney creates his own version in "The Cure at Troy" to present the political and social problems in Northern Ireland during the period that became known euphemistically as ‘the Troubles’. This paper aims to highlight the significance of Heaney’s play in the final years of the conflict. Heaney uses the classical Greek play to bring to light the plight and suffering of the Northern Irish people as a consequence of the atavistic and sectarian violence between the unionist and nationalist communities. Nevertheless, Heaney also provides possible answers that allow readers to harbour a certain degree of hope towards peace and the future in Northern Ireland.

Chronic obstructive pulmonary disease (COPD), whose main risk factor is cigarette smoking (CS), is one of the most common diseases globally. Some COPD patients also develop pulmonary hypertension (PH), a severe complication that leads to premature death. Evidence suggests reactive oxygen species (ROS) involvement in COPD and PH, especially regarding pulmonary artery smooth muscle cells (PASMC) dysfunction. However, the effects of CS-driven oxidative stress on the pulmonary vasculature are not completely understood. Herein we provide evidence on the effects of CS extract (CSE) exposure on PASMC regarding ROS production, antioxidant response and its consequences on vascular tone dysregulation. Our results indicate that CSE exposure promotes mitochondrial fission, mitochondrial membrane depolarization and increased mitochondrial superoxide levels. However, this superoxide increase did not parallel a counterbalancing antioxidant response in human pulmonary artery (PA) cells. Interestingly, the mitochondrial superoxide scavenger mitoTEMPO reduced mitochondrial fission and membrane potential depolarization caused by CSE. As we have previously shown, CSE reduces PA vasoconstriction and vasodilation. In this respect, mitoTEMPO prevented the impaired nitric oxide-mediated vasodilation, while vasoconstriction remained reduced. Finally, we observed a CSE-driven downregulation of the Cyb5R3 enzyme, which prevents soluble guanylyl cyclase oxidation in PASMC. This might explain the CSE-mediated decrease in PA vasodilation. These results provide evidence that there might be a connection between mitochondrial ROS and altered vasodilation responses in PH secondary to COPD, and strongly support the potential of antioxidant strategies specifically targeting mitochondria as a new therapy for these diseases, The Spanish Ministerio de Ciencia e Innovacion, ´ Programa Retos en Investigacion ´ (grant number PID2019-104406RB-100) to MJC provided the financial support for the conduct of the research included in this manuscript. Garantia Juvenil program from Comunidad de Madrid contributed with the research assistant contract to M-R, O

Il progetto Erasmus+ ANFoMAM, "Imparare dai bambini per formare insegnanti nell'area della matematica" è nato da un incontro tra un gruppo di insegnanti responsabili delle materie matematiche nei corsi di laurea in Formazione Primaria in diverse università in Francia, Italia e Spagna. L'incontro è avvenuto all'interno del Simposio dal titolo "Oltre l'alfabetizzazione numerica" che si è svolto presso il 5° Congresso Internazionale di Scienze dell'Educazione e dello Sviluppo (Santander, maggio 2017), in cui sono state condivise diverse esperienze che si stavano realizzando nelle istituzioni di formazione iniziale e continua degli insegnanti di istruzione elementare. Ciò che è stato osservato in questi paesi è che, in generale, i partecipanti ai corsi di laurea in formazione primaria avevano avuto un cattivo rapporto con la matematica durante i loro anni di studio, spesso accompagnato da sentimenti di rifiuto o angoscia, oltre ad aver acquisito una visione della matematica ridotta al calcolo e alle procedure meccaniche. Evitando il falso dibattito tra il concentrarsi sul miglioramento delle competenze matematiche o l'insegnamento delle tecniche didattiche, tutte le iniziative presentate al Congresso di Santander hanno perseguito l'obiettivo comune di fornire agli insegnanti sia una profonda comprensione dei concetti di base della matematica sia le risorse didattiche necessarie per l'insegnamento efficace in classe. I ricercatori hanno convenuto che era l'Università che avrebbe dovuto fornire a questi insegnanti in formazione nuove esperienze con la matematica, in modo che potessero trasmettere ai bambini la fiducia e l'entusiasmo necessari per imparare. La progettazione e la realizzazione di esperienze di questo tipo è l'obiettivo fondamentale del progetto ANFoMAM, che è stato finanziato dal programma Erasmus+ di Partenariati Strategici nel settore dell'istruzione superiore, e al quale hanno partecipato le seguenti istituzioni: Université de Bordeaux (Istituto Superiore Nazionale di Insegnanti e Istruzione dell'Accademia di Bordeaux), in Francia; Università Roma Tre (Dipartimento di Scienze della Formazione), in Italia; Università di Saragozza e Università Pubblica di Navarra, in Spagna; Associazione Sesdown, che si dedica alla ricerca nell'educazione dei bambini con Trisomia 21, sempre in Spagna, e l'Associazione ToKalon, che opera in Italia nell'ambito della formazione continua degli insegnanti in servizio.

The Erasmus+ ANFoMAM project, "Learning from children to train teachers in the area of mathematics" was born from a meeting between a group of teachers responsible for mathematics subjects in Primary Education degree courses in different universities in France, Italy and Spain. The meeting took place within the Symposium entitled "Beyond numerical literacy" which took place at the 5th International Congress of Education and Development Sciences (Santander, May 2017), in which different experiences that were taking place in initial and continuing education institutions for elementary education teachers were shared. What was observed in these countries is that, in general, participants in primary education degree courses had a poor relationship with mathematics during their student years, often accompanied by feelings of rejection or distress, as well as having acquired a view of mathematics reduced to calculation and mechanical procedures. All the initiatives presented at the Santander Congress pursued the common goal of providing teachers with both a deep understanding of the basic concepts of mathematics and the educational resources necessary for effective teaching in the classroom. The researchers agreed that it was the university that should provide these trainee teachers with new experiences with mathematics, so that they could give children the confidence and enthusiasm to learn. The design and implementation of experiences of this type is the fundamental objective of the ANFoMAM project, which was funded by the Erasmus+ program of Strategic Partnerships in the Higher Education Sector, and in which the following institutions participated: Université de Bordeaux (Institute National Superior of Teachers and Education of the Academy of Bordeaux), in France; Roma Tre University (Department of Education), in Italy; University of Zaragoza and Public University of Navarra, in Spain; Sesdown Association, which is dedicated to research in the education of children with Trisomy 21, also in Spain, and the ToKalon Association, which operates in Italy in the field of continuous training of in-service teachers. This innovative didactic material is a didactic guide for teacher mathematical training, made up of 6 mathematical workshops: 1. Understanding of arithmetic algorithms. 2. Resolution of arithmetic problems. 3. Relationship between arithmetic and geometry. 4. Mental calculation and use of the calculator. 5. History of mathematics and its teaching. 6. Geometry.

Rationale: Cigarette smoke is considered the chief leading cause of chronic obstructive pulmonary disease (COPD). Its impact on the progressive deterioration of airways has been extensively studied...

HIV and Schistosoma infections have been individually associated with pulmonary vascular disease. Co-infection with these pathogens is very common in tropical areas, with an estimate of six million people co-infected worldwide. However, the effects of HIV and Schistosoma co-exposure on the pulmonary vasculature and its impact on the development of pulmonary vascular disease are largely unknown. Here, we have approached these questions by using a non-infectious animal model based on lung embolization of Schistosoma mansoni eggs in HIV-1 transgenic (HIV) mice. Schistosome-exposed HIV mice but not wild-type (Wt) counterparts showed augmented pulmonary arterial pressure associated with markedly suppressed endothelial-dependent vasodilation, increased endothelial remodeling and vessel obliterations, formation of plexiform-like lesions and a higher degree of perivascular fibrosis. In contrast, medial wall muscularization was similarly increased in both types of mice. Moreover, HIV mice displayed an impaired immune response to parasite eggs in the lung, as suggested by decreased pulmonary leukocyte infiltration, small-sized granulomas, and augmented residual egg burden. Notably, vascular changes in co-exposed mice were associated with increased expression of proinflammatory and profibrotic cytokines, including IFN-γ and IL-17A in CD4+ and γδ T cells and IL-13 in myeloid cells. Collectively, our study shows for the first time that combined pulmonary persistence of HIV proteins and Schistosoma eggs, as it may occur in co-infected people, alters the cytokine landscape and targets the vascular endothelium for aggravated pulmonary vascular pathology. Furthermore, it provides an experimental model for the understanding of pulmonary vascular disease associated with HIV and Schistosoma co-morbidity. This research was supported by the Cardiovascular Medical Research and Education Fund (to G.B. and A.C.), and grants from the Spanish Ministry of Science and Innovation (PID2020- 117939RB-I00 to A.C., RTI2018-095673-B-I00 to E.F.-M. and PID2019-107363RB-I00 to F.P.V.), Fundación Contra la Hipertensión Pulmonar-EMPATHY and Comunidad de Madrid (B2017/BMD-3727 to A.C.). S.M.-G. was supported by a predoctoral fellowship from Complutense University. R.K. avails Career development award from American Heart Association (19CDA34730030); B.B.G. avails NHLBI NIH grant R01HL135872. R.S. was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)-Projektnummer 268555672-SFB1213, project A08 and B04. Sí

Vitamin D (VitD) receptor regulates the expression of several genes involved in signaling pathways affected in pulmonary hypertension (PH). VitD deficiency is highly prevalent in PH, and low levels are associated with poor prognosis. We investigated if VitD deficiency may predispose to or exacerbate PH. Male Wistar rats were fed with a standard or a VitD-free diet for 5 wk. Next, rats were further divided into controls or PH, which was induced by a single dose of Su-5416 (20 mg/kg) and exposure to hypoxia (10% O2) for 2 wk. VitD deficiency had no effect on pulmonary pressure in normoxic rats, indicating that, by itself, it does not trigger PH. However, it induced several moderate but significant changes characteristic of PH in the pulmonary arteries, such as increased muscularization, endothelial dysfunction, increased survivin, and reduced bone morphogenetic protein ( Bmp) 4, Bmp6, DNA damage-inducible transcript 4, and K+ two - pore domain channel subfamily K member 3 ( Kcnk3) expression. Myocytes isolated from pulmonary arteries from VitD-deficient rats had a reduced whole voltage-dependent potassium current density and acid-sensitive (TASK-like) potassium currents. In rats with PH induced by Su-5416 plus hypoxia, VitD-free diet induced a modest increase in pulmonary pressure, worsened endothelial function, increased the hyperreactivity to serotonin, arterial muscularization, decreased total and TASK-1 potassium currents, and further depolarized the pulmonary artery smooth muscle cell membrane. In human pulmonary artery smooth muscle cells from controls and patients with PH, the active form of VitD calcitriol significantly increased KCNK3 mRNA expression. Altogether, these data strongly suggest that the deficit in VitD induces pulmonary vascular dysfunction.

All metazoans depend on the consumption of O2 by the mitochondrial oxidative phosphorylation system (OXPHOS) to produce energy. In addition, the OXPHOS uses O2 to produce reactive oxygen species that can drive cell adaptations1,2,3,4, a phenomenon that occurs in hypoxia4,5,6,7,8 and whose precise mechanism remains unknown. Ca2+ is the best known ion that acts as a second messenger9, yet the role ascribed to Na+ is to serve as a mere mediator of membrane potential10. Here we show that Na+ acts as a second messenger that regulates OXPHOS function and the production of reactive oxygen species by modulating the fluidity of the inner mitochondrial membrane. A conformational shift in mitochondrial complex I during acute hypoxia11 drives acidification of the matrix and the release of free Ca2+ from calcium phosphate (CaP) precipitates. The concomitant activation of the mitochondrial Na+/Ca2+ exchanger promotes the import of Na+ into the matrix. Na+ interacts with phospholipids, reducing inner mitochondrial membrane fluidity and the mobility of free ubiquinone between complex II and complex III, but not inside supercomplexes. As a consequence, superoxide is produced at complex III. The inhibition of Na+ import through the Na+/Ca2+ exchanger is sufficient to block this pathway, preventing adaptation to hypoxia. These results reveal that Na+ controls OXPHOS function and redox signalling through an unexpected interaction with phospholipids, with profound consequences for cellular metabolism., This research has been financed by Spanish Government grants (ISCIII and AEI agencies, partially funded by the European Union FEDER/ERDF) CSD2007-00020 (RosasNet, Consolider-Ingenio 2010 programme to A.M.-R. and J.A.E.); CP07/00143, PS09/00101, PI12/00875, PI15/00107 and RTI2018-094203-B-I00 (to A.M.-R.); CP12/03304 and PI15/01100 (to L.M.); CP14/00008, CPII19/00005 and PI16/00735 (to J.E.); SAF2016-77222-R (to A. Cogolludo); PI17/01286 (to P.N.); SAF2015-65633-R, RTI2018-099357-B-I00 and CB16/10/00282 (to J.A.E.); RTI2018-095793-B-I00 (to M.G.L.); and SAF2017-84494-2-R (to J.R.-C.), by the European Union (ITN GA317433 to J.A.E. and MC-CIG GA304217 to R.A.-P.), by grants from the Comunidad de Madrid B2017/BMD-3727 (to A. Cogolludo) and B2017/BMD-3827 (to M.G.L.), by a grant from the Fundación Domingo Martínez (to M.G.L. and A.M.-R.), by the Human Frontier Science Program grant HFSP-RGP0016/2018 (to J.A.E.), by grants from the Fundación BBVA (to R.A.-P. and J.R.-C.), by the UCM-Banco Santander grant PR75/18-21561 (to A.M.-d.-P.), by the Programa Red Guipuzcoana de Ciencia, Tecnología e Información 2018-CIEN-000058-01 (to J.R.-C.) and from the Basque Government under the ELKARTEK Program (grant no. KK-2019/bmG19 to J.R.-C.), by the Swiss National Science Foundation (SNF) grant 310030_124970/1 (to A.B.), by a travel grant from the IIS-IP (to P.H.-A.) and by the COST actions TD0901 (HypoxiaNet) and BM1203 (EU-ROS). The CNIC is supported by the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (Spanish Government award SEV-2015-0505). CIC biomaGUNE is supported by the María de Maeztu Units of Excellence Program from the Spanish Government (MDM-2017-0720). P.H.-A. was a recipient of a predoctoral FPU fellowship from the Spanish Government. E.N. is a recipient of a predoctoral FPI fellowship from the Universidad Autónoma de Madrid (UAM). A.M.-R., L.M. and J.E. are supported by the I3SNS or ‘Miguel Servet’ programmes (ISCIII, Spanish Government; partially funded by the FEDER/ERDF).

Objective: Pulmonary arterial hypertension (PAH), one of the major complications of systemic sclerosis (SSc), is a rare disease with unknown etiopathogenesis and noncurative treatments. As mice deficient in P-selectin glycoprotein ligand 1 (PSGL-1) develop a spontaneous SSc-like syndrome, we undertook this study to analyze whether they develop PAH and to examine the molecular mechanisms involved. Methods: Doppler echocardiography was used to estimate pulmonary pressure, immunohistochemistry was used to assess vascular remodeling, and myography of dissected pulmonary artery rings was used to analyze vascular reactivity. Angiotensin II (Ang II) levels were quantified by enzyme-linked immunosorbent assay, and Western blotting was used to measure Ang II type 1 receptor (ATR), ATR, endothelial cell nitric oxide synthase (eNOS), and phosphorylated eNOS expression in lung lysates. Flow cytometry allowed us to determine cytokine production by immune cells and NO production by endothelial cells. In all cases, there were 4–8 mice per experimental group. Results: PSGL-1 mice showed lung vessel wall remodeling and a reduced mean ± SD expression of pulmonary ATR (expression ratio [relative to β-actin] in female mice age >18 months: wild-type mice 0.799 ± 0.508 versus knockout mice 0.346 ± 0.229). With aging, female PSGL-1 mice had impaired up-regulation of estrogen receptor α (ERα) and developed lung vascular endothelial dysfunction coinciding with an increase in mean ± SEM pulmonary Ang II levels (wild-type 48.70 ± 5.13 pg/gm lung tissue versus knockout 78.02 ± 28.09 pg/gm lung tissue) and a decrease in eNOS phosphorylation, leading to reduced endothelial NO production. These events led to a reduction in the pulmonary artery acceleration time:ejection time ratio in 33% of aged female PSGL-1 mice, indicating pulmonary hypertension. Importantly, we found expanded populations of interferon-γ–producing PSGL-1 T cells and B cells and a reduced presence of regulatory T cells. Conclusion: The absence of PSGL-1 induces a reduction in Treg cells, NO production, and ERα expression and causes an increase in Ang II in the lungs of female mice, favoring the development of PAH., Spanish Ministry of Economy and Competitiveness (grants SAF2015-69396-R, SAF2011-28150, and SAF2014-55399) and the Spanish Ministry of Health and Instituto de Salud Carlos III (cofinanced by Fondos FEDER; grants AC17-00027, FIS-PI14-01698, FIS-PI17-01819, and FIS-PI12-01578, Red de Investigación de Enfermedades Reumáticas [RIER] RD12/0009/0017). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Ministerio de Economía, Industria y Competitividad, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505))

In this paper we study Sigma-invariants of even Artin groups of FC-type, extending some known results for right-angled Artin groups. In particular, we define a condition that we call the strong n-link condition for a graph Gamma and prove that it gives a sufficient condition for a character chi : A(Gamma) -> Z to satisfy chi] is an element of Sigma(n)(A(Gamma), Z). This implies that the kernel A(Gamma)(chi) = ker chi is of type FPn. We prove the homotopical version of this result as well and discuss partial results on the converse. We also provide a general formula for the free part of H-n(A(Gamma)(chi); F) as an Ft(+/- 1)]-module with the natural action induced by chi. This gives a characterization of when H-n(A(Gamma)(chi); F) is a finite dimensional vector space over F.

In this work we study smooth complex quasi-projective varieties whose fundamental group is a free product of cyclic groups. In particular, we prove the existence of a (maybe irrational) pencil from the quasi-projective variety to a Riemann surface (endowed with an orbifold structure) which induces an isomorphism of (orbifold) fundamental groups. The orbifold structure is given by the multiple fibers of the pencil. Associated with this result, we prove addition-deletion Lemmas of fibers in the pencil which explain how these operations affect the fundamental group of the quasi-projective variety. Our methods also allow us to produce curves whose fundamental group of their complement is a free product of cyclic groups, generalizing classical results on $C_{p,q}$ curves and torus type projective sextics, and showing how general this phenomenon is., Comment: 29 pages. Comments are welcome and greatly appreciated

The Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its sublineages pose a new challenge to healthcare systems worldwide due to its ability to efficiently spread in immunized populations and its resistance to currently available therapies. COVID-19, although targeting primarily the respiratory system, is also now well established that later affects every organ in the body. Most importantly, despite the available therapy and vaccine-elicited protection, the long-term consequences of viral infection in breakthrough and asymptomatic individuals are areas of concern. In the past two years, investigators accumulated evidence on how the virus triggers our immune system and the molecular signals involved in the cross-talk between immune cells and structural cells in the pulmonary vasculature to drive pathological lung complications such as endothelial dysfunction and thrombosis. In the review, we emphasize recent updates on the pathophysiological inflammatory and immune responses associated with SARS-CoV-2 infection and their potential long-term consequences that may consequently lead to the development of pulmonary vascular diseases.

(computer-aided design-computer-aided manufacturing) CAD/CAM monolithic restorations connected to zirconia abutments manufactured with a chairside workflow are becoming a more common restorative option. However, their mechanical performance is still uncertain. The aim of this study was to evaluate the mechanical behavior of a combination of a zirconia abutment and monolithic all-ceramic zirconia and lithium disilicate crown manufactured with a chairside workflow, connected to titanium implants with two types of internal connection—tube in tube connection and conical connection with platform switching. They were thermally cycled from 5 C to 55 C and were subjected to a static and fatigue test following ISO 14801. The fractured specimens from the fatigue test were examined by SEM (scanning electron microscopy). Simulations of the stress distribution over the different parts of the restorative complex during the mechanical tests were evaluated by means of (finite element analysis) FEA. The mechanical performance of the zirconia abutment with an internal conical connection was higher than that of the tube in tube connection. Additionally, the use of disilicate or zirconia all-ceramic chairside CAD/CAM monolithic restorations has similar results in terms of mechanical fracture and fatigue resistance. Stress distribution affects the implant/restoration complex depending on the connection design. Zirconia abutments and monolithic restorations seem to be highly reliable in terms of mechanical resistance. Sin financiación 3.623 JCR (2020) Q1, 17/80 Metallurgy & Metallurgical Engineering 0.682 SJR (2020) Q2, 128/448 Condensed Matter Physics No data IDR 2020 UEM

[Background and Purpose]: The NO/cGMP pathway represents a major physiological signalling controlling tone in pulmonary arteries (PA), and drugs activating this pathway are used to treat pulmonary arterial hypertension. Kv channels expressed in PA smooth muscle cells (PASMCs) are key determinants of vascular tone. We aimed to analyse the contribution of Kv1.5 and Kv7 channels in the electrophysiological and vasodilating effects evoked by NO donors and the GC stimulator riociguat in PA., [Experimental Approach]: Kv currents were recorded in isolated rat PASMCs using the patch‐clamp technique. Vascular reactivity was assessed in a wire myograph., [Key Results]: The NO donors diethylamine NONOate diethylammonium (DEA‐NO) and sodium nitroprusside hyperpolarized the membrane potential and induced a bimodal effect on Kv currents (augmenting the current between −40 and −10 mV and decreasing it at more depolarized potentials). The hyperpolarization and the enhancement of the current were suppressed by Kv7 channel inhibitors and by the GC inhibitor ODQ but preserved when Kv1.5 channels were inhibited. Additionally, DEA‐NO enhanced Kv7.5 currents in COS7 cells expressing the KCNQ5 gene. Riociguat increased Kv currents at all potentials ≥−40 mV and induced membrane hyperpolarization. Both effects were prevented by Kv7 inhibition. Likewise, PA relaxation induced by NO donors and riociguat was attenuated by Kv7 inhibitors., [Conclusions and Implications]: NO donors and riociguat enhance Kv7 currents, leading to PASMC hyperpolarization. This mechanism contributes to NO/cGMP‐induced PA vasodilation. Our study identifies Kv7 channels as a novel mechanism of action of vasodilator drugs used in the treatment of pulmonary arterial hypertension., This work was funded by Ministerio de Economía y Competitividad grants (SAF2016‐77222R to F.P.‐V. and A.C. and SAF2016‐75021‐R to C.V. and T.G.), the Cardiovascular Medical Research and Education Fund (A.C.), Fundación Contra la Hipertensión Pulmonar‐EMPATHY, Comunidad de Madrid (B2017/BMD‐3727 to A.C. and L.M.), and Instituto de Salud Carlos III (PI15/01100 to L.M. and CB/11/00222 to C.V.) with funds from the European Union (Fondo Europeo de Desarrollo Regional FEDER). G.M.‐P., M.C., and S.E.‐R. are supported by CIBERES, Universidad Complutense and FPU grants.

K + channels play a fundamental role regulating membrane potential of pulmonary artery (PA) smooth muscle cells and their impairment is a common feature in pulmonary arterial hypertension (PAH). K + voltage-gated channel subfamily Q ( KCNQ1-5 ) or Kv7 channels and their regulatory subunits subfamily E (KCNE) regulatory subunits are known to regulate vascular tone, but whether Kv7 channel function is impaired in PAH and how this can affect the rationale for targeting Kv7 channels in PAH remains unknown. Here, we have studied the role of Kv7/KCNE subunits in rat PA and their possible alteration in PAH. Using the patch-clamp technique, we found that the total K + current is reduced in PA smooth muscle cells from pulmonary hypertension animals (SU5416 plus hypoxia) and Kv7 currents made a higher contribution to the net K + current. Likewise, enhanced vascular responses to Kv7 channel modulators were found in pulmonary hypertension rats. Accordingly, KCNE4 subunit was highly upregulated in lungs from pulmonary hypertension animals and patients. Additionally, Kv7 channel activity was enhanced in the presence of Kv1.5 and TASK-1 channel inhibitors and this was associated with an increased KCNE4 membrane abundance. Compared with systemic arteries, PA showed a poor response to Kv7 channel modulators which was associated with reduced expression and membrane abundance of Kv7.4 and KCNE4. Our data indicate that Kv7 channel function is preserved and KCNE4 is upregulated in PAH. Therefore, compared with other downregulated channels, the contribution of Kv7 channels is increased in PAH resulting in an enhanced sensitivity to Kv7 channel modulators. This study provides insight into the potential usefulness of targeting Kv7 channels in PAH.

The dysregulation of K+ channels is a hallmark of pulmonary arterial hypertension (PAH). Herein, the channelome was analyzed in lungs of patients with PAH in a public transcriptomic database. Sixty six (46%) mRNA encoding cationic channels were dysregulated in PAH with most of them downregulated (83%). The principal component analysis indicated that dysregulated cationic channel expression is a signature of the disease. Changes were very similar in idiopathic, connective tissue disease and congenital heart disease associated PAH. This analysis 1) is in agreement with the widely recognized pathophysiological role of TASK1 and KV1.5, 2) supports previous preliminary reports pointing to the dysregulation of several K+ channels including the downregulation of KV1.1, KV1.4, KV1.6, KV7.1, KV7.4, KV9.3 and TWIK2 and the upregulation of KCa1.1 and 3) points to other cationic channels dysregulated such as Kv7.3, TALK2, CaV1 and TRPV4 which might play a pathophysiological role in PAH. The significance of other changes found in Na+ and TRP channels remains to be investigated.

International audience; In this paper, we present a new format for mathematical workshops for pre-service teachers (PSTs)that seek to bring their university mathematical training closer to the school classroom reality whileaddressing issues such as confidence and their previous experiences of maths at school. The aim isto provide the participants with a group lived experience in order to change both their beliefs aboutthe nature of mathematics and their attitude towards teaching it. The results of the implementation ofan initial version of the workshops in a pilot phase of the project are presented here.

Reactive oxygen species (ROS) are frequently seen as pathological agents of oxidative stress. However, ROS are not always deleterious and can also act as cell signaling molecules. Vascular oxygen sensing and signaling during fetal-to-neonatal circulatory transition is a remarkable example of the physiological regulatory actions of ROS. The fetal relative hypoxic environment induces hypoxic pulmonary vasoconstriction (HPV) and ductus arteriosus (DA) relaxation favoring the presence of high pulmonary vascular resistance and right-to-left ductal shunt. At birth, the increase in oxygen tension causes relaxation of pulmonary arteries (PAs) and normoxic DA vasoconstriction (NDAV), thus diverting blood flow to the lungs. Although the response to changes in oxygen tension is diametrically opposite, the mechanisms responsible for HPV and NDAV appear to be the result of a similar interaction between triggering and modulating factors that lead to an increase in cytosolic Ca2+ concentration and Ca2+ sensitization of the contractile apparatus. Growing evidence points to an increase in ROS (mitochondria- and/or NADPH-derived superoxide and/or H2O2), leading to inhibition of voltage-gated K+ channels, membrane depolarization, and activation of voltage-gated L-type Ca2+ channels as critical events in the signaling pathway of both HPV and NDAV. Several groups of investigators have completed this pathway adding other elements such as neutral sphingomyelinase-derived ceramide, the sarcoplasmic/endoplasmic reticulum (through ryanodine and inositol 1,4,5-trisphosphate receptors), Rho kinase-mediated Ca2+ sensitization, or transient receptor potential channels. The present review focus on the role of ROS as mediators of the homeostatic oxygen sensing system during fetal and neonatal life not only in the PAs and DA but also in systemic arteries.

espanolEste articulo demostrara que el taller de escritura de Philip Hobsbaum, a modo y semejanza de un grupo similar en el Reino Unido, ensalzo a Seamus Heaney como poeta. Su resena sobre ‘A Group Anthology’ desperto en el un interes por contar con un grupo de escritores que actuarian de estimulo y critica constructiva. Entre estos aspirantes a escritores destacaba el joven Seamus Heaney, que habia publicado algunos poemas en revistas universitarias y diarios locales bajo el seudonimo de Incertus. Desde el principio, el se unio al entorno del llamado ‘Belfast Group’, y su participacion en las reuniones del taller, asi como las ensenanzas y los continuos estimulos de Hobsbaum, tuvieron una enorme influencia en sus inicios como poeta. El origen campesino de Heaney, su educacion catolica y su pertenencia a una comunidad minoritaria y discriminada, son factores que, unidos al contexto politico y social en Irlanda del Norte en esa epoca, incidieron decisivamente en su creacion artistica EnglishThis article will demonstrate how Philip Hobsbaum’s Belfast writing group, modelled on a similar group in the UK, defined Seamus Heaney as a poet. His review of ‘A Group Anthology’ in 1963 sparked in him an enthusiasm for a writers’ group which would provide encouragement and critical criticism from fellow writers. The young Seamus Heaney stood out among these aspiring writers in the Belfast Group; he had published a few poems in student magazines and local newspapers under the pseudonym Incertus. From the outset, his participation in the workshop sessions, along with Hobsbaum’s teachings and continuous encouragement, were enormously influential in his emergence as a poet. Heaney’s rural origins, his Catholic education and his belonging to a minority community which was being discriminated against, were factors that, together with the political and social context of Northern Ireland at that time, exercised a significant impact on his artistic creation

It is widely known that people with Down syndrome have difficulties transitioning from a basic understanding of counting and cardinality to more advanced arithmetic skills. This is commonly address...

Smoking is considered the chief leading cause of chronic obstructive pulmonary disease (COPD). Its impact on the progressive deterioration of the airways has been extensively studied. However, its direct effects on pulmonary vasculature have not been studied in deep, in part due to the classic conception that vascular damage is a consequence of alveolar hypoxia and loss of capillary bed. We have used different molecular and cell biology approaches, as well as tissue studies from in vivo models and human samples to analyse how cigarette smoke extract (CSE) regulated pulmonary arterial cells phenotypic modulation, particularly on human fibroblasts and smooth muscle cells. Our results demonstrate that CSE exposure has direct effects on hPAFib and hPASMC, promoting a senescent phenotype that in turn contributes to increase the proliferative potential of non-exposed cells. Using traction force microscopy, wire myography and patch-clamp techniques, we demonstrate that CSE affects cell contractility and dysregulates the expression and activity of the voltage-gated K+ channel Kv7.4. This ultimately contributes to limit vascular responses impairing vasoconstriction and endothelium-dependent and independent relaxation. Additionally, the levels of this channel are diminished in the lungs of smoke-exposed mice and COPD patients. These findings greatly enhance knowledge about pulmonary diseases, in particular COPD, and open a new line of study related to the exploitation of these mechanisms as therapeutic targets.

We explicitly compute the homology groups with coefficients in a field of characteristic zero of cocyclic subgroups or even Artin groups of FC-type. We also give some partial results in the case when the coefficients are taken in a field of prime characteristic., 18 pages, 2 figures. To appear in AGT

KWe used AngII-infused mice treated with two selective KAngII increased KWe unravelled a new role for K

The large K

Informe elaborado por el equipo europeo ANFoMAM coordinado por Inmaculada Lizasoain Esta publicación en formato digital incluye los siguientes puntos: Siete cuestionarios diseñados en el marco del proyecto y dirigidos a docentes en formación inicial y continua, orientados a conocer sus conocimientos, creencias y actitudes hacia las matemáticas y su enseñanza antes de la puesta en práctica de un taller; Implementación en las instituciones del proyecto; Análisis de resultados y conclusiones. Este informe ha sido realizado en el ámbito del proyecto Erasmus + 2018 nº 2018-1-ES01-KA203-050986 ANFoMAM Aprender de los niños para formar a los maestros en el área de Matemáticas, cofinanciado por la Unión Europea.

Informe elaborado por el equipo europeo ANFoMAM coordinado por Inmaculada Lizasoain Esta publicación en formato digital incluye los siguientes puntos: Siete cuestionarios diseñados en el marco del proyecto y dirigidos a docentes en formación inicial y continua, orientados a conocer sus conocimientos, creencias y actitudes hacia las matemáticas y su enseñanza antes de la puesta en práctica de un taller; Implementación en las instituciones del proyecto; Análisis de resultados y conclusiones. Este informe ha sido realizado en el ámbito del proyecto Erasmus + 2018 nº 2018-1-ES01-KA203-050986 ANFoMAM "Aprender de los niños para formar a los maestros en el área de Matemáticas", cofinanciado por la Unión Europea.

In this work, we study a family of Cremona transformations of weighted projective planes which generalize the standard Cremona transformation of the projective plane. Starting from special plane projective curves we construct families of curves in weighted projective planes with special properties. We explain how to compute the fundamental groups of their complements, using the blow-up-down decompositions of the Cremona transformations, we find examples of Zariski pairs in weighted projective planes (distinguished by the Alexander polynomial). As another application of this machinery we study a family of singularities called weighted Le–Yomdin, which provide infinitely many examples of surface singularities with a rational homology sphere link. To end this paper we also study a family of surface singularities generalizing Brieskorn–Pham singularities in a different direction. This family contains infinitely many examples of integral homology sphere links, answering a question by Nemethi.

Informe elaborado por el equipo europeo ANFoMAM coordinado por Inmaculada Lizasoain Esta publicación en formato digital incluye los siguientes puntos: Siete cuestionarios diseñados en el marco del proyecto y dirigidos a docentes en formación inicial y continua, orientados a conocer sus conocimientos, creencias y actitudes hacia las matemáticas y su enseñanza antes de la puesta en práctica de un taller; Implementación en las instituciones del proyecto; Análisis de resultados y conclusiones. Este informe ha sido realizado en el ámbito del proyecto Erasmus + 2018 nº 2018-1-ES01-KA203-050986 ANFoMAM Aprender de los niños para formar a los maestros en el área de Matemáticas, cofinanciado por la Unión Europea.

[Background and Purpose]: KV1.3 channels are expressed in vascular smooth muscle cells (VSMCs), where they contribute to proliferation rather than contraction and participate in vascular remodelling. KV1.3 channels are also expressed in macrophages, where they assemble with KV1.5 channels (KV1.3/KV1.5), whose activation generates a KV current. In macrophages, the KV1.3/KV1.5 ratio is increased by classical activation (M1). Whether these channels are involved in angiotensin II (AngII)-induced vascular remodelling, and whether they can modulate the macrophage phenotype in hypertension, remains unknown. We characterized the role of KV1.3 channels in vascular damage in hypertension., [Experimental Approach]: We used AngII-infused mice treated with two selective KV1.3 channel inhibitors (HsTX[R14A] and [EWSS]ShK). Vascular function and structure were measured using wire and pressure myography, respectively. VSMC and macrophage electrophysiology were studied using the patch-clamp technique; gene expression was analysed using RT-PCR., [Key Results]: AngII increased KV1.3 channel expression in mice aorta and peritoneal macrophages which was abolished by HsTX[R14A] treatment. KV1.3 inhibition did not prevent hypertension, vascular remodelling, or stiffness but corrected AngII-induced macrophage infiltration and endothelial dysfunction in the small mesenteric arteries and/or aorta, via a mechanism independent of electrophysiological changes in VSMCs. AngII modified the electrophysiological properties of peritoneal macrophages, indicating an M1-like activated state, with enhanced expression of proinflammatory cytokines that induced endothelial dysfunction. These effects were prevented by KV1.3 blockade., [Conclusions and Implications]: We unravelled a new role for KV1.3 channels in the macrophage-dependent endothelial dysfunction induced by AngII in mice which might be due to modulation of macrophage phenotype., This work was funded by the Ministerio de Economía y Competitividad; AEI-FEDER, EU grants: SAF2016-75021-R and PID2019-104366RB-C21 (to C.V.), SAF2016-80305-P (to A.M.B. and M.S.), and SAF2016-77222-R (to A.C.); Instituto de Salud Carlos III CIBERCV program: CB16/11/00286 (to M.S.) and CB/11/00222 (to C.V.); Consejo Superior de Investigaciones Científicas grants: PIE 201820E104 and 2019AEP148 (to C.V.) and Comunidad de Madrid grant: B2017/BMD-3676-AORTASANA (to M.S.) and B2017/BMD-3727 (to A.C.) with funds co-financed by ERDF (FEDER) Funds from the European Commission, “A way of making Europe”; and Comunidad de Madrid-Universidad Autónoma de Madrid grant: SI1-PJ1-2019-00321 (to A.B.G.-R.).

We consider the structure of classes of curves on a projective simply connected surface for which fundamental groups of the complements admit free quotients having rank greater than one with irreducible components belonging to a selected subset the effective cone of the surface. In particular we show a finiteness result for such classes if the ranks of free quotients of the fundamental groups with components in the subset of effective cone are sufficiently large., Comment: Substantial revision. Final version to appear in Proc. Edinburgh Mathematical Society

Para mí, este trabajo “Problemas de distancia euclídea” ha sido un desafíofascinante ya que abarca muchas ramas de las matemáticas. Combina técnicas deAlgebra, Geometría, Análisis Numérico, Probabilidad e incluso la Parte Computacional (implementación de algoritmos)Vamos a dar primero una breve descripción de la geometría euclídea y geometría proyectiva.El objetivo de este trabajo es explicar de los procedimientos de calibración deimágenes, la mayoría de los cuales se basan en el modelo de cámara estenopeica,y este modelo a su vez se basa en la geometría proyectiva.Gracias al estudio de la geometría epipolar, podremos dar una respuesta a la pregunta:¿Cómo encontrar un punto (del espacio) en 3D que mejor se ajuste a los puntos de imagen medidos, es decir, sus proyecciones sobre dos planos imagen?Por último, describiremos algunos algoritmos que son necesarios para la resolución y corrección deimágenes (ya que en la práctica es difícil medir con precisión las coordenadas de los puntos imagen)

Current approved therapies for pulmonary hypertension (PH) aim to restore the balance between endothelial mediators in the pulmonary circulation. These drugs may exert vasodilator effects on poorly oxygenated vessels. This may lead to the derivation of blood perfusion towards low ventilated alveoli, i.e., producing ventilation-perfusion mismatch, with detrimental effects on gas exchange. The aim of this study is to analyze the oxygen-sensitivity in vitro of 25 drugs currently used or potentially useful for PH. Additionally, the study analyses the effectiveness of these vasodilators in the pulmonary vs. the systemic vessels. Vasodilator responses were recorded in pulmonary arteries (PA) and mesenteric arteries (MA) from rats and in human PA in a wire myograph under different oxygen concentrations. None of the studied drugs showed oxygen selectivity, being equally or more effective as vasodilators under conditions of low oxygen as compared to high oxygen levels. The drugs studied showed low pulmonary selectivity, being equally or more effective as vasodilators in systemic than in PA. A similar behavior was observed for the members within each drug family. In conclusion, none of the drugs showed optimal vasodilator profile, which may limit their therapeutic efficacy in PH. This work was supported by grants from Mineco (SAF2011-28150, SAF2016-77222, PID2019- 107363RB-I00), Instituto de Salud Carlos III (PI15/01100, FIS PI14/01733) with funds from the European Union (Fondo Europeo de Desarrollo Regional FEDER) and Fundación contra la Hipertensión Pulmonar (Empathy project). D.M.-C., M.C., G.M.-P. and S.E.-R. were funded by a Formación de Personal Investigador grant (BES-2012-051904), Universidad Complutense, Ciberes grant and a FPU grant from Ministerio de Educación, respectively. Sí

Informe elaborado por el equipo europeo ANFoMAM coordinado por Inmaculada Lizasoain Esta publicación en formato digital incluye los siguientes puntos: Siete cuestionarios diseñados en el marco del proyecto y dirigidos a docentes en formación inicial y continua, orientados a conocer sus conocimientos, creencias y actitudes hacia las matemáticas y su enseñanza antes de la puesta en práctica de un taller; Implementación en las instituciones del proyecto; Análisis de resultados y conclusiones. Este informe ha sido realizado en el ámbito del proyecto Erasmus + 2018 nº 2018-1-ES01-KA203-050986 ANFoMAM Aprender de los niños para formar a los maestros en el área de Matemáticas, cofinanciado por la Unión Europea.

Esnault-Viehweg developed the theory of cyclic branched coverings $\tilde X\to X$ of smooth surfaces providing a very explicit formula for the decomposition of $H^1(\tilde X,\mathbb{C})$ in terms of a resolution of the ramification locus. Later, the first author applies this to the particular case of coverings of $\mathbb{P}^2$ reducing the problem to a combination of global and local conditions on projective curves. In this paper we extend the above results in three directions: first, the theory is extended to surfaces with quotient singularities, second the ramification locus can be partially resolved and need not be reduced, and finally global and local conditions are given to describe the irregularity of cyclic branched coverings of the weighted projective plane. The techniques required for these results are conceptually different and provide simpler proofs for the classical results. For instance, the local contribution comes from certain modules that have the flavor of quasi-adjunction and multiplier ideals on singular surfaces. As an application, a Zariski pair of curves on a singular surface is described. In particular, we prove the existence of two cuspidal curves of degree 12 in the weighted projective plane $\mathbb{P}^2_{(1,1,3)}$ with the same singularities but non-homeomorphic embeddings. This is shown by proving that the cyclic covers of $\mathbb{P}^2_{(1,1,3)}$ of order 12 ramified along the curves have different irregularity. In the process, only a partial resolution of singularities is required., to appear in Indiana Univ. Math. J