Enumerating constrained elementary flux vectors of metabolic networks

The concept of elementary vector is generalised to the case where the steady-state space of the metabolic network is not a flux cone but is a general polyhedron due to further inhomogeneous constraints on the flows through some of the reactions. On one hand, this allows to selectively enumerate elementary modes which satisfy certain optimality criteria and this can yield a large computational gain compared with full enumeration. On the other hand, in contrast to the single optimum found by executing a linear program, this enables a comprehensive description of the set of alternate optima often encountered in flux balance analysis. The concepts are illustrated on a metabolic network model of human cardiac mitochondria.

Classification of intervertebral disk degeneration with axial T2 mapping

OBJECTIVE: The aim of this study was to establish an MRI classification system for intervertebral disks using axial T2 mapping, with a special focus on evaluating early degenerative intervertebral disks. MATERIALS AND METHODS: Twenty-nine healthy volunteers (19 men, 10 women; age range, 20-44 years; mean age, 31.8 years) were studied, and axial T2 mapping was performed for the L3-L4, L4-L5, and L5-S1 intervertebral disks. Grading was performed using three classification systems for degenerative disks: our system using axial T2 mapping and two other conventional classification systems that focused on the signal intensity of the nucleus pulposus or the structural morphology in sagittal T2-weighted MR images. We analyzed the relationship between T2, which is known to correlate with change in composition of intervertebral disks, and degenerative grade determined using the three classification systems. RESULTS: With axial T2 mapping, differences in T2 between grades I and II were smaller and those between grades II and III, and between grades III and IV, were larger than those with the other grading systems. The ratio of intervertebral disks classified as grade I was higher with the conventional classification systems than that with axial T2 mapping. In contrast, the ratio of intervertebral disks classified as grade II or III was higher with axial T2 mapping than that with the conventional classification systems. CONCLUSION: Axial T2 mapping provides a more T2-based classification. The new system may be able to detect early degenerative changes before the conventional classification systems can.

Traumatic extra-axial hemorrhage: correlation of postmortem MSCT, MRI, and forensic-pathological findings

PURPOSE: To evaluate the diagnostic accuracy of in situ postmortem multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) in the detection of primary traumatic extra-axial hemorrhage. MATERIALS AND METHODS: Thirty forensic neurotrauma cases and 10 nontraumatic controls who underwent both in situ postmortem cranial MSCT and MR imaging before autopsy were retrospectively reviewed. Both imaging modalities were analyzed in view of their accuracy, sensitivity, and specificity concerning the detection of extra-axial hemorrhage. Statistical significance was calculated using the McNemar test. kappa values for interobserver agreement were calculated for extra-axial hemorrhage types and to quantify the agreement between both modalities as well as MRI, CT, and forensics, respectively. RESULTS: Analysis of the detection of hemorrhagic localizations showed an accuracy, sensitivity, and specificity of 89%, 82%, and 92% using CT, and 90%, 83%, and 94% using MRI, respectively. MRI was more sensitive than CT in the detection of subarachnoid hemorrhagic localizations (P = 0.001), whereas no significant difference resulted from the detection of epidural and subdural hemorrhagic findings (P = 0.248 and P = 0.104, respectively). Interobserver agreement for all extra-axial hemorrhage types was substantial (CT kappa = 0.76; MRI kappa = 0.77). The agreement of both modalitites was almost perfect (readers 1 and 2 kappa = 0.88). CONCLUSION: CT and MRI are of comparable potential as forensic diagnostic tools for traumatic extra-axial hemorrhage. Not only of forensic, but also of clinical interest is the observation that most thin blood layers escape the radiological evaluation.

A patient-specific finite element methodology to predict damage accumulation in vertebral bodies under axial compression, sagittal flexion and combined loads

Due to the inherent limitations of DXA, assessment of the biomechanical properties of vertebral bodies relies increasingly on CT-based finite element (FE) models, but these often use simplistic material behaviour and/or single loading cases. In this study, we applied a novel constitutive law for bone elasticity, plasticity and damage to FE models created from coarsened pQCT images of human vertebrae, and compared vertebral stiffness, strength and damage accumulation for axial compression, anterior flexion and a combination of these two cases. FE axial stiffness and strength correlated with experiments and were linearly related to flexion properties. In all loading modes, damage localised preferentially in the trabecular compartment. Damage for the combined loading was higher than cumulated damage produced by individual compression and flexion. In conclusion, this FE method predicts stiffness and strength of vertebral bodies from CT images with clinical resolution and provides insight into damage accumulation in various loading modes.

Inhibition of FcepsilonRI-dependent mediator release and calcium flux from human mast cells by sialic acid-binding immunoglobulin-like lectin 8 engagement

BACKGROUND: Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of glycan-binding inhibitory receptors, and among them, Siglec-8 is selectively expressed on human eosinophils, basophils, and mast cells. On eosinophils, Siglec-8 engagement induces apoptosis, but its function on mast cells is unknown. OBJECTIVE: We sought to study the effect of Siglec-8 engagement on human mast cell survival and mediator release responses. METHODS: Human mast cells were generated from CD34+ precursors. Apoptosis was studied by using flow cytometry. Mast cell mediator release or human lung airway smooth muscle contraction was initiated by FcepsilonRI cross-linking with or without preincubation with Siglec-8 or control antibodies, and release of mediators was analyzed along with Ca++ flux. RBL-2H3 cells transfected with normal and mutated forms of Siglec-8 were used to study how Siglec-8 engagement alters mediator release. RESULTS: Siglec-8 engagement failed to induce human mast cell apoptosis. However, preincubation with Siglec-8 mAbs significantly (P < .05) inhibited FcepsilonRI-dependent histamine and prostaglandin D(2) release, Ca++ flux, and anti-IgE-evoked contractions of human bronchial rings. In contrast, release of IL-8 was not inhibited. Siglec-8 ligation was also shown to inhibit beta-hexosaminidase release and Ca++ flux triggered through FcepsilonRI in RBL-2H3 cells transfected with full-length human Siglec-8 but not in cells transfected with Siglec-8 containing a tyrosine to phenylalanine point mutation in the membrane-proximal immunoreceptor tyrosine-based inhibitory motif domain. CONCLUSION: These data represent the first reported inhibitory effects of Siglec engagement on human mast cells.