Influence of bending pre-load on the tensile response of the lumbar spine.

Previous full body cadaver testing has shown that both obliquely oriented seats in survivable aircraft crashes and far-side oblique crashes in vehicles present distinctive occupant kinematics that are not yet well understood. Knowledge surrounding how these loading scenarios affect the lumbar spine is particularly lacking as there exists minimal research concerning oblique loading. The current study was created to evaluate a novel experimental method through comparison with existing literature, and to examine the impact of a static bending pre-load (posture) on the load-displacement response for the whole lumbar spine loaded in non-destructive axial distraction. T12-S1 lumbar spines were tested in tension to 4 mm of displacement while positioned in one of three pre-load postures. These postures were: the spine's natural, unloaded curvature (neutral), flexed forward (flexed), and combined flexion and lateral bending (oblique). Deviations from a neutral spine position were shown to significantly increase peak loads and tensile stiffness. The presence of a flexion pre-load caused statistically significant increases in tensile stiffness, tensile force, and bending moments. The addition of a lateral bending pre-load to an already flexed spine did not significantly alter the tensile response. However, the flexion moment response was significantly affected by the additional postural pre-load. This work indicates that the initial conditions of distraction loading significantly affect lumbar spine load response. Therefore, future testing that seeks to emulate crash dynamics of obliquely seated occupants must account for multi-axis loading.

Evaluation of geometric tortuosity for 3D digitally generated porous media considering the pore size distribution and the A-star algorithm.

Porous materials are of great interest in multiple applications due to their usefulness in energy conversion devices and their ability to modify structural and diffusive properties. Geometric tortuosity plays an important role in characterizing the complexity of a porous medium. The literature on several occasions has related it as a parameter dependent on porosity only. However, due to its direct relationship with the morphology of the medium, a deeper analysis is necessary. For this reason, in the present study, the analysis of the geometric tortuosity is proposed considering the porosity and the pore size distribution. Geometric tortuosity in artificially generated digital porous media is estimated using the A-star algorithm and the Pore Centroid method. By performing changes in the size of the medium and the distribution of the pore size, results are obtained that indicate that the geometric tortuosity does not only depend on the porosity. By maintaining the same porosity, the geometric tortuosity increases if the pore size is reduced. Similarly, these pore size effects are greater if the size of the medium is reduced. The A-star algorithm was found to be more suitable to characterize the majority of paths within the half-pore. On the other hand, to increase the size, the Pore Centroid method is the most appropriate. Finally, three types of correlations were generated relating tortuosity with porosity and pore size. All the correlations were determined with 95% of interval confidence.

A novel posture control device to induce high-rate complex loads for spine biomechanical studies.

Modern environmental scenarios such as autonomous vehicles, aircrafts, and military vehicles position the human body in a nonstandard posture and induce multiplanar loads; however, current spine alignment methods and loading are based on sagittal and planar loads. The objective of this study is to develop a posture control device and demonstrate its ability to induce multiplanar loads to the human cadaver spinal columns. The inferior end of the device was designed to allow a full six degree-of-freedom control for positioning the specimen via a coupled x-y cross table, vertical lift platform, and triaxial rotation mechanism. The superior end of the device was designed such that the cranial fixation of the specimen could be attached to the piston of the electrohydraulic testing apparatus directly or via a rotary disc through a slider-crank mechanism. The former attachment induces complex forces and moments, while the latter induces controlled moments with minimal forces. The usability of the posture control device was demonstrated by conducting experiments with a thoracolumbar spinal column for combined forces and moments, and with a head-neck column for complex moments, and in both cases, the uniaxial travel of the piston was at a dynamic rate. The posture control device can be used to study the biomechanics of the spine under complex loads and with different postures and develop injury criteria for different field environments.

Mapping the kinetic and thermodynamic landscape of formaldehyde oligomerization under neutral conditions.

Density functional theory calculations, including Poisson-Boltzmann implicit solvent and free energy corrections, are applied to study the thermodynamic and kinetic free energy landscape of formaldehyde oligomerization up to the C4 species in aqueous solution at pH 7. Oligomerization via C-O bond formation leads to linear polyoxymethylene (POM) species, which are the most kinetically accessible oligomers and are marginally thermodynamically favored over their oxane ring counterparts. On the other hand, C-C bond formation via aldol reactions leads to sugars that are thermodynamically much more stable in free energy than POM species; however, the barrier to dimerization is very high. Once this initial barrier is traversed, subsequent addition of monomers to generate trimers and tetramers is kinetically more feasible. In the aldol reaction, enolization of the oligomers provides the lowest energy pathway to larger oligomers. Our study provides a baseline free energy map for further study of oligomerization reactions under catalytic conditions, and we discuss how this will lead to a better understanding of complex reaction mixtures with multiple intermediates and products.

Glycolaldehyde monomer and oligomer equilibria in aqueous solution: comparing computational chemistry and NMR data.

A computational protocol utilizing density functional theory calculations, including Poisson-Boltzmann implicit solvent and free energy corrections, is applied to study the thermodynamic and kinetic energy landscape of glycolaldehyde in solution. Comparison is made to NMR measurements of dissolved glycolaldehyde, where the initial dimeric ring structure interconverts among several species before reaching equilibrium where the hydrated monomer is dominant. There is good agreement between computation and experiment for the concentrations of all species in solution at equilibrium, that is, the calculated relative free energies represent the system well. There is also relatively good agreement between the calculated activation barriers and the estimated rate constants for the hydration reaction. The computational approach also predicted that two of the trimers would have a small but appreciable equilibrium concentration (>0.005 M), and this was confirmed by NMR measurements. Our results suggest that while our computational protocol is reasonable and may be applied to quickly map the energy landscape of more complex reactions, knowledge of the caveats and potential errors in this approach need to be taken into account.

PVRL1 variants contribute to non-syndromic cleft lip and palate in multiple populations.

Poliovirus Receptor Like-1 (PVRL1) is a member of the immunoglobulin super family that acts in the initiation and maintenance of epithelial adherens junctions and is mutated in the cleft lip and palate/ectodermal dysplasia 1 syndrome (CLPED1, OMIM #225000). In addition, a common non-sense mutation in PVRL1 was discovered more often among non-syndromic sporadic clefting cases in Northern Venezuela in a previous case-control study. The present work sought to ascertain the role of PVRL1 in the sporadic forms of orofacial clefting in multiple populations. Multiple rare and common variants from all three splice isoforms were initially ascertained by sequencing 92 Iowan and 86 Filipino cases and CEPH controls. Using a family-based analysis to examine these variants, the common glycine allele of the G361V coding variant was significantly overtransmitted among all orofacial clefting phenotypes (P = 0.005). This represented G361V genotyping from over 800 Iowan, Danish, and Filipino families. Among four rare amino acid changes found within the V1 and C1 domains, S112T and T131A were found adjacent to critical amino acid positions within the V1 variable domain, regions previously shown to mediate cell-to-cell and cell-to-virus adhesion. The T131A variant was not found in over 1,300 non-affected control samples although the alanine is found in other species. The serine of the S112T variant position is conserved across all known PVRL1 sequences. Together these data suggest that both rare and common mutations within PVRL1 make a minor contribution to disrupting the initiation and regulation of cell-to-cell adhesion and downstream morphogenesis of the embryonic face.

Candidate genes for oral-facial clefts in Guatemalan families.

Nonsyndromic cleft lip +/- cleft palate (CL/P) is a complex trait of unknown etiology. Most genetic studies of CL/P define affection status in a way that ignores subtle subclinical manifestations, resulting in a potential loss of statistical power. This study investigated 10 candidate genes in 155 individuals from 25 Guatemalan CL/P families. High-resolution ultrasound images of the orbicularis oris (OO) muscle were obtained. CL/P was present in 28 family members; an additional 10 had subcutaneous OO muscle defects. Family-based association studies were performed for both narrow (CL/P only) and broad (CL/P plus OO muscle defects) definitions of affection status. PVRL1 was significantly associated under both definitions (P = 0.04, narrow; P = 0.02, broad). Association with JAG2 improved from P = 0.09 under the narrow definition to P = 0.04 under the broad definition. Broadening the oral-facial cleft phenotype to include subclinical variants may improve power in genetic studies.

Medical sequencing of candidate genes for nonsyndromic cleft lip and palate.

Nonsyndromic or isolated cleft lip with or without cleft palate (CL/P) occurs in wide geographic distribution with an average birth prevalence of 1/700. We used direct sequencing as an approach to study candidate genes for CL/P. We report here the results of sequencing on 20 candidate genes for clefts in 184 cases with CL/P selected with an emphasis on severity and positive family history. Genes were selected based on expression patterns, animal models, and/or role in known human clefting syndromes. For seven genes with identified coding mutations that are potentially etiologic, we performed linkage disequilibrium studies as well in 501 family triads (affected child/mother/father). The recently reported MSX1 P147Q mutation was also studied in an additional 1,098 cleft cases. Selected missense mutations were screened in 1,064 controls from unrelated individuals on the Centre d'Etude du Polymorphisme Humain (CEPH) diversity cell line panel. Our aggregate data suggest that point mutations in these candidate genes are likely to contribute to 6% of isolated clefts, particularly those with more severe phenotypes (bilateral cleft of the lip with cleft palate). Additional cases, possibly due to microdeletions or isodisomy, were also detected and may contribute to clefts as well. Sequence analysis alone suggests that point mutations in FOXE1, GLI2, JAG2, LHX8, MSX1, MSX2, SATB2, SKI, SPRY2, and TBX10 may be rare causes of isolated cleft lip with or without cleft palate, and the linkage disequilibrium data support a larger, as yet unspecified, role for variants in or near MSX2, JAG2, and SKI. This study also illustrates the need to test large numbers of controls to distinguish rare polymorphic variants and prioritize functional studies for rare point mutations.