Method for Evaluating Cortical Bone Young's Modulus: Numerical Twin Reconstruction, Finite Element Calculation, and Microstructure Analysis.

The determination of bone mechanical properties remains crucial, especially to feed up numerical models. An original methodology of inverse analysis has been developed to determine the longitudinal elastic modulus of femoral cortical bone. The method is based on a numerical twin of a specific three-point bending test. It has been designed to be reproducible on each test result. In addition, the biofidelity of the geometric acquisition method has been quantified. As the assessment is performed at the scale of a bone shaft segment, the Young's modulus values obtained (between 9518.29 MPa and 14181.15 MPa) are considered average values for the whole tissue, highlighting some intersubject variability. The material microstructure has also been studied through histological analysis, and bone-to-bone comparisons highlighted discrepancies in quadrants microstructures. Furthermore, significant intrasubject variability exists since differences between the bone's medial-lateral and anterior-posterior quadrants have been observed. Thus, the study of microstructures can largely explain the differences between the elastic modulus values obtained. However, a more in-depth study of bone mineral density would also be necessary and would provide some additional information. This study is currently being setup, alongside an investigation of the local variations of the elastic modulus.

Mechanism and dynamics of fatty acid photodecarboxylase.

Fatty acid photodecarboxylase (FAP) is a photoenzyme with potential green chemistry applications. By combining static, time-resolved, and cryotrapping spectroscopy and crystallography as well as computation, we characterized Chlorella variabilis FAP reaction intermediates on time scales from subpicoseconds to milliseconds. High-resolution crystal structures from synchrotron and free electron laser x-ray sources highlighted an unusual bent shape of the oxidized flavin chromophore. We demonstrate that decarboxylation occurs directly upon reduction of the excited flavin by the fatty acid substrate. Along with flavin reoxidation by the alkyl radical intermediate, a major fraction of the cleaved carbon dioxide unexpectedly transformed in 100 nanoseconds, most likely into bicarbonate. This reaction is orders of magnitude faster than in solution. Two strictly conserved residues, R451 and C432, are essential for substrate stabilization and functional charge transfer.

Mechanical effects of load speed on the human colon.

The aim of this study was to examine the mechanical behavior of the colon using tensile tests under different loading speeds. Specimens were taken from different locations of the colonic frame from refrigerated cadavers. The specimens were submitted to uniaxial tensile tests after preconditioning using a dynamic load (1 m/s), intermediate load (10 cm/s), and quasi-static load (1 cm/s). A total of 336 specimens taken from 28 colons were tested. The stress-strain analysis for longitudinal specimens indicated a Young's modulus of 3.17 ±â€¯2.05 MPa under dynamic loading (1 m/s), 1.74 ±â€¯1.15 MPa under intermediate loading (10 cm/s), and 1.76 ±â€¯1.21 MPa under quasi-static loading (1 cm/s) with p < 0.001. For the circumferential specimen, the stress-strain curves indicated a Young's modulus of 3.15 ±â€¯1.73 MPa under dynamic loading (1 m/s), 2.14 ±â€¯1.3 MPa under intermediate loading (10 cm/s), and 0.63 ±â€¯1.25 MPa under quasi-static loading (1 cm/s) with p < 0.001. The curves reveal two types of behaviors of the colon: fast break behavior at high speed traction (1 m/s) and a lower break behavior for lower speeds (10 cm/s and 1 cm/s). The circumferential orientation required greater levels of stress and strain to obtain lesions than the longitudinal orientation. The presence of taeniae coli changed the mechanical response during low-speed loading. Colonic mechanical behavior varies with loading speeds with two different types of mechanical behavior: more fragile behavior under dynamic load and more elastic behavior for quasi-static load.

Influence of gender, age, shelf-life, and conservation method on the biomechanical behavior of colon tissue under dynamic solicitation.

BACKGROUND: Data from biomechanical tissue sample studies of the human digestive tract are highly variable. The aim of this study was to investigate 4 factors which could modify the mechanical response of human colonic specimens placed under dynamic solicitation until tissue rupture: gender, age, shelf-life and conservation method. METHODS: We performed uniaxial dynamic tests of human colonic specimens. Specimens were taken according to three different protocols: refrigerated cadavers without embalming, embalmed cadavers and fresh colonic tissue. A total of 143 specimens were subjected to tensile tests, at a speed of 1 m s-1. FINDINGS: Young's modulus of the different conservation protocols are as follows: embalmed, 3.08 ±â€¯1.99; fresh, 2.97 ±â€¯2.59; and refrigerated 3.17 ±â€¯2.05. The type of conservation does not modify the stiffness of the tissue (p = 0.26) but does modify the stress necessary for rupture (p < 0.001) and the strain required to obtain lesions of the outer layer and the inner layer (p < 0.001 and p < 0.05, respectively). Gender is also a factor responsible for a change in the mechanical response of the colon. The age of the subjects and the shelf-life of the bodies did not represent factors influencing the mechanical behavior of the colon (p > 0.05). INTERPRETATION: The mechanical response of the colon tissue showed a biphasic injury process depending on gender and method of preservation. The age and shelf-life of anatomical subjects do not alter the mechanical response of the colon.

Comparison of Two Intervertebral Disc Failure Models in a Numerical C4-C5 Trauma Model.

The intervertebral disc (IVD) is essential for the mobility and stability of the spine. During flexion-distraction injuries, which are frequent at the cervical spine level, the IVD is often disrupted. Finite element studies have been done to investigate injury mechanisms and patterns at the cervical spine. However, they rarely include IVD failure model. The aim of this paper was to implement and compare two types of IVD failure models and their impact on hyperflexion and hyperflexion-compression injuries simulations. The failure models were tested on a detailed C4-C5 finite elements model. The first failure model consisted in a maximal strain model applied to the elements of the annulus and nucleus. The second failure model consisted in the implementation of a rupture plane in the middle of the IVD with a tied interface created between the two sections. This interface is defined by threshold stress values of detachment in traction and shearing. The two failure models were tested in flexion only and in flexion-compression. The model without inclusion of an IVD failure model was also tested. Loads at failure and injury patterns were reported. Both failure models produce failure loads that were consistent with experimental data. Injury patterns observed were in agreement with experimental and numerical studies. However, in flexion-compression, the rupture plane model simulation reached important energy error due to high deformations in the IVD elements. Also, without inclusion of an IVD failure model, energy error forced the end of the simulation in flexion-compression. Therefore, inclusion of IVD failure model is important since it leads to realistic results, but the maximal strain failure model is recommended.

Using X-rays in photodynamic therapy: an overview.

Photodynamic therapy is a therapeutic option to treat cancer and other diseases. PDT is used every day in dermatology, and recent developments in the treatment of glioblastoma, mesothelioma or prostate have demonstrated the efficacy of this modality. In order to improve the efficacy of PDT, different strategies are under development, such as the use of targeted PS or nanoparticles to improve selectivity and the design of light devices to better monitor the light dose. Due to the low penetration of light into tissue, another way to improve the efficacy of PDT to treat deep tumors is the use of upconversion NPs or bi-photon absorption compounds. These compounds can be excited in the red part of the spectrum. A relatively new approach, which we will call PDTX, is the use of X-rays instead of UV-visible light for deeper penetration into tissue. The principle of this technique will be described, and the state-of-art literature concerning this modality will be discussed. First, we will focus on various photosensitizers that have been used in combination with X-ray irradiation. To improve the efficacy of this modality, nanoparticles have been designed that allow the conversion of high-energy ionizing radiation into UV-visible light; these are potential candidates for the PDTX approach. They will be discussed at the end of this review.

Head impact in a snowboarding accident.

To effectively prevent sport traumatic brain injury (TBI), means of protection need to be designed and tested in relation to the reality of head impact. This study quantifies head impacts during a typical snowboarding accident to evaluate helmet standards. A snowboarder numerical model was proposed, validated against experimental data, and used to quantify the influence of accident conditions (speed, snow stiffness, morphology, and position) on head impacts (locations, velocities, and accelerations) and injury risk during snowboarding backward falls. Three hundred twenty-four scenarios were simulated: 70% presented a high risk of mild TBI (head peak acceleration >80 g) and 15% presented a high risk of severe TBI (head injury criterion >1000). Snow stiffness, speed, and snowboarder morphology were the main factors influencing head impact metrics. Mean normal head impact speed (28 ± 6 km/h) was higher than equivalent impact speed used in American standard helmet test (ASTM F2040), and mean tangential impact speed, not included in standard tests, was 13.8 (±7 km/h). In 97% of simulated impacts, the peak head acceleration was below 300 g, which is the pass/fail criteria used in standard tests. Results suggest that initial speed, impacted surface, and pass/fail criteria used in helmet standard performance tests do not fully reflect magnitude and variability of snowboarding backward-fall impacts.

Inorganic Nanoparticles for Photodynamic Therapy.

Photodynamic therapy (PDT) is a well-established technique employed to treat aged macular degeneration and certain types of cancer, or to kill microbes by using a photoactivatable molecule (a photosensitizer, PS) combined with light of an appropriate wavelength and oxygen. Many PSs are used against cancer but none of them are highly specific. Moreover, most are hydrophobic, so are poorly soluble in aqueous media. To improve both the transportation of the compounds and the selectivity of the treatment, nanoparticles (NPs) have been designed. Thanks to their small size, these can accumulate in a tumor because of the well-known enhanced permeability effect. By changing the composition of the nanoparticles it is also possible to achieve other goals, such as (1) targeting receptors that are over-expressed on tumoral cells or neovessels, (2) making them able to absorb two photons (upconversion or biphoton), and (3) improving singlet oxygen generation by the surface plasmon resonance effect (gold nanoparticles). In this chapter we describe recent developments with inorganic NPs in the PDT domain. Pertinent examples selected from the literature are used to illustrate advances in the field. We do not consider either polymeric nanoparticles or quantum dots, as these are developed in other chapters.

Biomechanical analysis of fracture risk associated with tibia deformity in children with osteogenesis imperfecta: a finite element analysis.

OBJECTIVES: Osteogenesis imperfecta (OI) frequently leads to long-bone bowing requiring a surgical intervention in severe cases to avoid subsequent fractures. However, there are no objective criteria to decide when to perform such intervention. The objective is to develop a finite element model to predict the risk of tibial fracture associated with tibia deformity in patients with OI. METHODS: A comprehensive FE model of the tibia was adapted to match bi-planar radiographs of a 7 year-old girl with OI. Ten additional models with different deformed geometries (from 2° to 24°) were created and the elasto-plastic mechanical properties were adapted to reflect OI conditions. Loads were obtained from mechanography of two-legged hopping. Two additional impact cases (lateral and torsion) were also simulated. Principal strain levels were used to define a risk criterion. RESULTS: Fracture risks for the two-legged hopping load case remained low and constant until tibia bowing reached 15° and 16° in sagittal and coronal planes respectively. Fracture risks for lateral and torsion impact were equivalent whatever the level of tibial bowing. CONCLUSIONS: The finite element model of OI tibia provides an objective means of assessing the necessity of surgical intervention for a given level of tibia bowing in OI-affected children.

Reactive molecular dynamics of the initial oxidation stages of Ni111 in pure water: effect of an applied electric field.

Corrosion processes occurring in aqueous solutions are critically dependent upon the interaction between the metal electrode and the solvent. In this work, the interaction of a nickel substrate with water molecules has been investigated using reactive force field (ReaxFF) molecular dynamics simulations. This approach was originally developed by van Duin and co-workers to study hydrocarbon chemistry and the catalytic properties of organic compounds. To our knowledge, this method has not previously been used to study the corrosion of nickel. In this work, we studied the interaction of 480 molecules of water (ρ = 0.99 g·cm(-3)) with Ni(111) surfaces at 300 K. The results showed that a water "bilayer" was adsorbed on the nickel surface. In the absence of an applied electric field, no dissociation of water was observed. However, the nickel atoms at the surface were charged positively, whereas the first water layer was charged negatively, indicating the formation of an electric double layer. To study the corrosion of nickel in pure water, we introduced an external electric field between the metal and the solution. The electric field intensity varied between 10 and 20 MeV/cm. The presence of this electric field led to oxidation of the metal surface. The structural and morphological differences associated with the growth of this oxide film in the presence of the electric field were evaluated. The simulated atomic trajectories were used to analyze the atomic displacement during the reactive process. The growth of the oxide scale on the nickel surface was primarily due to the movement of anions toward the interior of the metal substrate and the migration of nickel toward the free surface. We found that increasing the electric field intensity sped up the corrosion of nickel. The results also showed that the oxide film thickness increased linearly with increasing electric field intensity.

Photodynamic molecular beacons triggered by MMP-2 and MMP-9: influence of the distance between photosensitizer and quencher onto photophysical properties and enzymatic activation.

Angiogenesis is a key step in the tumoral progression process. It is characterized by an over-expression of a number of matrix metalloproteinases (MMP). Among these MMPs, gelatinases (MMP-2 and MMP-9) are known to play a critical role in tumor angiogenesis and the growth of many cancers. Photodynamic Molecular Beacons (PMB) can be designed for cancer treatment by associating a chlorin-like photosensitizer and a black hole quencher linked by a gelatinase substrate peptide with the aim of silencing photosensitizer toxicity in non-targeted cells and restore its toxicity only in surrounding gelatinases. This article provides a report on the synthesis and photophysical and biochemical studies of new families of PMB, using tetraphenylchlorin and a black hole quencher as a donor-acceptor pair, and MMP specific sequence (H-Gly-Pro-Leu-Gly-Ile-Ala-Gly-Gln-Lys-OH or H-Pro-Leu-Gly-Leu-OH) to keep them in close proximity. Different spacers were used to evaluate the influence of the distance between the photosensitizer and the quencher on the photophysical properties and enzymatic activation of the PMB. Time-resolved quenching experiments were performed and FRET energy transfer could be observed. Photosensitizers' triplet state band in transient absorption disappears in PMB. However, even if both MMP-2 and MMP-9 were found to efficiently cleave the peptide alone, no cleavage was observed for all PMB. Further studies would be required to assess the ability of the PMB constructs to retain the sensitivity of the peptide linker to be cleaved by matrix metalloproteinases.

Liver injuries in frontal crash situations a coupled numerical - experimental approach.

From clinical knowledge, it has been established that hepatic traumas frequently lead to lethal injuries. In frontal or lateral crash situations, these injuries can be induced by pure deceleration effects or blunt trauma due to belt or steering wheel impact. Concerning the liver under frontal decelerations, how could one investigate organ behaviour leading to the injury mechanisms? This work couples experimental organ decelerations measurements (with 19 tests on cadaver trunks) and finite element simulation, provides a first analysis of the liver behaviour within the abdomen. It shows the influence of the liver attachment system that leads to liver trauma and also torsion effects between the two lobes of the liver. Injury mechanisms were evaluated through the four phases of the liver kinematics under frontal impact: (1) postero-anterior translation, (2) compression and sagittal rotation, (3) rotation in the transverse plane and (4) relaxation.

[Translational research and Cancer Plan]. / Recherche translationnelle et plan Cancer.

The French Cancer Plan 2003-2007 has made translational research central to its research programme, to ensure the care-research continuum and the quickest application possible for the most recent discoveries, for the patients' benefit. This is a new field of research, still little-known or ill-understood. A working group, composed of physicians and researchers from academic research and industrial research, sought to define translational research in cancerology and define the issues at stake in it. Translational research needs to develop in close connection with the patients in order to enable a bi-directional flow of knowledge from cognitive research toward medical applications and from observations made on patients toward cognitive research. Placed under the aegis of the French National Cancer Institute and Leem Research, the group has put forth a strategy for implementing translational research in cancerology in France to make it attractive, competitive and efficient and to foster the development of public-private partnerships.