Mechanical model for a collagen fibril pair in extracellular matrix

In this paper, we model the mechanics of a collagen pair in the connective tissue extracellular matrix that exists in abundance throughout animals, including the human body. This connective tissue comprises repeated units of two main structures, namely collagens as well as axial, parallel and regular anionic glycosaminoglycan between collagens. The collagen fibril can be modeled by Hooke's law whereas anionic glycosaminoglycan behaves more like a rubber-band rod and as such can be better modeled by the worm-like chain model. While both computer simulations and continuum mechanics models have been investigated the behavior of this connective tissue typically, authors either assume a simple form of the molecular potential energy or entirely ignore the microscopic structure of the connective tissue. Here, we apply basic physical methodologies and simple applied mathematical modeling techniques to describe the collagen pair quantitatively. We find that the growth of fibrils is intimately related to the maximum length of the anionic glycosaminoglycan and the relative displacement of two adjacent fibrils, which in return is closely related to the effectiveness of anionic glycosaminoglycan in transmitting forces between fibrils. These reveal the importance of the anionic glycosaminoglycan in maintaining the structural shape of the connective tissue extracellular matrix and eventually the shape modulus of human tissues. We also find that some macroscopic properties, like the maximum molecular energy and the breaking fraction of the collagen, are also related to the microscopic characteristics of the anionic glycosaminoglycan

Role of Calcitonin Gene-Related Peptide in Bone Repair after Cyclic Fatigue Loading

Calcitonin gene related peptide (CGRP) is a neuropeptide that is abundant in the sensory neurons which innervate bone. The effects of CGRP on isolated bone cells have been widely studied, and CGRP is currently considered to be an osteoanabolic peptide that has effects on both osteoclasts and osteoblasts. However, relatively little is known about the physiological role of CGRP in-vivo in the skeletal responses to bone loading, particularly fatigue loading.We used the rat ulna end-loading model to induce fatigue damage in the ulna unilaterally during cyclic loading. We postulated that CGRP would influence skeletal responses to cyclic fatigue loading. Rats were fatigue loaded and groups of rats were infused systemically with 0.9% saline, CGRP, or the receptor antagonist, CGRP(8-37), for a 10 day study period. Ten days after fatigue loading, bone and serum CGRP concentrations, serum tartrate-resistant acid phosphatase 5b (TRAP5b) concentrations, and fatigue-induced skeletal responses were quantified. We found that cyclic fatigue loading led to increased CGRP concentrations in both loaded and contralateral ulnae. Administration of CGRP(8-37) was associated with increased targeted remodeling in the fatigue-loaded ulna. Administration of CGRP or CGRP(8-37) both increased reparative bone formation over the study period. Plasma concentration of TRAP5b was not significantly influenced by either CGRP or CGRP(8-37) administration.CGRP signaling modulates targeted remodeling of microdamage and reparative new bone formation after bone fatigue, and may be part of a neuronal signaling pathway which has regulatory effects on load-induced repair responses within the skeleton

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Multiscale modeling of human bone

The article of record as published may be found at http://dx.doi.org/10.1007/s41939-018-0013-0A multiscale modeling technique was developed to predict mechanical properties of human bone, which utilizes the hierarchies of human bone in different length scales from nanoscale to macroscale. Bone has a unique structure displaying high stiffness with minimal weight. This is achieved through a hierarchy of complex geometries composed of three major materials: hydroxyapatite, collagen and water. The identifiable hierarchical structures of bone are hydroxyapatite, tropocollagen, fibril, fiber, lamellar layer, trabecular bone, cancellous bone and cortical bone. A helical spring model was used to represent the stiffness of collagen. A unit cell-based micromechanics model computed both the normal and shear stiffness of fibrils, fibers, and lamellar layers. A laminated composite model was applied to cortical and trabecular bone, while a simplified finite element model for the tetrakaidecahedral shape was used to evaluate cancellous bone. Modeling bone from nanoscale components to macroscale structures allows the influence of each structure to be assessed. It was found that the distribution of hydroxyapatite within the tropocollagen matrix at the fibril level influences the macroscale properties significantly. Additionally, the multiscale analysis model can vary any parameter of any hierarchical level to determine its effect on the bone property. With so little known about the detailed structure of nanoscale and microscale bone, a model encompassing the complete hierarchy of bone can be used to help validate assumptions or hypotheses about those structures

India's indigenization of military aircraft design and manufacturing: Towards a fifth-generation fighter

India’s desire to transform itself into an international military power has brought about a rapid shift in its approach to procuring military hardware. The indigenization of India’s military manufacturing capacity forms an integral part of the strategic objectives of Indian military services, with its realization being a function of significant government investment in strategic technologies. This has a number of ramifications. An indigenous Indian military capacity, particularly in the field of aviation, forms a key part of India’s ambition of achieving regional air superiority, or even supremacy, and being capable of power projection. This is particularly in response to China’s increasing presence in South Asian airspace. A burgeoning Indian military manufacturing machine based on a comparative advantage in skilled technicians and lower-cost labour, together with strategic collaboration with foreign military hardware manufacturers, may also lead to neighbouring countries looking to India as a source of competitively priced military hardware. In short, this chapter seeks to analyse the rationale behind India’s attempt to become militarily self-sufficient in the field of aviation, discuss the technical, economic and political context in which it is achieving this transformation, and assess the potential outlook of success for India’s drive to achieve self-sufficiency in the arena of military aviation. This chapter will do so by using the case of India’s attempt to develop a fifth-generation fighter aircraft