The interface between collagen and the mineral reinforcement phase, carbonated hydroxyapatite (cAp), is essential for bone’s remarkable functionality as a biological composite material. The very ...small dimensions of the cAp phase and the disparate natures of the reinforcement and matrix are essential to the material’s performance but also complicate study of this interface. This article summarizes what is known about the cAp-collagen interface in bone and begins with descriptions of the matrix and reinforcement roles in composites, of the phases bounding the interface, of growth of cAp growing within the collagen matrix, and of the effect of intra- and extrafibrilar mineral on determinations of interfacial properties. Different observed interfacial interactions with cAp (collagen, water, non-collagenous proteins) are reviewed; experimental results on interface interactions during loading are reported as are their influence on macroscopic mechanical properties; conclusions of numerical modeling of interfacial interactions are also presented. The data suggest interfacial interlocking (bending of collagen molecules around cAp nanoplatelets) and water-mediated bonding between collagen and cAp are essential to load transfer. The review concludes with descriptions of areas where new research is needed to improve understanding of how the interface functions.
This review highlights recent advances in X-ray microcomputed tomography (microCT) as applied to materials, specifically advances made since the first materials microCT review appeared in ...International Materials Reviews. Improvements in instrumentation are covered, and one focus is microCT using phase (as opposed to absorption) contrast. Instead of grouping studies by disciplines, the reviewed reports are organised by type of application, specifically the study of the spatial distribution of phases, of cellular solids (including static and temporally evolving structures, fibrous network solids, mineralised tissues and biomedical applications), of channel structures, of deformation, fatigue and fracture, of processing and of corrosion and environmental interactions. Metrology applications are covered briefly, and several applications where microCT is combined with position resolved X-ray scattering are described in more detail. The accuracy of microCT reconstructions is discussed before data handling challenges are outlined. The review closes with speculations on the future directions of materials microCT.
▶ Tests of different pearlitic and bainitic rail grades on a full scale rail wheel test rig. ▶ With increased pearlitic steel quality (increased Brinell hardness) the RCF and wear resistance is ...increased. ▶ Bainitic rail steels show a maximum of RCF resistance but wear resistance is reduced compared to pearlitic steels with the same Brinell hardness. ▶ Track test results show the same trends but due to some significant differences between track and rig conditions the absolute values differ.
This paper investigates the wear and RCF behaviour of several pearlitic and bainitic rail steels on a full scale test rig at voestalpine Schienen GmbH and also in several track tests. On the test rig a clear dependence between hardness of the pearlitic grades and the resistance against wear and RCF is seen. The same is found in track tests however the results especially in low wear regimes concerning higher hardness grades are not as distinct as on the test rig. Track behaviour also indicated the improved RCF resistance of higher hardness steels. Bainitic steels show a slightly different behaviour – the wear resistance is reduced compared to a pearlitic steel with the same hardness level though the RCF resistance is higher (both on the rig and in track if data available). Although the trends are consistent on the rig and in track, the absolute values concerning wear and RCF differ. Finally an outlook concerning modifications and upgrades for the test rig to shorten this gap is given.
Management of rolling contact fatigue (RCF) risk is a critical maintenance activity in railway operations. Practical means of RCF mitigation involve: 1) preventative and corrective grinding to remove ...RCF cracks; 2) management of wheel and rail profiles to minimize peak contact pressures; and 3) selection of appropriate rail metallurgy. In addition, reduction of traction forces by application of dry film Top of Rail friction modifiers (FM) has recently been shown to reduce crack growth and extend grinding intervals.
Hydro-pressurisation and crack face lubrication are processes by which liquid materials (e.g., water), enter pre-existing RCF cracks and under wheel/rail contact pressure and cause accelerated crack growth, leading to spalling and shelling on rail and wheels. Thus, any liquid material added deliberately to the wheel/rail interface should be considered carefully in terms of the potential for aggravating RCF damage. This study compares the impact on hydro-pressurization and crack face lubrication of different types of materials designed for application to the top of rail using twin disc testing. One type of FM material is water-based, drying providing solid particles to the rail-wheel contact. Two other types are oil or oil-plus-water-based (hybrid material) that do not naturally dry and have been introduced more recently to the market. In addition, a commonly used gauge face lubricant (grease) was evaluated.
•First assessment of wear/RCF behaviour with a range of Top of Rail Friction Modifiers.•First full analysis of crack characteristics.•Key differences in behaviour found between water & oil/grease based friction modifiers.
This commentary discusses loose versus tight control of biomineralization products and how this evolved flexibility. Concomitant improved functionality may be more widespread than commonly thought.
In an effort to develop a new therapy for prostate cancer (PCa) bone metastases, we have created Ad.dcn, a recombinant oncolytic adenovirus carrying the human decorin gene. Infection of PC-3 and ...DU-145, the human prostate tumor cells, with Ad.dcn or a non-replicating adenovirus Ad(E1-).dcn resulted in decorin expression; Ad.dcn produced high viral titers and cytotoxicity in human prostate tumor cells. Adenoviral-mediated decorin expression inhibited Met, the Wnt/β-catenin signaling axis, vascular endothelial growth factor A, reduced mitochondrial DNA levels and inhibited tumor cell migration. To examine the antitumor response of Ad.dcn, PC-3-luc cells were inoculated in the left heart ventricle to establish bone metastases in nude mice. Ad.dcn, in conjunction with control replicating and non-replicating vectors were injected via tail vein. The real-time monitoring of mice, once a week, by bioluminescence imaging and X-ray radiography showed that Ad.dcn produced significant inhibition of skeletal metastases. Analyses of the mice at the terminal time point indicated a significant reduction in the tumor burden, osteoclast number, serum tartrate-resistant acid phosphatase 5b levels, osteocalcin levels, hypercalcemia, inhibition of cancer cachexia and an increase in the animal survival. Based on these studies, we believe that Ad.dcn can be developed as a potential new therapy for PCa bone metastasis.
TROP2 is a powerful cancer driver in colorectal cancer cells. Divergent epigenetic regulation mechanisms for the corresponding TACSTD2 gene exist such as miRNAs or DNA methylation. However, the role ...of TACSTD2 promoter hypermethylation in colorectal cancer has not been investigated yet. In this study, TROP2 expression strongly correlated with promoter methylation in different colorectal tumor cell lines. Treatment with 5-Azacytidine, a DNMT1 inhibitor, led to demethylation of the TACSTD2 promoter accompanied by an increase in TROP2 protein expression. TROP2 expression correlated with promoter methylation in vivo in human colon tumor tissue, thereby verifying promoter methylation as an important factor in the regulation of TROP2 expression in colorectal cancer. When performing a ChIP-Seq analysis in HCT116 and HT29 cells, we found that TACSTD2 promoter demethylation was accompanied by tri-methylation of H3K4. In silico analysis of GSE156613 data set confirmed that a higher binding of histone mark H3K4me3 around the TACSTD2 promoter was found in TACSTD2 high expressing tumors of colon cancer patients compared to the corresponding adjacent tumor tissue. Moreover, the link between TROP2 and the H3K4me3 code was even evident in tumors showing high intratumoral heterogeneity for TROP2 staining. Our data provide novel evidence for promoter demethylation and simultaneous gains of the active histone mark H3K4me3 across CpG-rich sequences, both being complementary mechanisms in the transcriptional regulation of TACSTD2 in colon cancer. The functional consequences of TROP2 loss in colorectal cancer needs to be further investigated.
This paper investigates the damage behaviour of several pearlitic rail steels with special focus on three specific damage mechanisms – wear, plastic flow and rolling contact fatigue (RCF, head checks ...in particular). Multiple tests were conducted on a full scale test-rig at voestalpine Schienen GmbH under dry contact conditions. The obtained results were compared with data from selected track tests. The test-rig is capable of producing realistic contact conditions that allow the formation of wear and RCF defects in very short time periods within 100,000 wheel passes. The test-rig results showed the improved wear and RCF resistance of high strength steels clearly. Additionally, a system wear analysis was conducted to outline the interaction of these high strength rail steels with a standard wheel steel. Although the trends are consistent on the rig and in track, the absolute values concerning wear and RCF differ due to some specific differences between track and test-rig conditions. Finally ideas are postulated that explain on one hand the test-rig specific wear behaviour of the rail grades and on the other hand the formation of periodic, rail grade dependent crack spacing of the defect type head checks.
•Full scale laboratory tests of different pearlitic rail steels.•Comprehensive damage analysis with respect to wear, plastic deformation and periodic surface cracks (Head Checks).•Stating a possible explanation for grade dependent crack spacing by combining test rig data with severe plastic deformation data.•Comparing test-rig results with real track conditions highlighting the similarities, differences and restrictions of full scale laboratory testing.
Fatty acid-derived acyl chains of phospholipids and lipoproteins are central to bacterial membrane fluidity and lipoprotein function. Though it can incorporate exogenous unsaturated fatty acids ...(UFA), Staphylococcus aureus synthesizes branched chain fatty acids (BCFA), not UFA, to modulate or increase membrane fluidity. However, both endogenous BCFA and exogenous UFA can be attached to bacterial lipoproteins. Furthermore, S. aureus membrane lipid content varies based upon the amount of exogenous lipid in the environment. Thus far, the relevance of acyl chain diversity within the S. aureus cell envelope is limited to the observation that attachment of UFA to lipoproteins enhances cytokine secretion by cell lines in a TLR2-dependent manner. Here, we leveraged a BCFA auxotroph of S. aureus and determined that driving UFA incorporation disrupted infection dynamics and increased cytokine production in the liver during systemic infection of mice. In contrast, infection of TLR2-deficient mice restored inflammatory cytokines and bacterial burden to wildtype levels, linking the shift in acyl chain composition toward UFA to detrimental immune activation in vivo. In in vitro studies, bacterial lipoproteins isolated from UFA-supplemented cultures were resistant to lipase-mediated ester hydrolysis and exhibited heightened TLR2-dependent innate cell activation, whereas lipoproteins with BCFA esters were completely inactivated after lipase treatment. These results suggest that de novo synthesis of BCFA reduces lipoprotein-mediated TLR2 activation and improves lipase-mediated hydrolysis making it an important determinant of innate immunity. Overall, this study highlights the potential relevance of cell envelope acyl chain repertoire in infection dynamics of bacterial pathogens.
In high multiplicity nucleus-nucleus collisions baryon-antibaryon annihilation and regeneration occur during the final hadronic expansion phase, thus distorting the initial equilibrium multiplicity ...ratios. We quantify the modifications employing the hybrid UrQMD transport model and apply them to the grand canonical partition functions of the Statistical Hadronization Model(SHM). We analyze minimum bias and central Pb+Pb collision data at SPS and LHC energy. We explain the Pion to Proton ratio puzzle. We also reproduce the deuteron to proton ratio at LHC energy by the SHM, and by UrQMD after attaching a phase space coalescence process. We discuss the resulting (T,μB) diagram.
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