Loading rate effects on Dog's Bay sand

Anàlisi de la possible influència dels ratis de càrrega i del temps de càrrega total al comportament mecànic de la Dog's Bay Sand, un tipus de sorra carbonatada i sense cimentar de la costa occidental d'Irlanda. S'han dut a terme dos tipus d'assaig: per una banda, assaigs triaxials simples no drenats de compressió; i de manera simultània, assaigs edomètrics. Es conclou que la velocitat de consolidació no influeix de manera significativa i que, en aplicar la càrrega desviadora vertical de compressió, el temps que la mostra està sota la càrrega té més efecte que no la velocitat amb que la mostra és deformada

The product of the split ends gene is required for the maintenance of positional information during Drosophila development

BACKGROUND: The Drosophila split ends (spen) gene encodes a large nuclear protein containing three RNP-type RNA binding motifs, and a conserved transcriptional co-repressor-interacting domain at the C-terminus. Genetic analyses indicate that spen interacts with pathways that regulate the function of Hox proteins, the response to various signaling cascades and cell cycle control. Although spen mutants affect only a small subset of morphological structures in embryos, it has been difficult to find a common theme in spen mutant structural alterations, or in the interactions of spen with known signaling pathways. RESULTS: By generating clones of spen mutant cells in wing imaginal discs, we show that spen function is required for the correct formation and positioning of veins and mechanosensory bristles both on the anterior wing margin and on the notum, and for the maintenance of planar polarity. Wing vein phenotypic alterations are enhanced by mutations in the crinkled (ck) gene, encoding a non-conventional myosin, and correlate with an abnormal spatial expression of Delta, an early marker of vein formation in third instar wing imaginal discs. Positioning defects were also evident in the organization of the embryonic peripheral nervous system, accompanied by abnormal E-Cadherin expression in the epidermis. CONCLUSIONS: The data presented indicate that the role of spen is necessary to maintain the correct positioning of cells within a pre-specified domain throughout development. Its requirement for epithelial planar polarity, its interaction with ck, and the abnormal E-Cadherin expression associated with spen mutations suggest that spen exerts its function by interacting with basic cellular mechanisms required to maintain multicellular organization in metazoans. This role for spen may explain why mutations in this gene interact with the outcome of multiple signaling pathways

Loading rate effects on Dog's Bay sand

Anàlisi de la possible influència dels ratis de càrrega i del temps de càrrega total al comportament mecànic de la Dog's Bay Sand, un tipus de sorra carbonatada i sense cimentar de la costa occidental d'Irlanda. S'han dut a terme dos tipus d'assaig: per una banda, assaigs triaxials simples no drenats de compressió; i de manera simultània, assaigs edomètrics. Es conclou que la velocitat de consolidació no influeix de manera significativa i que, en aplicar la càrrega desviadora vertical de compressió, el temps que la mostra està sota la càrrega té més efecte que no la velocitat amb que la mostra és deformada

Casuística del abdomen agudo y su indicación quirúrgica en un servicio de cirugía. Novedades diagnósticas

Ante la frecuencia del abdomen agudo en la práctica diaria de los equipos de Cirugía de guardia del Servicio de Cirugía General y Digestiva del Hospital de Son Dureta, que representa el 56 % de todas las urgencias que atienden, se revisa la casuística de este amplio concepto diagnóstico comparándola con la de otros autores en especial referencia al llamado abdomen agudo inespecífico que ocupa la mitad de los abdómenes agudos atendidos, señalando las nuevas técnicas diagnósticas como la laparoscopia, la ecografia de alta resolución y los programas informáticos de diagnóstico, con sus limitaciones, subrayando la persistencia de la anamnesis, la exploración física y las exploraciones complementarias como la base de la primera orientación diagnóstica de todo abdomen agudo en vistas a obtener un diagnóstico precoz y una correcta indicación quirúrgica

Analysis of global airline alliances as a strategy for international network development

Thesis (S.M. in Technology and Policy)--Massachusetts Institute of Technology, Engineering Systems Division, Technology and Policy Program; and, (S.M.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2012.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references (p. 117-126).Since the late 1990s, network airlines worldwide have being enrolling in one of the three current Global Airline Alliances (GALs), oneworld, Star Alliance and SkyTeam. By 2011, airlines belonging to the three GALs transported over two-thirds of all international traffic. This thesis studies the reasons that cause an increasing number of airlines to join this collaborative scheme as a way to develop a wider network and to increase profitability by serving international connecting traffic. The evolution of GALs is characterized here by the analysis of the size of these alliances, as well as by the volume of partnerships and code share agreements between alliance partners during the period 2006-2011. The results of this study illustrate the differences between each of the GALs and the degree of dependence of airlines on alliances to develop their international networks. By most indicators, the largest alliance, Star Alliance, is the GAL in which member airlines rely more on their alliance partners when developing code share agreements with foreign airlines. In all three GALs, code share agreements between alliance partners are much less likely to be broken than with nonpartner airlines. Airlines operating in the transatlantic markets appear to be the most advanced firms in the marketing of code shared itineraries. The empirical analysis is complemented with a review of the theoretical benefits of GALs to airlines, alternative network models for international growth, the impact of alliances on customers' welfare, their potential anti-competitive effects on independent carriers, and the current regulatory framework affecting alliances on both sides of the North Atlantic. Overall, this work provides a holistic view of the GALs as a model for network development, to describe their policy implications, and to suggest key drivers in the future of airlines' network development strategies.by Antonio Tugores-García.S.M.S.M.in Technology and Polic

A single promoter directs both housekeeping and erythroid preferential expression of the human ferrochelatase gene.

We have isolated and characterized the 5'-flanking region of the gene for human ferrochelatase (HFC), the last enzyme of the heme biosynthetic pathway. The proximal promoter of the gene is contained within a region that structurally resembles a CpG island and is devoid of general cis elements such as TATA and CAAT boxes. Recognition sites for the ubiquitous Sp1 family of transcription factors, as well as for the erythroid-specific trans-acting factors NF-E2 and GATA-1 were found, and binding of regulatory proteins to these elements was analyzed by in vitro DNase I protection assays. The contribution of the various cis elements to both ubiquitous and erythroid preferential expression of the HFC gene was assessed by using transient transfection assays. These showed that a minimal Sp1-driven promoter devoid of the upstream erythroid-specific elements was sufficient for erythroid preferential expression of the HFC gene. However, elimination of a repressor sequence lying between the minimal promoter and the erythroid-specific elements resulted in high levels of expression in human erythroleukemic K562 cells only when the cis elements recognized by GATA-1 and NF-E2 were present, suggesting that the activity of these factors is regulated by a downstream repressor in erythroid cells

Ets homologous factor (EHF) has critical roles in epithelial dysfunction in airway disease

The airway epithelium forms a barrier between the internal and external environments. Epithelial dysfunction is critical in the pathology of many respiratory diseases, including cystic fibrosis. Ets homologous factor (EHF) is a key member of the transcription factor network that regulates gene expression in the airway epithelium in response to endogenous and exogenous stimuli. EHF , which has altered expression in inflammatory states, maps to the 5' end of an intergenic region on Chr11p13 that is implicated as a modifier of cystic fibrosis airway disease. Here we determine the functions of EHF in primary human bronchial epithelial (HBE) cells and relevant airway cell lines. Using EHF ChIP followed by deep sequencing (ChIP-seq) and RNA sequencing after EHF depletion, we show that EHF targets in HBE cells are enriched for genes involved in inflammation and wound repair. Furthermore, changes in gene expression impact cell phenotype because EHF depletion alters epithelial secretion of a neutrophil chemokine and slows wound closure in HBE cells. EHF activates expression of the SAM pointed domain-containing ETS transcription factor, which contributes to goblet cell hyperplasia. Our data reveal a critical role for EHF in regulating epithelial function in lung disease

Age, Origin and Functional Study of the Prevalent LDLR Mutation Causing Familial Hypercholesterolaemia in Gran Canaria

The p.(Tyr400_Phe402del) mutation in the LDL receptor (LDLR) gene is the most frequent cause of familial hypercholesterolaemia (FH) in Gran Canaria. The aim of this study was to determine the age and origin of this prevalent founder mutation and to explore its functional consequences. For this purpose, we obtained the haplotypic information of 14 microsatellite loci surrounding the mutation in one homozygous individual and 11 unrelated heterozygous family trios. Eight different mutation carrier haplotypes were identified, which were estimated to originate from a common ancestral haplotype 387 (110–1572) years ago. This estimation suggests that this mutation happened after the Spanish colonisation of the Canary Islands, which took place during the fifteenth century. Comprehensive functional studies of this mutation showed that the expressed LDL receptor was retained in the endoplasmic reticulum, preventing its migration to the cell surface, thus allowing us to classify this LDLR mutation as a class 2a, defective, pathogenic variant.This work was supported by grants from the Instituto de Salud Carlos III (ISCIII): PI20/00846, INT21/00032 (RMS), CM19/00116 (AMGL) with the participation of the European Union through European Regional Development Funds (“A way to make Europe”), the Fundación Canaria del Instituto de Investigaciones Sanitarias de Canarias (FCIISC): PIFIISC20/16 and the Fundación Mapfre Guanarteme (Beca Investigación 2020). NMS was supported by a María Zambrano Fellowship funded by the Spanish Ministry of Universities within the “Next Generation EU” scheme

Age, Origin and Functional Study of the Prevalent LDLR Mutation Causing Familial Hypercholesterolaemia in Gran Canaria

The p.(Tyr400_Phe402del) mutation in the LDL receptor (LDLR) gene is the most frequent cause of familial hypercholesterolaemia (FH) in Gran Canaria. The aim of this study was to determine the age and origin of this prevalent founder mutation and to explore its functional consequences. For this purpose, we obtained the haplotypic information of 14 microsatellite loci surrounding the mutation in one homozygous individual and 11 unrelated heterozygous family trios. Eight different mutation carrier haplotypes were identified, which were estimated to originate from a common ancestral haplotype 387 (110-1572) years ago. This estimation suggests that this mutation happened after the Spanish colonisation of the Canary Islands, which took place during the fifteenth century. Comprehensive functional studies of this mutation showed that the expressed LDL receptor was retained in the endoplasmic reticulum, preventing its migration to the cell surface, thus allowing us to classify this LDLR mutation as a class 2a, defective, pathogenic variant.This work was supported by grants from the Instituto de Salud Carlos III (ISCIII): PI20/00846, INT21/00032 (RMS), CM19/00116 (AMGL) with the participation of the European Union through European Regional Development Funds (“A way to make Europe”), the Fundación Canaria del Instituto de Investigaciones Sanitarias de Canarias (FCIISC): PIFIISC20/16 and the Fundación Mapfre Guanarteme (Beca Investigación 2020). NMS was supported by a María Zambrano Fellowship funded by the Spanish Ministry of Universities within the “Next Generation EU” scheme.Peer reviewe