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No / The epidermal differentiation program is regulated at several levels including signaling pathways, lineage-specific transcription factors, and epigenetic regulators that establish well-coordinated process of terminal differentiation resulting in formation of the epidermal barrier. The epigenetic regulatory machinery operates at several levels including modulation of covalent DNA/histone modifications, as well as through higher-order chromatin remodeling to establish long-range topological interactions between the genes and their enhancer elements. Epigenetic regulators exhibit both activating and repressive effects on chromatin in keratinocytes (KCs): whereas some of them promote terminal differentiation, the others stimulate proliferation of progenitor cells, as well as inhibit premature activation of terminal differentiation-associated genes. Transcription factor-regulated and epigenetic mechanisms are highly connected, and the p63 transcription factor has an important role in the higher-order chromatin remodeling of the KC-specific gene loci via direct control of the genome organizer Satb1 and ATP-dependent chromatin remodeler Brg1. However, additional efforts are required to fully understand the complexity of interactions between distinct transcription factors and epigenetic regulators in the control of KC differentiation. Further understanding of these interactions and their alterations in different pathological skin conditions will help to progress toward the development of novel approaches for the treatment of skin disorders by targeting epigenetic regulators and modulating chromatin organization in KCs. / National Alopecia Areata Foundation; (R13AR067088-01) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases; and the National Center for Advancing Translational Sciences

A Ceratoconjuntivite Seca (KCS Keratoconjunctivitis Sicca) é uma desordem imunomediada e resulta de alterações do componente aquoso do filme lacrimal e da deficiência dos componentes lipídicos e mucoso.Seu diagnóstico é baseado no Teste Lacrimal de Schirmer (TLS) e no Teste de Ruptura do Filme Lacrimal (TRFL) e tem como sinais clínicos: secreção mucopurulenta, hiperemia conjuntival, blefaroespasmos, fotofobia, incômodo, dor, vascularização, opacidade corneana e pigmentação, além de cegueira em casos avançados. O tratamento convencional consiste em aplicações diárias de Ciclosporina 0,2% ou Tacrolimus 0,03% (pomada ou colírio oftálmicos), que apesar de controlar a doença, são custosos, não curativos e exigem alto comprometimento da interação paciente-proprietário. A terapia celular usando células-tronco (CT) traz uma nova esperança para doenças sem tratamento efetivo. Neste trabalho utilizamos CT mesenquimais (CTM) obtidas a partir de membrana amniótica (CTMA) de cães obtidas a partir do descarte destes tecidos em campanhas de castrações em diferentes tempos gestacionais, sem formação tumoral quando submetidas ao teste tumorigênico durante 60 dias. Dois animais com KCS crônica foram tratados com duas injeções de CTMA com intervalo de 30 dias, sendo a primeira de 0,5x106 células e a segunda de 1x106 células em cada glândula. Na segunda semana após a terapia foi observado aumento da TLS sugerindo um benéficio da terapia que foi diminuindo com o passar das semanas. O TRFL oscilou durante os testes e não apresentou diferenças significativas. A terapia celular utilizando CTMA de cães melhorou a condição ocular nos dois casos em momentos e parâmetros variados, com repercussão na melhoria da superfície, mas não houve regressão do quadro clínico. Investigações futuras em estágios menos avançados da doença podem ajudar a elucidar os mecanismos pelos quais esse efeito foi obtido / Keratoconjunctivitis Sicca (KCS) is an immune-mediated disorder and results from changes in the aqueous component of the tear film and also from the impairment of lipid and mucous components. Diagnosis is based on Lacrimal Schirmer Test (LST) and Tear Film Break Test (TFBT) and its clinical signs: purulent discharge, conjunctival hyperemia, blefaroespasmos, photophobia, discomfort, pain, vascularization, corneal opacity and pigmentation, addition of blindness in advanced cases. The standard treatment consists of daily applications of 0.2% cyclosporin or tacrolimus 0.03% (ophthalmic ointment or drops), that in spite of controlling the disease are expensive, require the patient does not curative and and require greater involvement of the patient-owner interaction. Cell therapy using stem cells (SC) brings new hope for diseases without effective treatment. In this work we used CT mesenchymal cells (MSCs) obtained from dogs amniotic membrane (AMSC) in the capanhas of castration at different times gestacionai without tumor formation tumorigenic when subjected to the test during 60 days. Two animals with chronic KCS were treated with two injections of CTMA with 30-day intervals, the first of which 0,5x106 cells and the second of 1x106 cells in each gland. In the second week after therapy was an increase in LST that has been decreasing over the weeks. The BTTF fluctuated during testing and no significant differences. Cell therapy using AMSC dogs improved the eye condition in both cases at times and different parameters, with consequent improvement in ocular surface but there was no regression of the clinical picture. Future research in less advanced stages of the disease may help to elucidate the mechanisms by which this effect was obtained

A Ceratoconjuntivite Seca (KCS Keratoconjunctivitis Sicca) é uma desordem imunomediada e resulta de alterações do componente aquoso do filme lacrimal e da deficiência dos componentes lipídicos e mucoso.Seu diagnóstico é baseado no Teste Lacrimal de Schirmer (TLS) e no Teste de Ruptura do Filme Lacrimal (TRFL) e tem como sinais clínicos: secreção mucopurulenta, hiperemia conjuntival, blefaroespasmos, fotofobia, incômodo, dor, vascularização, opacidade corneana e pigmentação, além de cegueira em casos avançados. O tratamento convencional consiste em aplicações diárias de Ciclosporina 0,2% ou Tacrolimus 0,03% (pomada ou colírio oftálmicos), que apesar de controlar a doença, são custosos, não curativos e exigem alto comprometimento da interação paciente-proprietário. A terapia celular usando células-tronco (CT) traz uma nova esperança para doenças sem tratamento efetivo. Neste trabalho utilizamos CT mesenquimais (CTM) obtidas a partir de membrana amniótica (CTMA) de cães obtidas a partir do descarte destes tecidos em campanhas de castrações em diferentes tempos gestacionais, sem formação tumoral quando submetidas ao teste tumorigênico durante 60 dias. Dois animais com KCS crônica foram tratados com duas injeções de CTMA com intervalo de 30 dias, sendo a primeira de 0,5x106 células e a segunda de 1x106 células em cada glândula. Na segunda semana após a terapia foi observado aumento da TLS sugerindo um benéficio da terapia que foi diminuindo com o passar das semanas. O TRFL oscilou durante os testes e não apresentou diferenças significativas. A terapia celular utilizando CTMA de cães melhorou a condição ocular nos dois casos em momentos e parâmetros variados, com repercussão na melhoria da superfície, mas não houve regressão do quadro clínico. Investigações futuras em estágios menos avançados da doença podem ajudar a elucidar os mecanismos pelos quais esse efeito foi obtido / Keratoconjunctivitis Sicca (KCS) is an immune-mediated disorder and results from changes in the aqueous component of the tear film and also from the impairment of lipid and mucous components. Diagnosis is based on Lacrimal Schirmer Test (LST) and Tear Film Break Test (TFBT) and its clinical signs: purulent discharge, conjunctival hyperemia, blefaroespasmos, photophobia, discomfort, pain, vascularization, corneal opacity and pigmentation, addition of blindness in advanced cases. The standard treatment consists of daily applications of 0.2% cyclosporin or tacrolimus 0.03% (ophthalmic ointment or drops), that in spite of controlling the disease are expensive, require the patient does not curative and and require greater involvement of the patient-owner interaction. Cell therapy using stem cells (SC) brings new hope for diseases without effective treatment. In this work we used CT mesenchymal cells (MSCs) obtained from dogs amniotic membrane (AMSC) in the capanhas of castration at different times gestacionai without tumor formation tumorigenic when subjected to the test during 60 days. Two animals with chronic KCS were treated with two injections of CTMA with 30-day intervals, the first of which 0,5x106 cells and the second of 1x106 cells in each gland. In the second week after therapy was an increase in LST that has been decreasing over the weeks. The BTTF fluctuated during testing and no significant differences. Cell therapy using AMSC dogs improved the eye condition in both cases at times and different parameters, with consequent improvement in ocular surface but there was no regression of the clinical picture. Future research in less advanced stages of the disease may help to elucidate the mechanisms by which this effect was obtained

Surge Free Added Resistance testing in variable head wave conditions were completed for a container ship model. The added resistance experiments include calm water, head wave, and oblique wave cases with a focus on establishing a validation benchmark for CFD codes computing the added resistance and motions of the ship model during maneuvering. The ship used is a 1/85.19 scale KRISO Container Ship, KCS, model with a length of 2.70 m. Tests were performed at the IIHR wave basin. The 20 x 40 x 4.5 m wave basin is equipped with 6 inline plunger type wave makers and a 3 degrees of freedom carriage. A 4 degrees of freedom, surge, heave, roll, and pitch free mount with a mass spring damper system was used to tow the model. Calm water tests were performed for 13 Froude numbers between 0.0867 and 0.2817. The resistance coefficients, sinkage, and trim were found for each test. The calm water results were obtained and compared to results from towing tank facilities, with traditional mounts, to estimate facility biases at the IIHR wave basin. The results show that the size difference of the IIHR model and surge free motion create magnitude differences between facilities. Head and oblique wave tests were performed at Froude number 0.26 and wave height to wavelength ratio, H/λ, of 0.0167. For all wave tests, time histories of wave amplitude, resistance, and 4 DOF were measured. Fourier analysis was completed for all time histories of waves, forces, and motions and the 0th, 1st, and 2nd harmonic amplitudes and phases are presented. All head wave results are compared to other facilities data taken in a towing tank with a traditional mount. The data from all wave heading data was analyzed with a focus on the trends with incremented wave encounter angle. Most harmonic amplitudes show good agreement between all facilities, but removal of the small model used by IIHR shows even better agreement between facilities. The oblique wave heading data shows good agreement with the only other experimental oblique wave added resistance testing. Complete uncertainty analysis was completed for select cases for calm water, head wave, and oblique wave conditions. The uncertainty showed accurate data form most wavelength settings.

The capability of CFD is assessed by utilizing CFDShip-Iowa V4.5 for the prediction of the 6DOF motion responses, forces, moments and the local flow field of the 2.7m KCS model in various weather/operating conditions. The discretized propeller is preferred and the rudder is designed to be active up to ±35 degrees. Grid triplets are generated with the refinement ratio √2 and verification is achieved for the resistance and propeller open water tests while for the other tests is only partially fulfilled. The verification shows unsmooth convergence, however, the errors from grid triplets are small. The propeller open water test validates the performance of the discretized propeller successfully. The free decay tests could predict reasonable heave/pitch/roll natural frequencies. The resistance test verifies the nominal wake distribution. The self-propulsion test using discretized propeller shows 18% higher propeller inflow and 0.1 thrust deduction factor compared to resistance test. A propeller blade that sweeps the starboard experienced higher thrust inducing non-axisymmetric propeller wake and thus affecting the angle of attack of the rudder. Neutral rudder angle diminishes effective angle of attack and keeps the course straight. Maneuvering simulations could predict qualitatively good agreement for validation variables while the trajectory needs more improvement. Using the discretized propeller for the head/oblique wave course-keeping simulations achieved validation successfully. The RAO of added thrust, torque and propeller rotational speed resembles the RAO of added-resistance except showing larger values during long waves. The mean propeller efficiency is at the minimum when the ship experiences a resonance. The first harmonic amplitude of the propeller efficiency increases followed by the increase of the wavelength.

Kingdom center Sweden is a small-town Pentecostal community located in the Swedish province of Scania. What, on a surface level, distinguishes this community from other Christian communities in Sweden is that the congregation operates a cowboy-themed wilderness center. Religious communities that operate businesses is not in itself a novel occurrence; instead, it is the cowboy theme in particular that potentially alludes to a phenomenon, novel to a Swedish context, that is, cowboy Christianity. Thus, this essay centers on examining if and how the congregation can be understood as a representation of cowboy Christianity in Sweden. In addition to this, a theological reading is performed in order to further examine the roots of the congregation. The results of the examination suggest that Kingdom Center Sweden, outwardly, shares characteristics with other movements within the cowboy Christian milieu; this, based on images in the congregation’s e-book and on their YouTube accounts in which members of the congregation both dress in cowboy-themed clothes when appearing as a congregation, and to some extent has appropriated practices such as baptism in a horse through and wedding services on horseback – all of which has been previously connected to the cowboy Christian phenomena. Moreover, the information on their YouTube account and e-book brings out how the congregation promotes itself as existing within a cowboy Christian milieu, which consists of cowboy churches, rodeo ministries and profiles within the Christian cowboy community. However, the analysis of the theological material suggests that this, seemingly isolated case of Cowboy Christianity in Sweden, is not merely the result of cowboy Christianity mushrooming from the Great Plains to rural Scania. Instead, the examined material suggests that, theologically, the movement kept it ties with the prosperity theology associated with faith movements and the Swedish Word of Life. Thus, suggesting that after the congregation was excluded from the Swedish faith community, they appropriated the material culture and traits of the cowboy Christian phenomena. Hence, rooting the congregation in another contemporary offshoot of Christianity.

Although the capability of computational fluid dynamics (CFD) in modeling ship hydrodynamics is well explored in many studies, they still have two main limitations. First, those studies ignore the effect of non-uniform shear current which exists in realistic situation. Second, the focus of most studies was laid more on the seakeeping/maneuvering performance and less attention was paid to survivability of ships due to extreme ship response events in waves, which are considered rare events but influential. In this thesis, we explore the capability of CFD in those two areas. In the first part of the thesis, the hydrodynamic performance of KCS in the presence of a non-uniform shear current is investigated for the first time using high-fidelity CFD simulations. Various shear current conditions with different directions were considered and results were compared with the ones with no shear current. The second part of the thesis focuses on study of rare events of ship responses by development of extreme response conditioning techniques to design the wave trail. Two conditioned techniques based on Gaussian and non-Gaussian processes are considered.

Le besoin de compétitivité impose aujourd'hui de concevoir plus rapidement, mieux et moins cher que les concurrents. Dans ce contexte, la prise en compte de l'ensemble des contraintes du produit dépends du retour des indicateurs de performance (coût, risque, qualité, délai,...). Il est donc important de bien évaluer ces indicateurs afin de retourner des informations robustes et cohérentes qui permettent de prendre une bonne décision pour piloter le cycle de développement du produit de sort qu'on obtient un meilleur rapport qualité/coût. L'interopérabilité des approches QFD, FMEA et KCs a été étudiée afin de les exploiter dans un seul cadre de maîtrise de la qualité pour assurer l'homogénéité et la cohérence des indicateurs de la qualité. Le coût a été pris en compte en proposant l'approche CbFMEA, basée sur FMEA classique, qui permet d'estimer le coût de non-qualité afin d'évaluer la gravité financière des défaillances du produit. Ce coût a été ajouté au coût de fabrication du produit estimé par la méthode ABC. L'approche du coût (CbFMEA/ABC) a été couplée à l'approche de la qualité (QFD/FMEA/KCs) résultant une approche conjointe qualité/coût illustrée par un diagramme d'activités. Un modèle de données de l'approche conjointe qualité/coût a été proposé est une maquette informatique a été développée afin de valider les concepts et le modèle proposés. Une application de cette approche a été illustrée dans la phase de pré-gamme d'usinage via un cas d'études. Cette application est nommée QCCPP, elle fournit des indicateurs de capabilité, de risques et du coût. L'objectif est l'aide à la décision lors du choix multicritères des ressources d'usinage pour l'amélioration conjointe de rapport qualité/coût du produit.