O câncer de mama é o tipo mais freqüente e o segundo mais letal no mundo. Embora ass taxas de sobrevida dos pacientes tenham aumentado consideravelmente nas últimas décadas, indicadores prognósticos desfavoráveis são associados a pacientes com diagnóstico em fase avançada e presença de metástases, frequentemente associadas à existência de células-tronco tumorais (CTT). As CTT são indiferenciadas e capazes de autorrenovação e diferenciação, o que as torna fundamentais para a manutenção da heterogeneidade celular intratumoral. As CTTs são altamente invasivas, tumorigênicas e resistentes a tratamentos convencionais, sendo frequentemente associadas ao surgimento de metástase e recidiva após tratamento. O microambiente tumoral modula as CTT por meio de células e da matriz extracelular (MEC), uma estrutura biologicamente dinâmica, complexa e que regula processos celulares como migração, invasão e diferenciação. A MEC é composta por uma grande variedade de moléculas, peptídeos e macromoléculas, sendo o colágeno seu componente mais abundante. A alta densidade mamográfica é frequentemente associada a elevada rigidez da MEC e deposição aumentada de colágeno fibrilar, principalmente colágeno tipo I (Col I), e é um dos maiores fatores de risco independentes para o desenvolvimento do câncer de mama. A alta densidade de Col I e rigidez da MEC também está associada à maior agressividade tumoral e metástase. Col I também induz o fenótipo tronco tumoral em diversos tipos celulares tumorais, embora o papel da densidade sobre este efeito seja pouco esclarecido. Nosso estudo avaliou a hipótese de a alta densidade de Col I induzir o fenótipo tronco tumoral. Cultivamos linhagens normais (MCF-10A) e tumorais (MDA-MB-231 e MCF-7) de mama em géis de baixa, média e alta densidade de Col I. Também cultivamos células em superfície bidimensional (2D) e em suspensão para geração de mamoesferas (ME), representando o cultivo tradicional e de enriquecimento de CTTs, respectivamente. Avaliamos os níveis do imunofenótipo tronco (CD44+CD24-), expressão gênica e proteica de marcadores de CTTs e de resposta mecânica ao substrato (mecanotransdução), bem como potencial clonogênico, autorrenovação celular e alinhamento fibrilar de géis de Col I. Alta densidade de Col I elevou os níveis da subpopulação CD44+CD24- e inibiu o alongamento celular da linhagem MDA-MB-231, porém não modulou a expressão de marcadores de CTT, bem como potencial clonogênico, autorrenovação celular e alinhamento fibrilar de géis de Col I. A alta densidade de Col I induziu aumento dos níveis totais da isoforma variante da glicoproteína CD44 (CD44v), receptor de estrógeno (RE &#945) e do fator de pluripotência Sox2 em linhagem MCF-7 derivada de ME. Entretanto, os níveis nucleares dos fatores de transcrição (RE &#945 e Sox2) permaneceram inalterados. Em comum, a alta densidade de Col I não elevou os níveis nucleares do mecanotransdutor YAP em linhagens MDAMB-231 e MCF-7 derivada de ME. Concluímos que a alta densidade de Col I induz parcialmente o fenótipo molecular, mas não o funcional, de células tumorais mamárias. / Breast cancer is the most frequent and second deadliest cancer type worldwide. Although patient survival rates have increased considerably in recent decades, unfavorable prognostic indicators are associated with patients with advanced disease stage at diagnosis and presence of metastases, frequently associated with the existence of cancer stem cells (CSC). CSC are undifferentiated and capable of self renewal and differentiation, making them fundamental for the maintenance of intratumoral cellular heterogeneity. CTTs are highly invasive, tumorigenic and resistant to conventional treatments, and are frequently associated with the onset of metastasis and relapse after treatment. The tumor microenvironment modulates CTT by means of cells and the extracellular matrix (ECM), a biologically complex and dynamic structure that regulates cell processes such as migration, invasion and differentiation. ECM is composed of a large variety of molecules, peptides and macromolecules, with collagen being its most abundant component. High mammographic density is often associated with high MEC stiffness and increased deposition of fibrillar collagen, mainly type I collagen (Coll I), and is one of the main independent risk factors for breast câncer development. High Coll I density and ECM stifness are also associated with increased tumor aggressiveness and metastasis. Coll I also induces tumor stemness in several tumor cell types, although the role of its density on this effect is unclear. Our study evaluated the hypothesis that high Coll I density induces the tumor stemness. We cultured normal-like- (MCF-10A) and tumoral (MDA-MB-231 and MCF-7) breast cell lines in low-, medium- and high-density Coll I gels. We also cultured cells in twodimensional (2D) surface and in suspension for the generation of mammospheres (MS), representing the traditional cell culture and CSC enrichment, respectively. We evaluated the levels of the CSC immunophenotype (CD44+CD24), gene/protein expression of CSC markers and mechanical response to the substrate (mechanotransduction), as well as the clonogenic potential, cell self-renewal and fibrillar alignment of Col I gels. High Coll I density increased the levels of the CD44+CD24- subpopulation and inhibited cell elongation of the MDA-MB-231 cell line, but did not modulate the expression of CSC markers as well as clonogenic potential, cell self-renewal and fibrillar alignment of Col I gels. High Coll I density increased total levels of the variant CD44 glycoprotein (CD44v), estrogen receptor (ER) and the pluripotency factor Sox2 in MS-derived MCF-7. However, the nuclear levels of the transcription factors (ER &#945 and Sox2) remained unchanged. In common, high Coll I density did not increase nuclear levels of the mechanotransducer YAP in MDA-MB- 231 and MS-derived cell lines. We conclude that high Coll I density partially induces the molecular stemness, but not the functional, phenotype of mammary tumor cells.

The objectives of this research were 1) to examine correlations between compositional and structural properties of emulsion-treated base (ETB) layers, determine which of these factors exhibit the greatest spatial variability, and determine if significant differences exist between different test sections on a given project and 2) to investigate temporal trends in the structural properties of base materials treated with asphalt emulsion and to assess the rate at which ETB design properties are achieved. The research conducted in this study focused on testing of the ETB layer constructed on 7800 South (SR-48) in West Jordan, Utah. The research conducted in this study involved field and laboratory evaluations of spatial and temporal variability in properties of ETB. Regarding spatial results, the average modulus values of the ETB layer were unusually low for a typical stabilized base material and were in general even lower than the subgrade modulus values at this test site. All three sections had high moisture contents after compaction, with the moisture content of the ETB layer exceeding the specified optimum moisture content at many locations even before the emulsion was injected. One of the three test sections had higher percentages of reclaimed asphalt pavement and emulsion than the other two. The ETB compressive strength was very low throughout the entire year of testing, clearly demonstrating the consequences of inadequate emulsion curing associated with this project. The statistical analyses showed that higher pre-treatment moisture contents and higher amounts of binder added were associated with lower stiffness and strength, while higher wet densities were associated with higher stiffness and strength. The analyses also showed substantial variation in most response variables but comparatively low variation in predictor variables. Only four structural properties were significantly different between sections. Temporal testing was performed to monitor the properties of the ETB layer and to compare the ETB section to an adjacent untreated base course (UTBC) section. The ETB moisture content did not change significantly during the 1-year monitoring period, showing that drying of the ETB layer did not occur following placement of the hot mix asphalt surface. Furthermore, the analyses provided no evidence that the ETB layer experienced any sustained increase in strength as a result of emulsion curing; instead, the ETB modulus was shown to be greatly dependent on season, with higher ETB moisture contents and temperatures corresponding to lower ETB modulus values. Even during the winter when the ETB stiffness reached its peak, the modulus was still below the target value specified for this project. The statistical analyses indicated that the modulus values of the ETB and UTBC layers were not statistically different.

<p>Fibre-to-board is a simulation model developed at Stora Enso Research Centre Karlstad. Within this model isotropic hand sheet properties are used as input data for prediction of the final multi ply board properties. In order to improve and verify the calculations from simulations in Fibre-to-board so that these will correspond better with the results from the measurements on the paper/board machine, it was requested at RCK to investigate the possibility to optimize the input data to the model.</p><p>Standardized hand sheet forming always results in sheets with properties far away from those produced on a machine. Therefore the aim with this Master thesis was to modify the laboratory procedure to receive hand sheets with properties closer to machine sheets. To achieve this, it was investigated how different parameters affect the sheet properties and if the hand sheet making process could be improved.</p><p>When freely dried sheets were investigated it was found that sheets pressed with a wire clothing between the blotting paper and the hand sheet were less cockled than sheets pressed against only blotting papers. These sheets also tend to have a higher density. The cockling i.e. as a result from shrinkage was also reduced when the sheets were dried between slightly weighted wire clothing. Neither wire clothing nor orientated blotting papers during pressing eliminate the influence of anisotropic blotters on the shrinkage for isotropic hand sheets.</p><p>It was also examined how the fine material influences sheet properties. The results showed that an increase in fines content result in higher shrinkage, higher density, increased TSI, more cockling and decreased air permeability.</p><p>Different pressing loads and an increased density did not have much influence on the shrinkage. The density for freely dried sheets increased with higher load, but the results did not reach machine sheet densities, when the laboratory platen press was used. It might be difficult to receive freely dried hand sheets with higher densities. This is because fibres in freely dried sheets tend to relax after pressing, which will influence the density. Another press than the platen press used in these studies might compensate this matter. An increased pressing load resulted in less cockled sheets.</p><p>The basis weight did not seem to have that large affect on the shrinkage when using machine chest furnish, therefore the basis weight on hand sheets used as input data to the simulation model Fibre-to-board might not be that important.</p><p>It was studied how different plies and SW/CTMP pulp in a mixture affect the shrinkage. The results showed that the shrinkage increased with a higher SW content. It was also found that there is a linear relation between the total shrinkage of a SW/CTMP pulp mixture and the shrinkage for each individual pulp.</p><p>In order to verify the Fibre-to-board model a simulation finally was performed. Furnishes and CD profiles of board were collected from a particular board machine within the Stora Enso Group. Properties from hand sheets made of furnishes were used as input data and the machine CD profiles were used as references. The CD TSI value corresponded with the value received from measurements on the machine board, but the MD TSI value did not. The shrinkage calculated on machine sheets did not coincide with the shrinkage from the simulation in Fibre-to-board.</p><p>There are insecurities in the results from shrinkage measurement on the board CD profile due to the lack of width measurement during the process, which complicates the validation of the Fibre-to-board model.</p> / <p>Fibre to board är en simulerings modell framtagen vid Stora Enso Research Centre Karlstad. Modellen används för att prediktera krympning och styrkeegenskaper hos en bestämd kartongbana. Indata till modellen hämtas ifrån isotropa laboratorieark. För att förbättra och verifiera erhållna resultat från simuleringsmodellen så att de korresponderar bättre med värden från kartongmaskinen fanns det ett önskemål från RCK om att undersöka möjligheten att optimera indata till modellen.</p><p>Laboratoriearktillverkning enligt standard resulterar alltid i ark med egenskaper som ligger långt från maskin arkens. Därför är syftet med detta examensarbete att modifiera arktillverkningsmetoden så att laboratorieark med egenskaper närmare de för maskinark kan erhållas. För att lyckas med detta undersöktes det hur olika parametrar påverkar pappersegenskaperna och om tillverkningsmetoden kunde förbättras.</p><p>Vid undersökning av fritorkade ark upptäcktes att ark som pressats med viraduk mellan läskark och laboratorieark blev mindre buckliga än ark som pressats med enbart läskark. Dessa ark hade också en något högre densitet. Buckligheten som är en följd av krympningen reducerades också när arken torkades mellan viraduk under lätt belastning. Läskarkens inverkan på de isotropa arken kunde inte elimineras genom att använda viraduk vid pressning, inte heller genom att växla läskarken så att deras MD riktning orienterades olika.</p><p>Även finmaterialets inverkan på pappersegenskaperna undersöktes. Resultaten visade att ett ökat finmaterial innehåll ger ökad krympning, högre densitet, ökat dragstyvhetsindex, buckligare ark och en minskad luft permeabilitet.</p><p>Det visade sig att olika presstryck ger arken en högre densitet men krympningen påverkades inte märkbart. Densitet i samma nivå som på maskinark kunde däremot inte erhållas med laboratorieplanpress. Detta kan bero på att fibrerna i fritorkade ark relaxerar efter pressning, vilket ger en lägre densitet. För att kunna få högre densitet kanske en annan press än den planpress som användes i dessa studier kan införas. Det kunde även konstateras att ett ökat presstryck ger mindre buckliga ark.</p><p>I dessa studier, där ark tillverkades av färdiga skiktblandningar från maskinkar, hade inte ytvikten på arken någon större inverkan på krympningen. Detta tyder på att ytvikten på arken som används som indata inte har så stor inverkan vid simulering i modellen Fibre-to-board.</p><p>Det undersöktes även hur skikten i ett två-skikts ark och en blandning av LF/CTMP massa påverkar krympningen. Resultaten visade att krympningen ökar med en högre andel LF och att det finns ett linjärt samband mellan den totala krympningen för en blandning av LF/CTMP massa och krympningen för de enskilda massorna.</p><p>För att kunna verifiera beräkningsmodellen Fibre-to-board utfördes slutligen en simulering. Skiktblandningar och tvärsprofiler från kartong togs ut från en specifik pappers maskin inom Stora Enso koncernen. Egenskaperna på laboratorieark gjorda av skiktblandningarna användes som indata till simuleringsprogrammet och kartongprofilerna från pappersmaskinen användes som referens. Dragstyvhetsindex i CD stämde bra överens med de mätningar som gjordes på maskinarken, men dragstyvhetsindex i MD skiljde sig. Krympningen som beräknades på maskinarken överensstämde inte med det simulerade resultatet. Det förekommer en osäkerhet i krympmätningarna som gjordes på kartong profilerna, då det idag inte förekommer någon mätutrustning på pappersmaskinen, som bestämmer bredden mellan press- och torkpartiet. Detta komplicerar valideringen av Fibre-to-board modellen.</p>

Fracture of the distal radius is one of the most frequent injuries, and it represents about 20% of all adults taken into emergency rooms. A number of studies suggest various methods to reduce the dislocation and to secure fragments of the distal radius. In this study, the Non-Bridging External Wrist Fixator System (NBX), a pre-market-released product manufactured by NUTEK Inc. was biomechanically assessed by comparing with the Universal Distal Radius System (Volar Plate Fixator: VPF), a market-released product manufactured by Stryker Co. The comparison was performed in several parameters, which were wrist motion, radial tilt angle, radial length, volar tilt angle, stiffness, and failure load. Five pairs of fresh human cadaver arms were used for this study. The wrists were tested to obtain x-ray images for 1 normal and 2 injury conditions (intact, fractured, and fixed), 2 load conditions (gravity only and torque applied), and 4 postural conditions (volar flexion, dorsiflexion, ulnar deviation, and radial deviation). These tests yielded 24 (3×2×4) x-ray images for each wrist, and the images were analyzed to obtain the data for each parameter. Although the results were not statistically significant in some conditions, NBX fixation limited wrist motion more than VPF fixation. This result can be explained not only by the difference in the ability of fixation, but also by the difference in the surgical trauma (NBX is less invasive than VPF). Furthermore, in the measurement of radial tilt angle, radial length, and volar tilt angle, NBX was more effective than VPF to reduce and secure the bone fragments of the distal radius. In destructive test, the NBX is less strong than VPF. However, NBX is strong enough to sustain the expected forces of daily activity.

This work aims at enhancing the understanding and to provideimproved models of the dynamic behavior of rubber vibrationisolators which are widely used in mechanical systems.Initially, a time domainmodel relating compressions tocomponent forces accounting for preload effects, frequency anddynamic amplitude dependence is presented. The problem ofsimultaneously modelling the elastic, viscoelastic and frictionforces are removed by additively splitting them, where theelastic force response is modelled either by a fully linear ora nonlinear shape factor based approach, displaying resultsthat agree with those of a neo-Hookean hyperelastic isolatorunder a long term precompression. The viscoelastic force ismodelled by a fractional derivative element, while the frictionforce governs from a generalized friction element displaying asmoothed Coulomb force. This is a versatile one-dimensionalcomponent model effectively using a small number of parameterswhile exhibiting a good resemblance to measured isolatorcharacteristics. Additionally, the nonlinear excitationeffects on dynamic stiffness and damping of a filled rubberisolator are investigated through measurements. It is shownthat the well-known Payne effect - where stiffness is high forsmall excitation amplitudes and low for large amplitudes whiledamping displays a maximum at intermediate amplitudes -evaluated at a certain frequency, is to a large extentinfluenced by the existence of additional frequency componentsin the signal. Finally, a frequency, temperature and preloaddependent dynamic stiffness model is presented covering theranges from 20 to 20 000 Hz, -50 to +50 °C at 0 to 20 %precompression. A nearly incompressible, thermo-rheologicallysimple material model is adopted displaying viscoelasticitythrough a time - strain separable relaxation tensor with asingle Mittag-Leffler function embodying its time dependence.This fractional derivative based function successfully fitsmaterial properties throughout the whole audible frequencyrange. An extended neo-Hookean strain energy function, beingdirectly proportional to the temperature and density, isapplied for the finite deformation response with componentproperties solved by a nonlinear finite element procedure. Thepresented work is thus believed to enlighten workingconditions’impact on the dynamic properties of rubbervibration isolators, while additionally taking some of thesemost important features into account in the presentedmodels.

Continental glaciers covered as much as thirty percent of the present-day inhabited earth during the Quaternary period. Traditionally, one-dimensional consolidation has been considered as the main process of formation for the soils deposited during glaciation. One of the outcomes of accepting one-dimensional consolidation as the main process of formation is that the geomechanical properties of soil in a horizontal plane are isotropic (known as cross-anisotropy). Recent measurements of subglacial pore pressure and preconsolidation pressure profile have indicated that this might not be the case. The role of subglacial shear action has probably been long neglected. The main objective of this research is to investigate the effects of subglacial shearing on the geomechanical properties of glaciated soils. <p> Recent research has found evidence of horizontal property anisotropy associated with the direction of the ice-sheet movement. A testing program was thus proposed to explore the relationship between the anisotropy of property and the direction of past glacier movement. The program involves several fundamental engineering parameters of soils. These parameters together with the corresponding test methods are as follows: (i) Conventional oedometer test yield stress anisotropy; (ii) Oedometer test with lateral stress measurement stiffness anisotropy; (iii) Load cell pressuremeter (LCPM) test in situ stress anisotropy. <p> The physical meaning of yield stress determined by conventional oedometer tests was interpreted as the critical state of structural collapse. The literature review and an experimental study on kaolin samples with a known stress history suggested that yield stress possesses certain dependency on the sampling direction. The anisotropy of yield stress for Battleford till from Birsay, Saskatchewan was also explored by testing directional oedometer samples. In addition, the anisotropy of stiffness was also investigated using a newly developed lateral stress oedometer that is capable of independent measurement of horizontal stresses at three different points with angles of 120 degrees. Preliminary evidence of a correlation between the direction of maximum stiffness in a horizontal plane and the known direction of glacial shear was observed. The correlation between the direction of maximum yield stress and known direction of glaciation was rather poor. Anisotropy of in situ stresses was investigated by conducting LCPM tests in Pot clay in the Netherlands. Based on the LCPM test results, it was concluded that the evidence of a correlation between the anisotropy of in situ stress and known direction of glacial advance is still rather obscure. <p> Although both the laboratory studies and field studies cannot sufficiently confirm the existence of lateral anisotropy of geomechanical properties and its relationship to the direction of the Quaternary ice-sheet movement, the effects of subglacial shearing should not be neglected in assessing the geotechnical properties of glaciated soils. In practice, it is usually found that the preconsolidation pressure profile does not follow the gravitational line as predicted by the one-dimensional consolidation theory and its magnitude is not compatible with the measured effective pressure values at the base of the glacier. It has been suggested that changes in seepage gradient (upward or downward) are responsible for the deviation of preconsolidation pressure profile away from the gravitational line. In this thesis, a new glacial process model consolidation coupled shearing was proposed. This model is based on the framework of traditional soil mechanics (critical state theory, Modified Cam-clay model and one-dimensional consolidation theory) and is consistent with the general geological and glaciological evidences. This model may provide an alternative explanation for the preconsolidation pressure patterns generally observed in practice. It can also be combined with groundwater flow characteristics to explain the diversity of the preconsolidation consolidation patterns. The proposed model was used successfully to obtain the preconsolidation pressure profile observed in Battleford till at Birsay and the subglacial shear-softening phenomenon.

Current design of cemented paste backfill (CPB) barricades tends to be of unknown conservativeness due to limited understanding of their behaviour. Previous work done to characterize barricade response has not accounted for the effects of the surrounding rock stiffness, which can have significant impact on the development of axial forces which enhance capacity via compressive membrane action. Parametric analyses were performed with the finite element analysis program Augustus-2 to determine the effects of various material and geometric properties on barricade capacity. Equations based on Timoshenko and Boussinesq solutions were developed to model rock stiffness effects based on boundary material properties. An iterative simulation process was used to account for secondary moment effects as a proof of concept. It was found that, for a range of typical rock types, barricade capacity varied significantly. The commonly made design assumption of a fully rigid boundary resulted in unconservative overpredictions of strength.

Current design of cemented paste backfill (CPB) barricades tends to be of unknown conservativeness due to limited understanding of their behaviour. Previous work done to characterize barricade response has not accounted for the effects of the surrounding rock stiffness, which can have significant impact on the development of axial forces which enhance capacity via compressive membrane action. Parametric analyses were performed with the finite element analysis program Augustus-2 to determine the effects of various material and geometric properties on barricade capacity. Equations based on Timoshenko and Boussinesq solutions were developed to model rock stiffness effects based on boundary material properties. An iterative simulation process was used to account for secondary moment effects as a proof of concept. It was found that, for a range of typical rock types, barricade capacity varied significantly. The commonly made design assumption of a fully rigid boundary resulted in unconservative overpredictions of strength.

Gas bearings in oil-free micro-turbomachinery for process gas applications and for power generation (< 400 kW) must offer adequate load capacity and thermal stability, reliable rotordynamic performance at high speeds and temperatures, low power losses and minimal maintenance costs. The metal mesh foil bearing (MMFB) is a promising foil bearing technology offering inexpensive manufacturing cost, large inherent material energy dissipation mechanism, and custom-tailored stiffness and damping properties. This dissertation presents predictions and measurements of the dynamic forced performance of various high speed and high temperature MMFBs. MMFB forced performance depends mainly on its elastic support structure, consisting of arcuate metal mesh pads and a smooth top foil. The analysis models the top foil as a 2D finite element (FE) shell supported uniformly by a metal mesh under-layer. The solution of the structural FE model coupled with a gas film model, governed by the Reynolds equation, delivers the pressure distribution over the top foil and thus the load reaction. A perturbation analysis further renders the dynamic stiffness and damping coefficients for the bearing. The static and dynamic performance predictions are validated against limited published experimental data. A one-to-one comparison of the static and dynamic forced performance characteristics of a MMFB against a Generation I bump foil bearing (BFB) of similar size, with a slenderness ratio L/D=1.04, showcases the comparative performance of MMFB against a commercially available gas foil bearing design. The measurements of rotor lift-off speed and drag friction at start-up and airborne conditions are conducted for rotor speeds up to 70 krpm and under identical specific loads (W/LD =0.06 to 0.26 bar). The dynamic force coefficients of the bearings are estimated, in a ‘floating bearing’ type test rig, while floating atop a journal spinning to speeds as high as 50 krpm and with controlled static loads (22 N) applied in the vertical direction. The parameter identification is conducted in the frequency range of 200-400 Hz first, and then up to 600 Hz using higher load capacity shakers. A finite element rotordynamic program (XLTRC2) models a hollow rotor and two MMFBs supporting it and predict the synchronous rotor response for known imbalances. The predictions agree well with the ambient temperature rotor response measurements. Extensive rotor response measurements and rotor and bearing temperature measurements, with a coil heater warming up to 200 ºC and placed inside the hollow rotor, reveal the importance of adequate thermal management. The database of high speed high temperature performance measurements and the development of a predictive tool will aid in the design and deployment of MMFBs in commercial high-speed turbomachinery. The work presented in the dissertation is a cornerstone for future analytical developments and further testing of practical MMFBs.

There are several reasons to research the effects of axial twist exposures and the resulting loading on the spine. The lack of consensus from the limited work that has previously examined the role of axial twist moments and motions in the development of spine injuries or generation of low back pain is the primary reason. From recently published works, axial twist moments appear to represent an increased risk for injury development when it acts in concert with loading about other physiological axes (i.e. flexion, extension, and compression). However, there is a large body of epidemiologic data identifying axial twist moments and/or motion as risk factors for low back disorders and pain, demonstrating the need for this series of investigations. It is likely that these combined exposures increase risk through altering the spine’s load distribution (passive resistance) by modifying the mechanics, but this deduction and related causal mechanism need to be researched. The global objective of this research was focused on determining whether there is evidence to support altered load distribution in the spine, specifically between the intervertebral disc and facets, in response to applied axial twist moments (when added in combination with one and two axes of additional loading). Also included was whether these modes of loading can modify spine mechanics and contribute and/or alter the development of damage and pain. This objective was addressed through one in-vivo (Drake and Callaghan, 2008a– Chapter #2) and three in-vitro (Drake et al., 2008– Chapter #4; Drake and Callaghan, 2008b– Chapter #5; Drake and Callaghan, 2008c– Chapter #6) studies that: (1) Quantified the amount of passive twist motion in the lumbar spine when coupled with various flexion-extension postures; (2) Documented the effects of flexion-extension postures and loading history on the distance between the facet articular surfaces; (3) Evaluated the result of axial twist rotation rates on acute failure of the spine in a neutral flexion posture; and (4) Explored whether repetitive combined loading has the ability to cause enough deformation to the spine to generate pain. Through the combination of findings previously reported in the literature and the outcomes of Drake and Callaghan (2008a– Chapter #2) and Drake et al. (2008– Chapter #4), a postural mediated mechanism was hypothesized to be responsible for governing the load distribution between the facet joints and other structures of the spine (i.e. disc, ligaments). Increased flexed postures were found to decrease the rotational stiffness by resulting in larger twist angles for the same applied twist moment in-vivo relative to a neutral flexion posture (Drake and Callaghan, 2008a– Chapter #2). This suggested there might be an increased load on the disc due to a change in facet coupling in these combined postures. Similarly, increased angles were observed in flexed and twisted postures for in-vitro specimens relative to a neutral flexion posture. These observed differences were found to correspond with altered facet joint mechanics. Specifically that flexed twisted postures increased the inter-facet spacing relative to the initial state of facet articulation (Drake et al., 2008– Chapter #4). These finding supported the postulated postural mechanism. Therefore, in a neutral posture the facet joints likely resisted the majority of any applied twist moment based on the limited range of motion and higher axial rotational stiffness responses observed. It was suspected that the changes in mechanics would likely cause a change in the load distribution however the magnitude of change in load distribution remains to be quantified. Further support for this postulated postural mechanism comes from the mode of failure for specimens that were exposed to 10,000 cycles of 5° axial twist rotation while in a static flexed posture (Drake and Callaghan, 2008c– Chapter #6), and neutrally flexed specimens exposed to 1.5° of rotation for 10,000 cycles reported in the literature. Without flexion, the failure patterns were reported to occur in the endplates, facets, laminae and capsular ligaments, but not the disc. However, with flexion the repetitive axial twist rotational displacements caused damage primarily to the disc. If the load distribution was unchanged, the higher axial rotation angle should have caused the specimen to fail in less cycles of loading, and the failure pattern should not have changed. Modulators of this hypothesized mechanism include the velocity of the applied twist moment and the effects these have on the failure parameters and injury outcomes. The three physiologic loading rates investigated in this work were not shown to affect the ultimate axial twist rotational failure angle or moment in a neutral flexion/extension posture, but were shown to modify flexion-extension stiffness (Drake and Callaghan, 2008b– Chapter #5). All of the flexion-extension stiffness values post failure, from a one-time axial twist exposure, was less than those from a repetitive combined loading exposure that has been established to damage the intervertebral disc but not the facets. Therefore, it is likely that the facet joint provides the primary resistance to acute axial twist moments when the spine is in a neutral flexion posture, but there appears to be a redistribution of the applied load from the facets to the disc in repetitive exposures. The aforementioned studies determined there are changes in load distribution and load response caused by altered mechanics resulting from twist loading, but whether the exposures could possibly produce pain needed to be addressed. Previous research has determined that the disc has relatively low innervation in comparison to the richly innervated facet capsule and vertebra, with only the outer regions being innervated. Likewise, it is assumed that pain could be directly generated as the nucleus pulposus disrupted the innervated outer annular fibres in the process of herniation. Also, direct compression of the spinal cord or nerve roots has been shown to occur from the extruded nucleus and result in the generation of pain responses. Additionally, the nucleus pulposus has been shown to be a noxious stimulus that damages the function and structure of nerves on contact. The other source of nerve root compression commonly recognized is a decrease in intervertebral foramina space, which was previously believed to only be caused through losses in disc height. However, decreased intervertebral foramina space due to repetitive motions appears to be a viable pain generating pathway that may not directly correspond to simply a loss of specimen or disc height (Drake and Callaghan, 2008c– Chapter #6). This is new evidence for combined loading to generate pain through spinal deformation. The objective of many traditional treatments for nerve root compression focus on restoring lost disc height to remove the nerve root compression. Unfortunately, nerve root compression caused by repetitive loading may not be alleviated through this approach. This collection of studies was focused on determining whether altered load distribution in the spine, specifically between the intervertebral disc and facets, in response to applied axial twist loading (when added in combination with one and two axes of additional loading) was occurring, and examining how these modes of loading can contribute and/or alter the development of injury and pain. Therefore, findings generated from this thesis may have important implications for clinicians, researchers, and ergonomists.