Key Structural Components Research Articles

Molecular Dynamic Simulation Approach Provides Insights into the Tumorigenesis of the N Terminal Portion of the Retinoblastoma Protein

The Retinoblastoma (Rb) protein is a master regulator of fundamental biological processes, such as the cell cycle entry, DNA replication, and apoptosis. Its functional inactivation is strongly implicated in the development of cancer, including retinoblastoma, osteosarcoma, breast, and lung cancer. Here we analyzed structural organization of the N terminal portion of Rb (RbN), known to harbor familial tumorigenic in‐frame deletions of exons 4, 5, 7 and 9, and exert a direct inhibitory effect on CMG helicase and DNA polymerase α via a bipartite mechanism. By utilizing the Molecular Dynamic Simulations, we reconstructed these RbN variants to visualize how accessibility of the CMG helicase and DNA polymerase α inhibitory domains is altered in the Δ4, Δ5, Δ7, and Δ9 RbN mutants. Our RbN models further supported the proposed bipartite mechanism of DNA replication inhibition by RbN and highlighted key structural components of RbN’s inhibitory domains. Our results reinforced previous studies, and provided insights on how mutations within the RbN contribute to tumorigenesis.

Sycp2 is essential for synaptonemal complex assembly, early meiotic recombination and homologous pairing in zebrafish spermatocytes.

Meiotic recombination is essential for faithful segregation of homologous chromosomes during gametogenesis. The progression of recombination is associated with dynamic changes in meiotic chromatin structures. However, whether Sycp2, a key structural component of meiotic chromatin, is required for the initiation of meiotic recombination is still unclear in vertebrates. Here, we describe that Sycp2 is required for assembly of the synaptonemal complex and early meiotic events in zebrafish spermatocytes. Our genetic screening by N-ethyl-N-nitrosourea mutagenesis revealed that ietsugu (its), a mutant zebrafish line with an aberrant splice site in the sycp2 gene, showed a defect during meiotic prophase I. The its mutation appeared to be a hypomorphic mutation compared to sycp2 knockout mutations generated by TALEN mutagenesis. Taking advantage of these sycp2 hypomorphic and knockout mutant lines, we demonstrated that Sycp2 is required for the assembly of the synaptonemal complex that is initiated in the vicinity of telomeres in wild-type zebrafish spermatocytes. Accordingly, homologous pairing, the foci of the meiotic recombinases Dmc1/Rad51 and RPA, and γH2AX signals were largely diminished in sycp2 knockout spermatocytes. Taken together, our data indicate that Sycp2 plays a critical role in not only the assembly of the synaptonemal complex, but also early meiotic recombination and homologous pairing, in vertebrates.

Differential effect of biophenols on attenuation of AGE-induced hemoglobin aggregation

Despite most studied activities of natural biophenols rely on antioxidant properties, little clues explored their key structural components with regard to opposing action on glycation-induced aggregation. Herein, human hemoglobin (hHb)/fructose system used to decipher if structural peculiarities of two biophenols “chlorogenic acid (CGA) and curcumin (CUR)” are effective toward AGEs-bridged aggregate formation. Suppression in amyloid cross-β formation was monitored by CD spectroscopy, fluorescence microscopy, ANS and AGE fluorescence. Reduction in molten globule structure of modified-Hb by CGA was corroborated with helix structure, thiol group and lysine residues content estimation for native, glycated and biophenols treated samples. ThT and Congo red assays showed the cross-β breaking properties of CGA. Molecular docking outcomes revealed the positioning of CGA/CUR is driven by “aromatic interactions” with Trp β1180 and Tyr α2540. These interactions are modulated by the structural constraints such as number of hydroxyl groups and their methylation status directing the biophenols to the amyloidogenic core. The results are applicable to formulation of small-molecule nutraceuticals for treatment of conformational diseases.

Chromosome Segregation: Evolving a Plastic Chromosome-Microtubule Interface.

Despite a conserved requirement in mediating chromosome segregation, kinetochores display remarkable plasticity in their structure and composition. New work in holocentric insect species highlights the molecular rewiring that occurs when key structural components of the kinetochore are lost and centromere structure is changed.

Structures of immature EIAV Gag lattices reveal a conserved role for IP6 in lentivirus assembly.

Retrovirus assembly is driven by the multidomain structural protein Gag. Interactions between the capsid domains (CA) of Gag result in Gag multimerization, leading to an immature virus particle that is formed by a protein lattice based on dimeric, trimeric, and hexameric protein contacts. Among retroviruses the inter- and intra-hexamer contacts differ, especially in the N-terminal sub-domain of CA (CANTD). For HIV-1 the cellular molecule inositol hexakisphosphate (IP6) interacts with and stabilizes the immature hexamer, and is required for production of infectious virus particles. We have used in vitro assembly, cryo-electron tomography and subtomogram averaging, atomistic molecular dynamics simulations and mutational analyses to study the HIV-related lentivirus equine infectious anemia virus (EIAV). In particular, we sought to understand the structural conservation of the immature lentivirus lattice and the role of IP6 in EIAV assembly. Similar to HIV-1, IP6 strongly promoted in vitro assembly of EIAV Gag proteins into virus-like particles (VLPs), which took three morphologically highly distinct forms: narrow tubes, wide tubes, and spheres. Structural characterization of these VLPs to sub-4Å resolution unexpectedly showed that all three morphologies are based on an immature lattice with preserved key structural components, highlighting the structural versatility of CA to form immature assemblies. A direct comparison between EIAV and HIV revealed that both lentiviruses maintain similar immature interfaces, which are established by both conserved and non-conserved residues. In both EIAV and HIV-1, IP6 regulates immature assembly via conserved lysine residues within the CACTD and SP. Lastly, we demonstrate that IP6 stimulates in vitro assembly of immature particles of several other retroviruses in the lentivirus genus, suggesting a conserved role for IP6 in lentiviral assembly.

Інноваційно-активний університет: підґрунтя виникнення та особливості функціонування

The article aims at defining the essence of the "innovatively active university" concept as well as the key characteristics and structural components of such a university; substantiating the management framework of educational innovations taking place at a university and providing a flexible combination of teaching, research and entrepreneurship. The article considers the regulatory support present in Ukraine as for the functioning of the education system, including all its levels and subsystems, the activities of various educational institutions, public or private, irrespective of their attendance modes. The analysis of definitions of the "innovative university" term suggested by various scientists has been carried out thus allowing the author to consider this concept within the functional approach. It has been determined that the given terms are similar in their meaning, but still the difference between them is rather significant. For a deeper understanding of the concept, decomposition of the abovementioned definitions into the main components has been made according to the following points: the essential component of the concept; activity areas of the innovative university; the mission of an innovative university. The "innovatively active university" has been defined as an entrepreneurial organization that possesses the resource readiness to promote accelerated social and economic development through intensive transfer of knowledge and technology generated at the university due to partnership relations established with stakeholders (labor market actors, government and NGOs). Models of the innovative university and their distinctive features have been suggested. The main characteristics of the innovative university that contribute to the development of new systems and management processes have been outlined. The ways of managing innovative universities have been considered and the management framework of educational innovations at a university has been offered. Prospects for further research in this area lie in the following: analyzing the competitive strength of universities around the world to determine the internal and external features of an innovatively active university, helping it to achieve and maintain a high level of competitiveness and attractiveness.

Immunomodulatory Activities of the Heparan Sulfate Mimetic PG545.

Heparanase regulates multiple biological activities that enhance tumor growth and metastatic spread. Heparanase cleaves and degrades heparan sulfate (HS), a key structural component of the extracellular matrix that serves as a barrier to cell invasion and also as a reservoir for cytokines and growth factors critical for tumor growth and metastasis. For this reason, heparanase is an attractive target for the development of novel anti-cancer therapies. Pixatimod (PG545), a heparanase inhibitor, has shown promising results in the treatment of multiple tumor types. PG545 offers a diversity of mechanisms of action in tumor therapy that include angiogenic inhibition, inhibition of growth factor release, inhibition of tumor cell migration, tumorcell apoptosis, activation of ER stress response, dysregulation of autophagy, and NK cell activation. Further investigation into the role that heparanase and its inhibitors play in tumor therapy can lead to the development of effective tumor therapies.

Numerical analysis on the deformation behavior of cylindrical tubes with end-capped shells under axial impact

Thin-walled tubes are designed as the key structural components of the majority of modern transportation vehicles owing to their excellent energy absorbing capability. Extensive research has been carried out on various types of materials and structures with good energy absorbing capability to mitigate the peak crushing force during impact event. In the current research article, numerical analysis on the axial buckling behavior and crashworthiness performance of cylindrical tubes with end-capped shells were executed. The objective of using end-capped shells is to decrease the initial peak crushing force and subsequently to enhance the energy absorption capability of the tube. The axial impact crushing behavior of the proposed cylindrical tubes with capped shells showed less initial peak crushing force than the traditional tubes. Overall outcomes from the present study indicated that, the weight reduction is still the most cost-effective means to reduce fuel consumption and greenhouse gases from the transportation sector.

Occludin regulation of blood-brain barrier and potential therapeutic target in ischemic stroke.

Occludin is a key structural component of the blood–brain barrier (BBB) that has recently become an important focus of research in BBB damages. Many studies have demonstrated that occludin could regulate the integrity and permeability of the BBB. The function of BBB depends on the level of occludin protein expression in brain endothelial cells. Moreover, occludin may serve as a potential biomarker for hemorrhage transformation after acute ischemic stroke. In this review, we summarize the role of occludin in BBB integrity and the regulatory mechanisms of occludin in the permeability of BBB after ischemic stroke. Multiple factors have been found to regulate occludin protein functions in maintaining BBB permeability, such as Matrix metalloproteinas-mediated cleavage, phosphorylation, ubiquitination, and related inflammatory factors. In addition, various signaling pathways participate in regulating the occludin expression, including nuclear factor-kappa B, mitogen-activated protein kinase, protein kinase c, RhoK, and ERK1/2. Emerging therapeutic interventions for ischemic stroke targeting occludin are described, including normobaric hyperoxia, Chinese medicine, chemical drugs, genes, steroid hormones, small molecular peptides, and other therapies. Since occludin has been shown to play a critical role in regulating BBB integrity, further preclinical studies will help evaluate and validate occludin as a viable therapeutic target for ischemic stroke.

PRACTICE-ORIENTED EDUCATIONAL PROGRAM OF ACTIVITIES OF THE CHILDREN ENVIRONMENTAL ASSOCIATION AS A TOOL TO FORM THE SEVENTH AND EIGHTH-GRADERS’ ENVIRONMENTAL RESPONSIBILITY

The Article covers the problem of forming form the seventh and eighth-graders’ environmental responsibility in additional (informal education), which is caused by focus of the modern education on forming the environment-orientated moral personality qualities, which can assure the switching of the society over to the sustainable development; by significant possibilities of the children environmental associations in developing the environmental responsibility, and the lack of scientifically substantiated, approbated practice-oriented programs favoring the solution to this problem. The article is aimed at substantiating the specificity of a goal, content-related, procedural and technological components of the program of activities of the children environmental association “My environmental responsibility: to the co-creation with the nature”; opening of the pedagogical раскрытие педагогического tools of diagnostics of its efficiency, presentation of results of the program implementation in the educational practice. As the leading theoretical methods, simulation and designing were used, which make it possible to develop the key structural components of the program. The basic empirical method of the research is a pedagogical experiment, during which the program efficiency was diagnosed in terms of criteria and indicators of maturity of the environmental responsibility components with 210 members of the children environmental associations at the age from 11 to 14 years old. The article considers the theoretical and methodological basis of the program, which includes the ideas of ecohumanism, coevolution and sustainable development; an axiological, personal-activity and ecopsychological approaches, which provide for an organization of the developing ecology-оriented educational environment of the children association as a tool of forming the environmental responsibility. The article presents the program content, which consists of two components (external and internal components), discusses the succession of forming the environmental responsibility, which includes four stages and substantiates a technology of forming the environmental responsibility in the children association, which is presented by a system of environmentally responsible businesses. The article materials are of practical value to school teachers, additional education teachers, students of pedagogical specialties and advisers of children environmental associations.

Creating Common Ground

Growing from an invited workshop on interdisciplinary learning the authors led at their institution’s annual faculty retreat, this manuscript offers a framework for encouraging faculty from diverse disciplines to consider and evaluate their teaching, scholarship, and service in interdisciplinary ways. In this paper, we present an application of a process that integrates Repko’s (2008) suggested criteria for interdisciplinarians, Doran, Miller, and Cunningham’s (1981) conceptualization of S.M.A.R.T. goals, and McCoy and Gardner’s (2012) five key social structural components, in order to further cultivate faculty members' identities as interdisciplinarians. We conclude by summarizing participants’ comments in order to offer concrete examples of how the workshop yielded specific action plans for faculty members’ own interdisciplinarity within their teaching, research, and service activities. Taken together, this process challenges the traditional “silos” of academic work to help faculty reach across disciplinary boundaries. As such, this framework provides a roadmap for faculty and institutions interested in purposefully and meaningfully facilitating interdisciplinarity across a variety of academic settings.

Monotonic shear strength of headed studs in reinforced infill walls

Headed studs are key components of structures which facilitate composite behavior between steel and concrete elements. In steel building structures, reinforced concrete infill walls surrounded by a stiff steel frame is a common example of a composite structure used to resist horizontal loads such as those produced by earthquakes or wind. To this end, these types of concrete walls need to be anchored to the steel frame with headed studs which must withstand shear and tensile forces (AISC 360). To properly design headed stud anchors in concrete walls, it is first necessary to understand their behavior when subjected to monotonic shear forces considering edge conditions and reinforcing details that may influence the stud strength.Few tests have examined headed studs subjected to monotonic shear with typical boundary effects in reinforced infill walls, so a new experimental study on 17 specimens explores the behavior of headed studs exposed to monotonic shear loading with group effects. The experiments showed that the strength of studs installed in infill walls with edge conditions is well predicted (average error in prediction is smaller than 10%) by ACI 318, AISC 360 and EC-4. However, when group effects of anchors are included in the analysis of infill walls, only the ACI 318 is able to predict the behavior.

Identification of Pparγ-modulated miRNA hubs that target the fibrotic tumor microenvironment

Liver fibrosis interferes with normal liver function and facilitates hepatocellular carcinoma (HCC) development, representing a major threat to human health. Here, we present a comprehensive perspective of microRNA (miRNA) function on targeting the fibrotic microenvironment. Starting from a murine HCC model, we identify a miRNA network composed of 8 miRNA hubs and 54 target genes. We show that let-7, miR-30, miR-29c, miR-335, and miR-338 (collectively termed antifibrotic microRNAs [AF-miRNAs]) down-regulate key structural, signaling, and remodeling components of the extracellular matrix. During fibrogenic transition, these miRNAs are transcriptionally regulated by the transcription factor Pparγ and thus we identify a role of Pparγ as regulator of a functionally related class of AF-miRNAs. The miRNA network is active in human HCC, breast, and lung carcinomas, as well as in 2 independent mouse liver fibrosis models. Therefore, we identify a miRNA:mRNA network that contributes to formation of fibrosis in tumorous and nontumorous organs of mice and humans.

Transformation Of Law And Legal Consciousness In Transitive Societies In Globalized World

Introduction. The legal systems of different countries in a globalized world are unified by norms of international law. In this context the question arises: are countries integrating into the globalized community capable of ensuring the practical implementation of international legal obligations into their legal systems? It determines the aim and the tasks which are to define the key structural components causing the transformation of law and legal consciousness in transitive societies in a globalized world. Research methods are structural-functional, socio-cultural and comparative approaches in their dialectical unity. Research results: in our study we assume that the functions of law determine the existing type of society, which in turn influences the whole set of legal relations and is reflected in the manifestations of law and legal consciousness. Taken into account that in transitive societies, the transition to a liberal system of relations has not occurred, the functions of the legal mechanism become dysfunctional in nature, and the laws do not meet the criteria of justice. In such circumstances, dissimulation of law is rooting in the social space while support and production of fiction becomes the only one single possible sociality. Discussion. In transitive societies, a paternalistic mechanism of "securing" rights as privileges (Berman) is dominant. As a result, the rights are nullified, not reproduced at the level of being and, ultimately, do not reach the average citizen. On the grounds of impossibility of securing the law in the real life, the political and legal discourse of transitive societies affirms a manipulative component aimed at implanting the simulacra of the legal space. The very manipulation is used by the authorities as a mechanism for asserting non-law in the society. Conclusion. Despite the unification of the legal systems of different countries in accordance with the requirements of international law, people in most transitive societies of the traditionalist type continue to be trapped in the tribalism of interpersonal relationships. In such circumstances, the implementation of any legal ideas in the legislative system of the transitive countries becomes in practice prohibitive and repressive.

Creep of stainless steel under heat flux cyclic loading (500-1000C) with different mechanical preloads in a vacuum environment using 3D-DIC

In nuclear fusion reactors, the key structural component (i.e., the plasma-facing component) undergoes high heat flux cyclic loading. To ensure the safety of fusion reactors, an experimental study on the temperature-induced creep of stainless steel under heat flux cyclic loading was performed in the present work. The strains were measured using a stereo digital image correlation technique (3D-DIC). The influence of the heat haze was eliminated, owing to the use of a vacuum environment. The specimen underwent heat flux cycles (500 C-1000 C) with different mechanical preloads (0 kN, 10 kN, 30 kN, and 50 kN). The results revealed that, for a relatively large preload (for example, 50 kN), a single temperature cycle can induce a residual strain of up to 15000.

Market structure and economic sanctions: the 2010 rare earth elements episode as a pathway case of market adjustment

Studies identify cost as a key factor determining the effectiveness of economic sanctions. We argue that failing to account for market dynamics in the sector in which sanctions are imposed undermines the validity of estimates of the economic costs imposed on target countries, and we propose that market structure powerfully conditions sanctions effectiveness. To examine the effect of market structure, we trace the causal path through which economic sanctions purportedly lead to targets’ behavior changes, and we reveal the prevalence of adjustments that minimize the cost to the target. Our empirical data is drawn from a sanctions episode that can be evaluated as a best-case scenario for the imposition of effective economic sanctions: China’s 2010 embargo of rare earth elements supply to Japan. We show that Japan was able to adjust to avoid the Chinese sanction’s bite despite the dominance of Chinese producers and Japan’s seeming vulnerability as a key downstream consumer of rare earths. Our results show that measures of economic cost that fail to capture key components of market structure are not valid in assessing sanctions effectiveness, and the ability to impose economic costs on target countries is limited.

Prediction of Thermal Residual Stress and Microstructure in Direct Laser Metal Deposition via a Coupled Finite Element and Multiphase Field Framework

Direct laser metal deposition (DLMD) is a modern powder-fed additive manufacturing process, which builds up complex objects layer by layer, providing a potential capacity to produce key structural components specifically for the aerospace industry. The printing process is of a multidisciplinary nature, and has gained increasing attention in the areas of engineering mechanics, material science, control engineering and many other related fields. The quality control of the printed part depends on a large number of process parameters. The aim of this work, therefore, is to develop a coupled finite element and multiphase field framework, that provides an effective way to understand the quantitative relationship between the process parameters, temperature history, thermally-induced residual stresses and microstructures in the DLMD process. More specifically, the established multiscale framework is able to sequentially couple the heat transfer, metal melting/solidification, and stress analysis to simulate the macroscopic temperature distribution, thermal residual stresses and dendrite growth and solute segregation in a thin wall structure made of a binary nickel-copper alloy. The latest simulation technologies are used to model the process of progressive material deposition as well as the movement of the laser beam. It has been found that the high intensity laser introduced in DLMD can produce a complex thermal history and a significant level of thermal residual stresses and distortion. Microstructure predictions demonstrate the location-dependent morphology evolution, e.g., the dendrite spacing and the degree of solute segregation, attributed to the spatially variant temperature history.

ПРОЯВЛЕНИЯ СОЦИАЛЬНОЙ ОДАРЕННОСТИ ОБУЧАЮЩИХСЯ МЛАДШЕГО ПОДРОСТКОВОГО ВОЗРАСТА

Statement of the problem. The article presents the results of the research into manifestations of social giftedness among junior adolescents: communicative and organizational abilities, motivational orientations in interpersonal communication, emotional intelligence, as well as the correlation among the studied manifestations in the structure of social giftedness. The research contributes to the solution of the relevant educational problem of monitoring, development and psychological and pedagogical support of gifted students. The purpose of the article is to identify the manifestations of social giftedness among junior adolescents and to outline the directions of psychological and pedagogical work on the development of students’ social giftedness. The research methodology was the analysis and generalization of scientific works and publications of native and foreign psychologists on the problems of giftedness and social giftedness in the area of definitions, sources and components of the structure of giftedness, as well as the use of standardized survey methods in the framework of the psychometric approach to the study of key structural components of social giftedness (communicative and organizational abilities, prosocial motivation and social intelligence) and statistical methods (rank correlation, cluster analysis) to study the correlation of indicators in the structure of social giftedness among junior adolescents. Research results. The article presents the results of empirical research into manifestations of social giftedness among junior adolescents (communicative and organizational abilities, motivational orientations in interpersonal communication, indicators of emotional intelligence), demonstrating that only a small part of the studied sample of adolescents possesses abilities manifested at a high level in the structure of social giftedness. The article offers the results of statistical research showing the direct correlation among the components of the structure of social giftedness. In light of the model of social giftedness created on the basis of cluster analysis, the directions of psychological and pedagogical work on development and support of students’ social giftedness are offered. Conclusions. The research results and conclusions can be used by a psychologist of education while solving tasks in the framework of the function of psychological and pedagogical support of educational process in educational institutions and tasks of the Federal State Educational Standard of basic General education concerning the formation and development of students’ personal and interdisciplinary competencies. On the basis of the obtained data, a program of monitoring and development of students’ social giftedness with elements of training sessions and psychological games can be developed.

Adipose Tissue Quality in Aging: How Structural and Functional Aspects of Adipose Tissue Impact Skeletal Muscle Quality.

The interplay between adipose tissue and skeletal muscle and the impact on mobility and aging remain enigmatic. The progressive decline in mobility promoted by aging has been previously attributed to the loss of skeletal mass and function and more recently linked to changes in body fat composition and quantity. Regardless of body size, visceral and intermuscular adipose depots increase with aging and are associated with adverse health outcomes. However, the quality of adipose tissue, in particular abdominal subcutaneous as it is the largest depot, likely plays a significant role in aging outcomes, such as mobility decline, though its communication with other tissues such as skeletal muscle. In this review, we discuss the age-associated development of a pro-inflammatory profile, cellular senescence, and metabolic inflexibility in abdominal subcutaneous adipose tissue. Collectively, these facets of adipose tissue quality influence its secretory profile and crosstalk with skeletal muscle and likely contribute to the development of muscle atrophy and disability. Therefore, the identification of the key structural and functional components of adipose tissue quality—including necrosis, senescence, inflammation, self-renewal, metabolic flexibility—and adipose tissue-secreted proteins that influence mobility via direct effects on skeletal muscle are necessary to prevent morbidity/mortality in the aging population.

In SilicoTissue Engineering: A Coupled Agent-Based Finite Element Approach

Over the past two decades, the increase in prevalence of cardiovascular diseases and the limited availability of autologous blood vessels and saphenous vein grafts have motivated the development of tissue-engineered vascular grafts (TEVGs). However, compliance mismatch and poor mechanical properties of the TEVGs remain as two major issues that need to be addressed. Researchers have investigated the role of various culture conditions and mechanical conditioning in deposition and orientation of collagen fibers, which are the key structural components in the vascular wall; however, the intrinsic complexity of mechanobiological interactions demands implementing new engineering approaches that allow researchers to investigate various scenarios more efficiently. In this study, we utilized a coupled agent-based finite element analysis (AB-FEA) modeling approach to study the effect of various loading modes (uniaxial, biaxial, and equibiaxial), boundary conditions, stretch magnitudes, and growth factor concentrations on growth and remodeling of smooth muscle cell-populated TEVGs, with specific focus on collagen deposition and orientation. Our simulations (12 weeks of culture) showed that biaxial cyclic loading (and not uniaxial or equibiaxial) leads to alignment of collagen fibers in the physiological directions. Moreover, axial boundary conditions of the TEVG act as determinants of fiber orientations. Decreasing the serum concentration, from 10% to 5% or 1%, significantly decreased the growth and remodeling speed, but only affected the fiber orientation in the 1% serum case. In conclusion, in silico tissue engineering has the potential to evolve the future of tissue engineering, as it will allow researchers to conceptualize various interactions and investigate numerous scenarios with great speed. In this study, we were able to predict the orientation of collagen fibers in TEVGs using a coupled AB-FEA model in less than 8 h. Impact Statement Tissue-engineered vascular grafts (TEVGs) hold potential to replace the current gold standard of vascular grafting, saphenous vein grafts. However, developing TEVGs that mimic the mechanical performance of the native tissue remains a challenging task. We developed a computational model of the grafts' remodeling processes and studied the effects of various loading mechanisms and culture conditions on collagen fiber orientation, which is a key factor in mechanical performance of the grafts. We were able to predict the fiber orientations accurately and show that biaxial loading and axial boundary conditions are important factors in collagen fiber organization.