Academic literature on the topic 'Skin pattern initiation model'

We have previously demonstrated intra- and extra-cellular factors that govern somatic evolution of the malignant phenotype can be modeled through evolutionary game theory, a mathematical approach that analyzes phenotypic adaptation to in-vivo environmental selection forces. Here we examine the global evolutionary dynamics that control evolutionary dynamics explicitly addressing conflicting data and hypothesis regarding the relative importance of the mutator phenotype and microenvironment controls. We find evolution of invasive cancer follows a biphasic pattern. The first phase occurs within normal tissue, which possesses a remarkable adaptive landscape that permits non-competitive coexistence of multiple cellular populations but renders it vulnerable to invasion. When random genetic mutations produce a fitter phenotype, self-limited clonal expansion is observed — equivalent to a polyp or nevus. This step corresponds to tumor initiation in classical skin carcinogenesis experiments because the mutant population deforms the adaptive landscape resulting in the emergence of unoccupied fitness peaks — a premalignant configuration because, over time, extant cellular populations will tend to evolve toward available fitness maxima forming an invasive cancer. We demonstrate that this phase is governed by intracellular processes, such as the mutation rate, that promote phenotypic diversity and environmental factors that control cellular selection and population growth. These results provide an integrative model of carcinogenesis that incorporates cell-centric approaches such as the mutator phenotype hypothesis with the critical role of the environmental demonstrated by Bissell and others. The biphasic dynamics of carcinogenesis give a quantitative framework of understanding for the empirically observed initiation and promotion/progression stages in skin carcinogenesis experimental models.

Leukemias are the most common pediatric malignancies diagnosed in western industrialized societies. In spite of the substantial incidence of childhood leukemia in the United States and other countries, neither epidemiology studies conducted in human populations nor hazard identification studies conducted using traditional animal models have identified environmental or other factors that are directly linked to increased risk of disease. Molecular biology data and mathematical modeling of incidence patterns suggest that pediatric leukemogenesis may occur through a multistage or “multihit” mechanism that involves both in utero and postnatal events. The authors propose that pediatric leukemias can be modeled experimentally using a “multihit” paradigm analogous to the “initiation-promotion” and “complete carcinogenesis” models developed for tumor induction in mouse skin and rat liver. In this model for childhood leukemia, an initial genetic alteration occurs during in utero or early postnatal development, but clinical disease develops only upon additional genetic or nongenetic events that occur during the postnatal period. Application of this multistage or “multihit” model to hazard assessment studies conducted in transgenic or knockout mice carrying relevant molecular lesions may provide a sensitive approach to the identification of environmental agents that are important risk factors for childhood leukemia.

ABSTRACTThe polyomavirus tumor (T) antigens play crucial roles in viral replication, transcription, and cellular transformation. They are encoded by partially overlapping open reading frames (ORFs) located in the early region through alternative mRNA splicing. The T expression pattern of the trichodysplasia spinulosa-associated polyomavirus (TSPyV) has not been established yet, hampering further study of its pathogenic mechanisms and taxonomic relationship. Here, we characterized TSPyV T antigen expression in human cell lines transfected with the TSPyV early region. Sequencing of T antigen-encoded reverse transcription-PCR (RT-PCR) products revealed three splice donor and acceptor sites creating six mRNA splice products that potentially encode the antigens small T (ST), middle T (MT), large T (LT), tiny T, 21kT, and alternative T (ALTO). Except for 21kT, these splice products were also detected in skin of TSPyV-infected patients. At least three splice products were confirmed by Northern blotting, likely encoding LT, MT, ST, 21kT, and ALTO. Protein expression was demonstrated for LT, ALTO, and possibly MT, with LT detected in the nucleus and ALTO in the cytoplasm of transfected cells. Splice site and start codon mutations indicated that ALTO is encoded by the same splice product that encodes LT and uses internal start codons for initiation. The genuineness of ALTO was indicated by the identification of acetylated N-terminal ALTO peptides by mass spectrometry. Summarizing, TSPyV exhibits an expression pattern characterized by both MT and ALTO expression, combining features of rodent and human polyomaviruses. This unique expression pattern provides important leads for further study of polyomavirus-related disease and for an understanding of polyomavirus evolution.IMPORTANCEThe human trichodysplasia spinulosa-associated polyomavirus (TSPyV) is distinguished among polyomaviruses for combining productive infection with cell-transforming properties. In the research presented here, we further substantiate this unique position by indicating expression of both middle T antigen (MT) and alternative T antigen (ALTO) in TSPyV. So far, none of the human polyomaviruses was shown to express MT, which is considered the most important viral oncoprotein of rodent polyomaviruses. Coexpression of ALTO and MT, which involves a conserved, recently recognized overlapping ORF subject to positive selection, has not been observed before for any polyomavirus. As a result of our findings, this study provides valuable new insights into polyomavirus T gene use and expression. Obviously, these insights will be instrumental in further study and gaining an understanding of TSPyV pathogenicity. More importantly, however, they provide important leads with regard to the interrelationship, functionality, and evolution of polyomaviruses as a whole, indicating that TSPyV is a suitable model virus to study these entities further.

Abstract Chronic Graft Versus Host Disease (CGVHD) remains the main source of non-relapse mortality and morbidity among recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although our lab and others have identified infiltrates of Th1/Tc1 and Th17 effectors in skin and oral mucosa, CGVHD targets multiple organs and no common factor or pathway has been demonstrated to reflect the broad range of CGVHD inflammatory and fibrotic manifestations. To identify the systemic cytokine pathways supporting the development and persistence of CGVHD, we chose to profile gene expression in circulating monocytes; monocytes up-regulate distinct patterns of gene expression in response to different cytokines, acting as in situ reporters. The NIH Natural History Study of CGVHD (NCT00092235) has primarily enrolled moderate to severely affected patients. Microarray analysis was performed on sorted monocytes from 10 normal controls (ND) and 26 patients selected from this cohort based on severe cutaneous involvement. Two interrelated pathways, each containing multiple genes, were consistently up-regulated across a cutaneous CGHVD spectrum ranging from lichenoid infiltrates to extensive sclerosis: (1) Interferon (IFN)-inducible genes including those involved in signaling, lymphocyte homeostasis and trafficking, apoptosis and antigen uptake and presentation (STAT1, CXCL10, TNFSF13B, TNFSF10, TAP1), and (2) innate immune receptors for pathogens and cellular damage that can trigger IFN production and inflammasome assembly (TLR2, TLR4, TLR7, AIM2, DDX58, CLEC4E). Using multiplex RNA gene expression assays (Nanostring) to verify these pathways, we found significant up-regulation of IFN-inducible and damage-response genes in 69 CGVHD patients with a broad range of organ involvement, as compared with 14 allo-HSCT patients never developing CGVHD, or with 19 normal controls (Figure 1A, B). These pathways were further substantiated in plasma ELISA assays showing elevated levels of IFN-induced chemokines (CXCL9, CXCL10) in both lichenoid and severe sclerotic patients. Immunohistochemistry substantiated expression of Type I IFN-induced factors (MxA) in inflammatory infiltrates in CGVHD-targeted organs: lichenoid and sclerotic skin, oral mucosa and salivary gland. Consistent with induction of Type I IFN by activation of TLR and RIG-I receptors, levels of expression of DDX58 and TLR7 correlated with up-regulation of Type I IFN inducible genes (OAS1, IFIT1, XAF1). Finally, multiplex RNA assessments on monocytes collected from 18 patients over serial time courses following NCI allo-HSCT protocols (NCT00520130 and NCT00074490) substantiated a pattern of parallel up-regulation of multiple IFN-inducible and damage responsive genes at CGVHD onset, and of decline upon therapy and resolution (Figure 1C). A key point is that comparable up-regulation of these pathways was found in patients with extensive lichenoid or sclerotic CGVHD, both in the established CGVHD patients in the initial microarray and in the serial time courses of CGVHD development. These results support a model that IFN and inflammasome activation induced by the innate immune systemÕs response to damage initiates an inflammatory process in CGVHD; IFN then can induce damage receptors, chemokines, cytokines and enhanced antigen presentation that sustain CGVHD. These interlocking analyses of gene expression patterns, plasma analytes and tissue are the first to support a unifying hypothesis of induction of IFN by innate response to cellular damage as a mechanism for initiation and persistence of CGVHD. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

The extrauterine development of marsupial pouch young (northern brown bandicoot Isoodon macrourus) has facilitated the study of the effects of murine epidermal growth factor (mEGF) on pattern formation in skin. Hair follicle initiation and development, which in the mouse would occur from about Days 13–14 of gestation onward, occurs postnatally. In the present study the effect in vivo of mEGF on developing skin corresponding to mouse gestational ages from Day 13 onward was examined. Subcutaneous injections of mEGF (0· 5, 1 ·0 and 2· 0 µg g-1 body weight) or equivalent volumes of saline (0· 9% w/w) were administered daily, before and during hair follicle initiation and development. Murine EGF inhibited the formation of hair follicles, hair follicle sweat glands, sebaceous glands and dermal papillae. The pattern of follicle initiation was perturbed. The characteristic trio follicle grouping was absent, and follicle rudiment densities (no. per mm2skin surface) were significantly lower in animals treated with mEGF, whereas follicle diameters were increased. These data may reflect a role for the epidermal growth factor (EGF) receptor in epidermal pattern formation. The EGF receptor and its potential ligands (such as EGF, transforming growth factor (TGF-α) or other yet-to-be-discovered ligands) perhaps act as parts of a pattern-forming system in vertebrate skin. Extra keyword: EGF receptor.

The poem compares Odysseus with Heracles through shared epithets and exploits (including catabasis and archery), but the Heracles paradigm is discredited by Heracles’ murder of his guest-friend Iphitus. The vignette of Odysseus’ naming by his grandfather, Autolycus, identifies the source of the hero’s ancestral cunning and motivates his visit as a young man to Parnassus, where he kills a boar when hunting with his uncles, thereby effecting his initiation into adulthood. The boar hunt test is the pattern for the bow contest: Odysseus corresponds in each to the marginalized initiation candidate. The lightly armed Odysseus who, like Apollo, kills young men with his arrows gives way in the fight with the suitors to a heavily armed hoplite figure whose divine model is Apollo Delphinios, who at the new moon of the new year presides over the ἀπέλλα‎ (assembly) where young men make the transition into the community of adult men.

TOWARDS THE NEW LIFE Theology and Importance of Christian Initiation for the Life of Faith The book is in equal parts a presentation and an invitation. The subject matter of both is the mystagogical initiation leading to the personal encounter with God and eventually to the union within the Church in Christ, which happens initially and particualry in the sacramental liturgy. Mystagogy was the essential experience of life in the early Church and now is being so intensely discussed and postulated by the ecclesial Magisterium and through the teaching of the recent popes and synods. Within the ten chapters of this book the reader proceeds through the aspects strictly associated with Christian initiation, noticeable in catechumenate and suggestive for further Christian life. It is not surprising then, that the study begins with answering the question about the sense of dealing with catechumenate at all. The response developed in the first chapter covers four key points: the contemporary state of our faith, the need for dialogue in evangelization, the importance of liturgy in the renewal of faith and the obvious requirement of follo- wing the Church’s Magisterium, quite explicit in the subject undertaken within this book. The introductory chapter is meant to evoke interest in catechumenate as such and encourage comprehension of its essence, in order to keep it in mind while planning contemporary evangelization. For doing this with success and avoiding pastoral archeology, we need a competent insight into the main message and goal of Christian initiation. Catechumenate is the first and most venerable model of formation and growth in faith and therefore worth knowing. The second chapter tries to cope with the reasons and ways of the present return to the sources of catechumenate with respect to Christian initiation understood to be the building of the relationship with God. The example of catechumenate helps us to discover, how to learn wisely from the history. This would definitely mean to keep the structure and liturgy of catechumenate as a vehicle of God’s message, which must be interpreted and adapted always anew and with careful and intelligent consideration of the historical flavour on particular stages within the history of salvation and cultural conditions of the recipients. For that reason we refer to the Biblical resources and to the historical examples of catechumenate including its flourishing and declining periods, after which we are slowly approaching the present reinterpretation of the catechumenal process enhanced by the official teaching of the Church. As the result of the latter, particularly owing to the Vatican Council II, we are now dealing with the renewed liturgy of baptism displayed in two liturgical books: The Rite of Baptism for Children and the Rite of Christian Initiation of Adults (RCIA). This version for adults is the subjectmatter of the whole chapter, in which a reader can find theological analyses of the particular rites as well as numerous indications for improving one’s life with Christ in the Church. You can find interesting associations among the rites of initiation themselves and astounding coherence between those rites and the sacraments of the Eucharist, penance and other sacraments, which simply means the ordinary life of faith. Deep and convincing theology of the process of initiation proves the inspiring spiritual power of the initial and constitutive sacraments of baptism and confirmation, which may seem attractive not only for catechumens but also for the faithful baptized in their infancy, and even more, since they might have not yet had a chance to see what a plausible treasure they have been conveying in their baptismal personality. How much challenge for further and constant realization in life may offer these introductory events of Christian initiation, yet not sufficiently appreciated by those who have already been baptized and confirmed! We all should submit to permanent re-evangelization according to this primary pattern, which always remains essential and fundamental. Very typical and very post-conciliar approach to Christian formation appears in the communal dimension, which guards and guarantees the ecclesial profile of initiation and prepares a person to be a living member of the Church. The sixth chapter of the book is dealing with ecclesial issues in liturgy. They refer to comprehending the word of God, especially in the context of liturgy, which brings about a peculiar theological sense to it and giving a special character to proclaiming the Gospel, which the Pope Francis calls “liturgical proclamation”. The ecclesial premises influence the responsibility for the fact of accompanying the candidates, who aim at becoming Christ’s disciples. As the Church is teaching also in the theological and pastoral introduction to the RCIA, this is the duty of all Christians, which means: priests, religious and the lay, because the Church is one organism in whose womb the new members are conceived and raised. As this fact is strongly claimed by the Church the method of initiation arises to great importance. The seventh chapter is dedicated to the analysis of the catechumenal method stemming from Christ’s pedagogy and His mystery of Incarnation introducing a very important issue of implementing the Divine into the human. The chapter concerning this method opens a more practical part of the book. The crucial message of it is to make mystagogy a natural and obvious method which is the way of building bonds with Christ in the community of the people who already have these bonds and who are eager to tighten them and are aware of the beauty and necessity of closeness with Christ. Christian initiation is the process of entering the Kingdom of God and meeting Christ up to the union with Him – not so much learning dogmas and moral requirements. This is a special time when candidates-catechumens-elected mature in love and in their attitude to Christ and people, which results in prayer and new way of life. As in the past catechumenate nowadays inspires the faithful in their imagination of love and mercy as well as reminds us about various important details of the paschal way of life, which constitute our baptismal vocation, but may be forgotten and now with the help of catechumenate can be recognized anew, while accompanying adults on their catechumenal way. The book is meant for those who are already involved in catechumenal process and are responsible for the rites and formation as well as for those who are interested in what the Church is offering to all who consciously decide to know and follow Christ. You can learn from this book, what is the nature and specificity of the method suggested by the Rite itself for guiding people to God the Saviour and to the community of His people. The aim of the study is to present the universal way of evangelization, which was suggested and revealed by God in His pedagogy, particularly through Jesus Christ and smoothly adopted by the early Church. This way, which can be called a method, is so complete, substantial and clear that it deserves rediscovery, description and promotion, which has already started in the Church’s teaching by making direct references to such categories as: initiation, catechumenate, liturgical formation, the rereading the Mystery of Christ, the living participation in the Mystery and faith nourished by the Mystery. The most engaging point with Christian initiation is the fact, that this seems to be the most effective way of reviving the parish, taking place on the solid and safe ground of liturgy with the most convincing and objective fact that is our baptism and our new identity born in baptismal regenerating bath. On the grounds of our personal relationship with God and our Christian vocation we can become active apostles of Christ. Evangelization begins with ourselves and in our hearts. Thinking about the Church’s mission, we should have in mind our personal mission within the Church and we should refer to it’s roots – first to our immersion into Christ’s death and resurrection and to the anointment with the Holy Spirit. In this Spirit we have all been sent to follow Christ wherever He goes, not necessarily where we would like to direct our steps, but He would. Let us cling to Him and follow Him! Together with the constantly transforming and growing Church! Towards the new life!

This chapter introduces an in vitro model as a means of studying human hormonal aging. For this purpose, human sebaceous gland cells were maintained under a hormone-substituted environment. This environment consisted of growth factors and sex steroids in concentrations corresponding to those circulating in young and postmenopausal women. The authors suggest that hormone decline, occurring with age, may play a significant role not only in the maintenance of skin homeostasis but also in the initiation of aging. Furthermore, skin, the largest organ of the body, offers an alternative approach to understanding the molecular mechanisms underlining the aging process.

This chapter presents the development stages of a theoretical model of Knowledge Absorptive Capacity (KAC) that shows how most, if not all, firms in developing countries initiate, implement, assimilate, improve, and develop external knowledge. The chapter reviews the literature, models, and frameworks related to knowledge absorptive capacity. The chapter utilizes a qualitative content analysis as an explanation method in case study research to validate the proposed model. The chapter then analyzes Korean firms as a case in point to illustrate how Korean firms have built their knowledge absorptive capacity. The model consists of four stages: 1) knowledge initiation, 2) knowledge imitation, 3) knowledge improvement, and finally, 4) knowledge innovation or 4KI. The framework shows four development stages at Korean firms as: 1) entrance of foreign companies into the Korean market and their reluctance to transfer their knowledge and information sharing to Korean firms, initiating its knowledge absorptive capacity, 2) Korean firms started knowledge absorptive capacity by means of imitating knowledge from external (especially foreign firms), 3) it then developed knowledge absorptive capacity by means of improving external knowledge, and finally, 4) capability to create their own knowledge and becoming one of the leading economy in the world which challenges firms from advanced countries in the global market. The chapter also highlights the developmental changes in the electronics industry of Korea. Keeping past experiences in consideration, the authors conclude that this model provides useful implications for developing economies, known as latecomers following the same pattern of KAC.

This chapter presents the development stages of a theoretical model of Knowledge Absorptive Capacity (KAC) that shows how most, if not all, firms in developing countries initiate, implement, assimilate, improve, and develop external knowledge. The chapter reviews the literature, models, and frameworks related to knowledge absorptive capacity. The chapter utilizes a qualitative content analysis as an explanation method in case study research to validate the proposed model. The chapter then analyzes Korean firms as a case in point to illustrate how Korean firms have built their knowledge absorptive capacity. The model consists of four stages: 1) knowledge initiation, 2) knowledge imitation, 3) knowledge improvement, and finally, 4) knowledge innovation or 4KI. The framework shows four development stages at Korean firms as: 1) entrance of foreign companies into the Korean market and their reluctance to transfer their knowledge and information sharing to Korean firms, initiating its knowledge absorptive capacity, 2) Korean firms started knowledge absorptive capacity by means of imitating knowledge from external (especially foreign firms), 3) it then developed knowledge absorptive capacity by means of improving external knowledge, and finally, 4) capability to create their own knowledge and becoming one of the leading economy in the world which challenges firms from advanced countries in the global market. The chapter also highlights the developmental changes in the electronics industry of Korea. Keeping past experiences in consideration, the authors conclude that this model provides useful implications for developing economies, known as latecomers following the same pattern of KAC.

Surface roughness can reduce the performance of a system of fluid mechanics due to an increase in frictional resistance. The ship hull, which is overgrown by biofouling, experiences a drag penalty which causes energy wastage and increased emission levels. The phenomenon of fluid flow that passes over a rough surface still has many questions, one of which is the phenomenon of frictional resistance on heterogeneous roughness in the streamwise direction. In the ship hull, biofouling generally grows heterogeneous along the hull with many factors. RANSE-based Computational Fluid Dynamics was used to investigate the friction resistance for heterogeneous roughness phenomenon. The modified wall-function method represented equivalent sand grain roughness (ks) and a roughness function were applied together with k-epsilon turbulence model to simulate rough wall turbulent boundary layer flow. As the heterogeneous roughness, three different ks values were denoted as P (ks = 81.25 μm), Q (ks = 325.00 μm) and R (ks = 568.75 μm), and they are arranged by all possible combinations. The combined roughness, whether homogeneous (PPP, QQQ, or RRR) and inhomogeneous (PQR, PRQ, QPR, etc.), results in unique skin friction values. The step-change in the height of the heterogeneous roughness produced a sudden change in the local skin friction coefficient in the form of overshoot or undershoot, followed by a relaxation where the inhomogeneous local skin friction is slowly returning to the homogeneous local one, which was explained in more detail by plotting the distribution of the mean velocity profile near the step-up or step-down. The order of roughness arrangement in a streamwise heterogenous roughness pattern plays a key role in generating overall skin friction with values increasing in the following order: PQR < PRQ < QPR < QRP < RPQ < RQP. Those inhomogeneous cases with three different values of ks can be represented by a single value (being like homogeneous) by the calculations provided in this paper.

Ships navigating in ice-covered waters experience local and global ice loads due to ice-hull interaction. The design of a ship with good ice performance requires adequate assessment of these forces. Recently, an increased activity in developing numerical models of ice-hull interaction in level ice has been observed, owed to the increased computational capabilities. However, certain semi-empirical icebreaking patterns inevitably influencing the interaction process have been implemented in the majority of interaction models used for the assessment of ice performance of ships. Therefore, an attempt using a quasi-static numerical approach to model the initiation of icebreaking pattern in level ice has been made and is presented in this paper. The term initiation herein denotes the creation of circumferential cracks, disregarding thus the succeeding radial cracks. The concept used in the model features a set of radially oriented ice beams at the interaction zone. The model accounts for the bow geometry and the properties of the encountered ice. The icebreaking pattern for a case study ship is simulated using the developed model. Lastly, this paper discusses the sensitivity of the model with respect to the bow shape.