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We describe all 2-orbit skeletal polyhedra in classes $$2_0$$ 2 0 and $$2_2$$ 2 2 in $$\mathbb {E}^3$$ E 3 . Those in class $$2_2$$ 2 2 are continuous deformations of the three Petrie–Coxeter polyhedra and therefore are arranged in three families. Those in class $$2_0$$ 2 0 are the Petrie duals of the chiral polyhedra in $$\mathbb {E}^3$$ E 3 and are classified in six families.

We study chiral polyhedra in 3-dimensional geometries (Euclidean, hyperbolic, and projective) in a unified manner. This extends to hyperbolic and projective spaces some structural results in the classification of chiral polyhedra in Euclidean 3-space given in 2005 by Schulte. Then, we describe a way to produce examples with helical faces based on a classic Petrie–Coxeter construction, yielding a new family in $$\mathbb {S}^3$$ which is described exhaustively.

Sara Pastor was not included as an author in the original publication [...]

Introduction: Alpha-1 antitrypsin deficiency (AATD) is a rare respiratory condition characterized by abnormal inflammation, where neutrophils play a key role. Excessive neutrophil activation leads to an increase in the oxygen (O2) intake, causing local hypoxia and increased tissue-injury capacity. Tissue hypoxia is part of the inflammatory process so neutrophils can function effectively under these conditions. However, the mechanisms by which neutrophils mediate tissue damage under hypoxia remain unclear. The study aimed to determine whether hypoxia modifies the cytokine profile in AATD patients. Methods: Neutrophils from 22 AATD patients (6 MZ; 9 SZ; 7 ZZ) and 7 controls (MM) were exposed to hypoxia (1% O2) or normoxia (21% O2) for 4hrs. Pro- and anti-inflammatory cytokine levels were measured with a Luminex Bead-Based Multiplex Assay. Results: Neutrophils from AATD patients (SZ; ZZ) exposed to hypoxia showed an augmented proinflammatory cytokines release (IL-8, IL-12, IL-6, IL-23, IL-4, MIPα, MIPβ) compared to those of controls. Interestingly, the tumour necrosis factor (TNFα) is decreased in AATD patients compared to controls. Conclusion: Hypoxia increases the neutrophil release of proinflammatory cytokines in AATD patients compared to controls, contributing to lung damage in these patients. Funding: Sociedad Valenciana de Neumologia 2015 and 2017 and ISCIII PI17/01250 grants and European Regional Development Funds

A maniplex of rank n is a connected, n-valent, edge-coloured graph that generalises abstract polytopes and maps. If the automorphism group of a maniplex M partitions the vertex-set of M into k distinct orbits, we say that M is a k-orbit n-maniplex. The symmetry type graph of M is the quotient pregraph obtained by contracting every orbit into a single vertex. Symmetry type graphs of maniplexes satisfy a series of very specific properties. The question arises whether any pregraph of order k satisfying these properties is the symmetry type graph of some k-orbit maniplex. We answer the question when k = 2 .

A chiral polytope with Schlafli symbol $$\{p_1, \ldots , p_{n-1}\}$$ has at least $$2p_1 \cdots p_{n-1}$$ flags, and it is called tight if the number of flags meets this lower bound. The Schlafli symbols of tight chiral polyhedra were classified in an earlier paper, and another paper proved that there are no tight chiral n-polytopes with $$n \ge 6$$ . Here we prove that there are no tight chiral 5-polytopes, describe 11 families of tight chiral 4-polytopes, and show that every tight chiral 4-polytope covers a polytope from one of those families.

Gene therapy is an alternative therapy in many respiratory diseases with genetic origin and currently without curative treatment. After five decades of progress, many different vectors and gene editing tools for genetic engineering are now available. However, we are still a long way from achieving a safe and efficient approach to gene therapy application in clinical practice. Here, we review three of the most common rare respiratory conditions—cystic fibrosis (CF), alpha-1 antitrypsin deficiency (AATD), and primary ciliary dyskinesia (PCD)—alongside attempts to develop genetic treatment for these diseases. Since the 1990s, gene augmentation therapy has been applied in multiple clinical trials targeting CF and AATD, especially using adeno-associated viral vectors, resulting in a good safety profile but with low efficacy in protein expression. Other strategies, such as non-viral vectors and more recently gene editing tools, have also been used to address these diseases in pre-clinical studies. The first gene therapy approach in PCD was in 2009 when a lentiviral transduction was performed to restore gene expression in vitro; since then, transcription activator-like effector nucleases (TALEN) technology has also been applied in primary cell culture. Gene therapy is an encouraging alternative treatment for these respiratory diseases; however, more research is needed to ensure treatment safety and efficacy.

Maniplexes are combinatorial objects that generalize, simultaneously, maps on surfaces and abstract polytopes. We are interested on studying rotary maniplexes, that is, those having maximal 'rotational' symmetry. This note classifies rotary 4-dimensional maniplexes with the property of having exactly one facet, and gives examples and related results.

A map is said to be even-closed if all of its automorphisms act like even permutations on the vertex set. In this paper the study of even-closed regular maps is approached by analysing two distinguished families. The first family consists of embeddings of a well-known family of graphs on distinct orientable surfaces, whereas in the second family we consider all graphs having orientable-regular embeddings on a particular surface. In particular, the classification of even-closed orientable-regular embeddings of the complete bipartite graphs K n , n and classification of even-closed orientable-regular maps on the torus are given.

We present 35 open problems on combinatorial, geometric and algebraic aspects of k -orbit abstract polytopes. We also present a theory of rooted polytopes that has appeared implicitly in previous work but has not been formalized before.

In this paper we exhibit the first infinite family of abstract 4-polytopes whose connection groups are not string C-groups. In addition we present some new results on methods of representing the connection group of a polytope in terms of its automorphism group. We also analyze the connection groups of all of the pyramids over the finite regular 3-tori.

The first chiral polytope of full rank known was Roli’s cube, a rank 4 polytope discovered in 2014. Since then, other chiral polytopes of rank 4 have been studied. Here we present the first known chiral 5-polytope of full rank. Its 2-skeleton is the same as that of the Euclidean tessellation { 3 , 4 , 3 , 3 } with 24-cells.

In this paper we list three chiral 4-polytopes in Euclidean space, and show that this list is complete. This concludes the classification of chiral polytopes of full rank in 3-space. We also prove that these three chiral 4-polytopes are combinatorially chiral.

From a given abstract n-polytope P and a given integer k we derive two abstract polytopes Clk(P) and $${\widetilde {Cl}_k}\left( P \right)$$ of ranks n and n−1, respectively. These constructions generalise the truncation of convex polyhedra and the dual of a geometric construction yielding Petrie’s polyhedron {4,6|4}. We determine sufficient and necessary conditions to guarantee that Clk(P) and $${\widetilde {Cl}_k}\left( P \right)$$ are regular.

In this paper we describe an infinite chiral 4 -polytope in the Euclidean 3 -space. This builds on previous work of Bracho, Hubard and the author, where a finite chiral 4 -polytope in the Euclidean 4 -space is constructed. These two polytopes show that there are finite and infinite chiral polytopes of full rank as defined by McMullen.

Introduction: Alpha-1 antitrypsin (AATD) deficiency is an inherited condition that leads to decreased circulating AAT levels, significantly increasing the risk of lung and liver disease. AATD is underdiagnosed. Severity of symptoms in AATD patients are highly variable and neither protein levels nor phenotype are sufficient to identify which patients will develop lung and/or liver disease. Therefore, new strategies and biomarkers for early diagnosis and prognosis of the disease are needed. Rationale and Aims: MicroRNAs (miRNAs) regulate gene expression and have been associated with the pathogenesis of various lung and liver diseases. Circulating miRNAs may serve as diagnostic and prognostic biomarkers of the AATD. This study is aimed is to determine an expression profile of plasma miRNAs in AATD to serve as a diagnostic and prognostic tool for the disease. Material and Methods: Expression profile of plasma miRNAs was determined using GeneChip miRNA 3.0 Arrays (Affymetrix) in 37 patients with DAAT and 19 healthy volunteers. Differentially expressed miRNAs were validated by RT-qPCR in 34 DAAT patients and 14 healthy volunteers. Results: A profile of differentially expressed plasma miRNAs that can potentially serve as biomarkers for the diagnosis and prognosis of AATD was identified. Specifically, miRNA-122, miR-93, miR-107, miR-425 and miR-151a miRNAs have diagnostic value, while miRNA-17, miRNA-106a and miRNA-93 are elevated in patients with emphysema and miRNA-107 and miRNA-23b are increased in patients with liver disease. Conclusions: We have identified a genetic signature that differentiates the different risk groups and the presence of emphysema and hepatopathy in AATD patients.

Introduction: The emergence some years ago of the CRISPR/Cas9 system allowed gene therapy to be specific, versatile, cheap and approachable to almost every laboratory. Due to these features, many different genetic diseases such as cystic fibrosis or β-thalassemia have been addressed in cellular models using the CRISPR/Cas9 genetic editing tool. Alpha-1 antytripsin deficiency (AATD) is a rare genetic condition that can provoke respiratory and hepatic symptoms. The Z allele of SERPINA1 gene is a well-characterised point mutation that can trigger the whole pathology. Henceforth, Z mutation is a suitable target for genetic edition using CRISPR/Cas9 in order to develop a gene therapy to treat AATD. Aims and Objectives: The aim of this work is to set-up a CRISPR/Cas9 system to revert the Z mutation on in vitro models. Methods: Five different RNA guides were designed. Hek293 cells were transfected with the RNA guides and GFP using Lipofectamine 3000. After a 48 hour-incubation, transfection efficiency was estimated by fluorescence microscopy. Genomic DNA was isolated and the Z mutation locus was amplified by PCR. Gene editing efficiency was verified by the T7 endonuclease assay. Results: Transfection efficiency was estimated to be approximately 10-20%. After performing T7 endonuclease assay, the digested samples showed two smaller DNA fragments in the agarose gel, indicating that CRISPR/Cas9 system has produced a break in the genome at the Z mutation. Conclusion: SERPINA1 Z mutation can be targeted and edited by the CRISPR/Cas9 system in Hek293 cells with the RNA guides designed. This is the first step towards Z mutation correction in others AATD cellular models. Funding: SVN 2016 and 112/2016 SEPAR grants.

Several studies have shown that some rare respiratory diseases, such as alpha-1 antitrypsin deficiency (AATD), idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF), and primary ciliary dyskinesia (PCD) present oxidative stress (OS) and endoplasmic reticulum (ER) stress. Their involvement in these pathologies and the use of antioxidants as therapeutic agents to minimize the effects of OS are discussed in this review.

Several studies have shown the importance of oxidative stress (OS) in respiratory disease pathogenesis. It has been reported that the nasal epithelium may act as a surrogate for the bronchial epithelium in several respiratory diseases involving OS. However, the sample yields obtained from nasal biopsies are modest, limiting the number of parameters that can be determined. Flow cytometry has been widely used to evaluate cellular OS profiles. It has the advantage that analyses can be performed using a small amount of sample. Therefore, we aimed to set up a new method based on flow cytometry to assess the oxidative profile of human nasal epithelial cells which could be used in research on respiratory diseases. Levels of total nitric oxide, superoxide anion, peroxynitrite, and intracellular peroxides were measured. Reduced thiol levels, such as antioxidant-reduced glutathione and oxidative damaged lipids and proteins, were also analysed. The intracellular calcium levels, plasma membrane potential, apoptosis, and percentage of live cells were also studied. Finally, a strategy to evaluate the mitochondrial function, including mitochondrial hydrogen peroxide, superoxide anion, mitochondrial mass, and membrane potential, was set up. Using small amounts of sample and a non-invasive sampling technique, the described method enables the measurement of a comprehensive set of OS parameters in nasal epithelial cells, which could be useful in research on respiratory diseases.

By an equivelar toroid we understand a map satisfying the requirements of an abstract polyhedron on the 2-torus where all faces have a fixed number p of edges, and all vertices belong to a fixed number q of edges. We establish that if every regular toroid of type $$\{4,4\}$${4,4} admits a faithful and symmetric realisation in a metric space $$\mathcal {S}$$S then every equivelar toroid of type $$\{4,4\}$${4,4} admits a faithful and symmetric realisation in $$\mathcal {S}$$S. We exemplify this by showing that every equivelar toroid of type $$\{4,4\}$${4,4} admits faithful and symmetric realisations in the 3-sphere and in 3-dimensional projective space.

Lindero Atravesado field is located in Neuquen, western Argentina. It has been under development since 2012. Originally, its development was focused on conventional formations (Quintuco, Sierras Blancas and Lotena), considering the Punta Rosada and Lajas formations as geological traps. Development is now focused on these traps, especially in the northwest region the field, called the Lindero Atravesado Occidental. Fundamental challenges in the Occidental region of the field include optimum fluid engineering, avoiding shear-sensitive fluid systems, high PAD percentage and safe operational efficiency in deep HPHT wells. However, original frac designs were optimized through a traditional cycle of design and pressure-matching evaluations using a conventional frac simulator. Obtained fracture geometries were bounded in length and a considerable height growth was observed. Other studies used microseismic, sonic profiles or traceable sands, and showed fractures contained in height and longer fracture lengths than those obtained with the traditional adjusted model. A fracturing model coupled with microseismic interpretation allowed a better characterization of fracture geometry, vertical covering, effective production fracture length and drainage area efficiency, based on numerical production simulations and matching. The last point will have a direct impact on well spacing and future selection of in-fill locations. This paper will discuss a fully integrated approach for field planning optimization, starting with geosciences characterization, workover, stimulation and production history matching, with a direct impact on well gridding and estimated ultimate recovery (EUR) per well.

Maniplexes are combinatorial objects that generalize, simultaneously, maps on surfaces and abstract polytopes. We are interested on studying highly symmetric maniplexes, particularly those having maximal ‘rotational’ symmetry. This paper introduces an operation on polytopes and maniplexes which, in its simplest form, can be interpreted as twisting the connection between facets. This is first described in detail in dimension 4 and then generalized to higher dimensions. Since the twist on a maniplex preserves all the orientation preserving symmetries of the original maniplex, we apply the operation to reflexible maniplexes, to attack the problem of finding chiral polytopes in higher dimensions.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition that leads to decreased circulating alpha-1 antitrypsin (AAT) levels, significantly increasing the risk of serious lung and/or liver disease in children and adults, in which some aspects remain unresolved. METHODS: In this review, we summarise and update current knowledge on alpha-1 antitrypsin deficiency in order to identify and discuss areas of controversy and formulate questions that need further research. RESULTS: 1) AATD is a highly underdiagnosed condition. Over 120,000 European individuals are estimated to have severe AATD and more than 90% of them are underdiagnosed. CONCLUSIONS: 2) Several clinical and etiological aspects of the disease are yet to be resolved. New strategies for early detection and biomarkers for patient outcome prediction are needed to reduce morbidity and mortality in these patients; 3) Augmentation therapy is the only specific approved therapy that has shown clinical efficacy in delaying the progression of emphysema. Regrettably, some countries reject registration and reimbursement for this treatment because of the lack of larger randomised, placebo-controlled trials. 4) Alternative strategies are currently being investigated, including the use of gene therapy or induced pluripotent stem cells, and non-augmentation strategies to prevent AAT polymerisation inside hepatocytes. This work was supported by SEPAR 201/2013 and ISCIII PI17/01250 grants and European Regional Development Funds. Sí

Primary ciliary dyskinesia (PCD) is a rare heterogenous condition that causes progressive suppurative lung disease, chronic rhinosinusitis, chronic otitis media, infertility and abnormal situs. ‘Better Experimental Approaches to Treat Primary Ciliary Dyskinesia’ (BEAT-PCD) is a network of scientists and clinicians coordinating research from basic science through to clinical care with the intention of developing treatments and diagnostics that lead to improved long-term outcomes for patients. BEAT-PCD activities are supported by EU funded COST Action (BM1407). The second BEAT-PCD conference, and third PCD training school were held jointly in April 2017 in Valencia, Spain. Presentations and workshops focussed on advancing the knowledge and skills relating to PCD in: basic science, epidemiology, diagnostic testing, clinical management and clinical trials. The multidisciplinary conference provided an interactive platform for exchanging ideas through a program of lectures, poster presentations, breakout sessions and workshops. Three working groups met to plan consensus statements. Progress with BEAT-PCD projects was shared and new collaborations were fostered. In this report, we summarize the meeting, highlighting developments made during the meeting. Electronic supplementary material The online version of this article (10.1186/s12919-018-0098-9) contains supplementary material, which is available to authorized users.

Up to isomorphism, there are six fixed-point free crystallographic groups in Euclidean 3-space $$\mathbb {E}^3$$E3 generated by twists (screw motions). In each case, an orientable 3-manifold is obtained as the quotient of $$\mathbb {E}^3$$E3 by such a group. The cubic tessellation of $$\mathbb {E}^3$$E3 induces tessellations on each such manifold. The corresponding classification for the 3-torus and the didicosm were classified as `equivelar toroids' and `cubic tessellation of the didicosm' in previous works. This paper concludes the classification of cubic tessellations on the remaining four orientable manifolds.

In this paper we describe a construction for finite abstract chiral 4-polytopes with Schlafli type $$\{3,3,k\}$${3,3,k} (with tetrahedral facets) and with an alternating or symmetric group as automorphism group. We use it to prove that for all but finitely many $$n$$n, both $$A_n$$An and $$S_n$$Sn are the automorphism groups of such a polytope. We also show that the vertex-figures of the polytopes obtained from our construction are chiral.

In this paper, we give an example of a chiral 4-polytope in projective 3-space. This example naturally yields a finite chiral 4-polytope in euclidean 4-space, giving a counterexample to a theorem previously published in the literature [Theorem 11.2 of McMullen (Discrete Comput Geom 32(1):1---35, 2004)].

Up to isomorphism, there is a unique fixed-point-free crystallographic group generated by two (2-fold) twists whose non-intersecting axes have perpendicular directions. Identifying points in E3 which are in the same orbit under the action of this group yields the flat, closed 3-manifold known as the didicosm (also as the Hantzsche-Wendt manifold). When this group is realized as a group of symmetries of the standard cubical tessellation in E3, the resulting quotient gives a cubical tessellation on the didicosm. This paper describes a complete classification of these cubical tessellations on the didicosm into ten classes, according to their automorphism groups.

Among all equivelar vertex-transitive maps on a given closed surface S, the automorphism groups of maps with Schlafli types {3,7} and {7,3} allow the highest possible order. We describe a procedure to transform all such maps into 1- or 2-orbit maps, whose symmetry type has been previously studied. In doing so we provide two procedures to find vertex-transitive maps with Schlafli type {3,7} which are neither regular nor chiral. One of them is by means of operations while the other consists of interpreting them as generalized Cayley maps. We determine all such maps on surfaces with Euler characteristic -1>=@g>=-40.

The paper describes the first known infinite sequence of 2-orbit d-polytopes in \(\mathbb {R}^d\) with \(d \ge 3\). The sequence has the remarkable property that its d-dimensional member has vertex-figures isomorphic to the \((d-1)\)-dimensional member.

Resumen Objetivo Presentar los metodos que se emplean para estudiar la fiabilidad y validez de la cefalometria en 2 dimensiones, los programas y sistemas evaluados, y exponer las medidas y puntos cefalometricos mas conflictivos. Material y metodos Se realizo una revision bibliografica de los estudios publicados sobre trazado digital. Veintiocho articulos cumplieron con los requisitos del estudio, abarcando desde 1981 a 2011. Los elementos estudiados en los articulos son los trazados sobre distintos medios en 2 dimensiones (pelicula radiografica, impresion de copia digital, digitalizador, programas informaticos). Resultados El trazado cefalometrico sobre pelicula radiografica muestra los mejores resultados. La radiografia digital obtenida de telerradiografos digitales actuales o el escaneado en alta resolucion de la pelicula radiografica obtienen los valores mas cercanos al trazado manual, pero fotografiar digitalmente la pelicula presenta diferencias significativas. Conclusiones Los programas informaticos mas modernos son fiables para el estudio cefalometrico en el ambito clinico, y conforme evolucionan recortan diferencias presentes en estudios realizados con programas mas antiguos.

This paper presents the current state of the theory of abstract chiral polytopes together with 39 open problems on this topic.

Graver and Watkins classified edge-transitive maps on closed surfaces into fourteen types. In this note we study these types for maps in orientable and non-orientable surfaces of small genus, including the Euclidean and hyperbolic plane. We revisit both finite and infinite one-ended edge-transitive maps. For the finite ones we give precise description that should enable their enumeration for a given number of edges. Edge-transitive maps on surfaces with small genera are classified in the paper.

A k-orbit map is a map with k flag-orbits under the action of its automorphism group. We give a basic theory of k-orbit maps and classify them up to k⩽4. “Hurwitz-like” upper bounds for the cardinality of the automorphism groups of 2-orbit and 3-orbit maps on surfaces are given. Furthermore, we consider effects of operations like medial and truncation on k-orbit maps and use them in classifying 2-orbit and 3-orbit maps on surfaces of small genus.

In this paper we describe a construction for chiral polytopes with preassigned regular facets. Furthermore we show that this construction implies the existence of chiral d-polytopes, for every rank d≥3.

Schulte classified the discrete chiral polyhedra in Euclidean 3-space and showed that they belong to six families. The polyhedra in three of the families have finite faces and the other three families consist of polyhedra with (infinite) helical faces. We show that all the chiral polyhedra with finite faces are combinatorially chiral. However, the chiral polyhedra with helical faces are combinatorially regular. Moreover, any two such polyhedra with helical faces in the same family are isomorphic.

We say that a (d+1)-polytope P is an extension of a polytope K if the facets or the vertex figures of P are isomorphic to K. The Schläfli symbol of any regular extension of a regular polytope is determined except for its first or last entry. For any regular polytope K we construct regular extensions with any even number as first entry of the Schläfli symbol. These extensions are lattices if K is a lattice. Moreover, using the so-called CPR graphs we provide a more general way of constructing extensions of polytopes.

This paper studies C-group permutation representation graphs, or for short, CPR graphs. C-groups are the groups of abstract regular polytopes. CPR graphs are shown to be a useful tool for studying such polytopes. We establish general properties of CPR graphs. Moreover, we illustrate their use by constructing regular polyhedra with alternating groups An as the automorphism groups.

A regular polyhedron of type $$\{p, q\}$${p,q} has at least 2pq flags, and it is called tight if it has exactly 2pq flags. The values of p and q for which there exist tight orientably regular polyhedra were previously known. We determine for which values of p and q there is a tight non-orientably regular polyhedron of type $$\{p, q\}$${p,q}. Furthermore, we completely classify tight regular polyhedra in terms of their automorphism groups.

We study square-complementary graphs, that is, graphs whose complement and square are isomorphic. We prove several necessary conditions for a graph to be square-complementary, describe ways of building new square-complementary graphs from existing ones, construct infinite families of square-complementary graphs, and characterize square-complementary graphs within various graph classes. The bipartite case turns out to be of particular interest. We also exhibit a square-complementary graph with a triangle, thus answering in the affirmative a question asked independently by Baltic et al. and by Capobianco and Kim. (C) 2014 Elsevier B.V. All rights reserved.

This paper discusses consistent flag bicolorings of maps, in their own right and as generalizations of orientations and pseudo-orientations. Furthermore, a related doubling concept is introduced, and relationships between these ideas are explored.