BIOMECHANICS AND RELAXIVITY FOR FUNCTIONAL IMAGING OF ARTICULAR CARTILAGE INJURY AND DEGRADATION

Osteoarthritis (OA) is a major debilitating health concern and economic burden worldwide, affecting 27 million people in the United States alone. OA often follows tissue injury, and is marked by changes in the structure and biomechanical function of cartilage, including breakdown of extracellular matrix molecules, loss of bulk tissue stiffness, and increase in articular surface friction and wear. Unlike bone and many other tissues, cartilage lacks an intrinsic capacity for regeneration. Advanced OA is typically diagnosed by patient symptoms (e.g. joint pain) and confirmed by radiographic evaluation of joint space narrowing. However, the application of functional imaging to assess cartilage physiology may provide an early diagnosis of joint changes prior to patient symptoms. One such functional imaging modality, magnetic resonance imaging (MRI), may be used to characterize the mechanics of joint cartilage in vitro and in vivo, but it has not yet been applied to evaluate cartilage injury in defined damage models. Here, we studied the changes in MRI-assessed intratissue strain following cartilage injury, and correlate those changes with traditional assessment metrics such as relaxivity, biochemical composition, and microstructure. Osteochondral samples were harvested from the load-bearing region of juvenile bovine knees. Samples were exposed to injurious compressive loading at 100% strain/second and incubated over four weeks. Tissue strain throughout the cartilage interior was measured by displacements under applied loading by MRI (dualMRI) and coregistered to relaxivity measures of T1 and T2. Proteoglycan and collagen content, cartilage microstructure, and cell viability were also assessed by biochemical, histochemical, and microscopy assays. Injurious compressive strain magnitudes of 50% resulted in decreased chondrocyte viability. By three weeks post-injury, dualMRI strains in the compressive loading direction of injured cartilage increased compared to controls, suggesting a regional loss of tissue stiffness. T2 and sample height increased with incubation time. Changes in proteoglycan and collagen content, and microstructure, were also observed to change with incubation time. These finding indicate that dualMRI may be a promising technology to detect and diagnose the early onset of injury-related degeneration compared to conventional techniques like MR relaxivity. The results also indicate the utility and potential for functional imaging to assess disease progression and treatment

Elaboration et caractérisation d’une mousse métallique

Cette étude est consacrée à l'élaboration par infiltration d'une mousse métallique en aluminium à cellules ouvertes. Les propriétés métallurgiques (macrostructures, mécaniques) et énergétiques (performances de transfert de chaleur) ont été étudiées. Le transfert de chaleur a été étudié numériquement et expérimentalement. Les résultats obtenus ont montre l'effet de la taille des cellules (pores) sur les propriétés mécaniques et énergétiques du matériau fabriqué

Factors Controlling Structural and Floristic Variation of Riparian Zones in a Mountainous Landscape of the Western United States

We examined landscape patterns in the physical conditions and vegetative composition of montane riparian zones to identify their most important sources of variation. Information on plant species cover and on physical characteristics that occur at coarse, medium, and fine scales was collected for 144 riparian plots located throughout the Lake Tahoe Basin, which straddles the California-Nevada border in the western United States. Constrained and unconstrained ordination analyses were used to identify the most important correlates of physical form and plant species composition. Through multivariate analysis of environmental variables (principal components analysis), vegetation data (detrended correspondence analysis), and the combined relationship between the environmental and vegetation data (canonical correspondence analysis), we consistently found that the greatest variation occurred along a gradient of decreasing valley width, decreasing stream sinuosity, and increasing stream slope. Although surface characteristics reflected a 2nd important source of variation in physical conditions, plant species distribution was not strongly correlated with riparian surface conditions. Strong correlations among physical variables that occur at different scales, such as between valley form and geofluvial surface and between geofluvial surface and surface conditions, support the use of a physically based hierarchical framework for organizing riparian zones within the landscape. Such a hierarchical framework would be useful for interpreting patterns in riparian structure and process at different scales and could be applied to riparian zones in other mountain landscapes of the western United States and elsewhere. Moreover, our finding that riparian plant species composition is most strongly correlated with environmental variables that occur at coarse to moderate scales, most of which can be derived from existing data, supports the idea that modeling montane riparian community distribution using topographic and remotely sensed data could be useful; however, a large degree of species variation, unexplained by the variables we collected, indicates that other variables, perhaps disturbance regime, should be included in such a venture

Using Field Data to Assess Model Predictions of Surface and Ground Fuel Consumption by Wildfire in Coniferous Forests of California

Inventories of greenhouse gas (GHG) emissions from wildfire provide essential information to the state of California, USA, and other governments that have enacted emission reductions. Wildfires can release a substantial amount of GHGs and other compounds to the atmosphere, so recent increases in fire activity may be increasing GHG emissions. Quantifying wildfire emissions however can be difficult due to inherent variability in fuel loads and consumption and a lack of field data of fuel consumption by wildfire. We compare a unique set of fuel data collected immediately before and after six wildfires in coniferous forests of California to fuel consumption predictions of the first-order fire effects model (FOFEM), based on two different available fuel characterizations. We found strong regional differences in the performance of different fuel characterizations, with FOFEM overestimating the fuel consumption to a greater extent in the Klamath Mountains than in the Sierra Nevada. Inaccurate fuel load inputs caused the largest differences between predicted and observed fuel consumption. Fuel classifications tended to overestimate duff load and underestimate litter load, leading to differences in predicted emissions for some pollutants. When considering total ground and surface fuels, modeled consumption was fairly accurate on average, although the range of error in estimates of plot level consumption was very large. These results highlight the importance of fuel load input to the accuracy of modeled fuel consumption and GHG emissions from wildfires in coniferous forests

Biomass and Burning Characteristics of Sugar Pine Cones

We investigated the physical and burning characteristics of sugar pine (Pinus lambertiana Douglas) cones and their contribution to woody surface fuel loadings. Field sampling was conducted at the Yosemite Forest Dynamics Plot (YFDP), a 25.6 ha mapped study plot in Yosemite National Park, California, USA. We developed a classification system to describe sugar pine cones of different sizes and decay conditions, and examined differences among cone classes in biomass, bulk density, flame length, burning time, consumption, and relative contribution to surface fuel loads. Sugar pine cones comprised 601 kg ha-1 of surface fuels. Mature cones comprised 54% of cone biomass, and aborted juvenile cones accounted for 44%. Cone biomass, diameter, and bulk density differed among cone condition classes, as did burning characteristics (one-way ANOVA, P \u3c 0.001 in all cases). Flame lengths ranged from 5 cm to 94 cm for juvenile cones, and 71 cm to 150 cm for mature cones. Our results showed that the developmental stage at which sugar pine cones become surface fuels determines their potential contribution to surface fire behavior in Sierra Nevada mixed-conifer forests. Sugar pine cones burn with greater flame lengths and flame times than the cones of other North American fire-tolerant pine species studied to date, indicating that cones augment the surface fire regime of sugar pine forests, and likely do so to a greater degree than do cones of other pine species

Functional Improvement of Regulatory T Cells From Rheumatoid Arthritis Subjects Induced by Capsular Polysaccharide Glucuronoxylomannogalactan

Objective: Regulatory T cells (Treg) play a critical role in the prevention of autoimmunity, and the suppressive activity of these cells is impaired in rheumatoid arthritis (RA). The aim of the present study was to investigate function and properties of Treg of RA patients in response to purified polysaccharide glucuronoxylomannogalactan (GXMGal). Methods: Flow cytometry and western blot analysis were used to investigate the frequency, function and properties of Treg cells. Results: GXMGal was able to: i) induce strong increase of FOXP3 on CD4+ T cells without affecting the number of CD4+CD25+FOXP3+ Treg cells with parallel increase in the percentage of non-conventional CD4+CD25-FOXP3+ Treg cells; ii) increase intracellular levels of TGF-beta1 in CD4+CD25-FOXP3+ Treg cells and of IL-10 in both CD4+CD25+FOXP3+ and CD4+CD25-FOXP3+ Treg cells; iii) enhance the suppressive activity of CD4+CD25+FOXP3+ and CD4+CD25-FOXP3+ Treg cells in terms of inhibition of effector T cell activity and increased secretion of IL-10; iv) decrease Th1 response as demonstrated by inhibition of T-bet activation and down-regulation of IFN-gamma and IL-12p70 production; v) decrease Th17 differentiation by down-regulating pSTAT3 activation and IL-17A, IL-23, IL-21, IL-22 and IL-6 production. Conclusion: These data show that GXMGal improves Treg functions and increases the number and function of CD4+CD25-FOXP3+ Treg cells of RA patients. It is suggested that GXMGal may be potentially useful for restoring impaired Treg functions in autoimmune disorders and for developing Treg cell-based strategies for the treatment of these diseases

Magneto‐structural studies of paramagnetic metal cages

A central concern within the field of molecular magnetism has been the elucidation of magneto-structural correlations. This thesis describes a variety of systems and endeavours to study the relationship between structure and magnetic properties in these systems. The first body of work (chapters 2 and 3) studies CrIII dimers, with the metal centres displaying a dialkoxo bridging moiety and latterly an additional carboxylate bridge to direct the synthesis of ferromagnetic analogues. The second section of work (chapters 4‐6) moves forward to the study of larger, heterometallic 3d‐3d compounds, through the synthesis of a large family of Anderson type MIII 2MII 5 wheels and a subsequent family of (VIVO)2MII 5 wheels. Chapter 2 describes a series of di‐alkoxo bridged Cr(III) dimers, synthesised using the pyridine alcohol ligands 2‐pyridinemethanol (hmpH) and 2‐pyridineethanol (hepH) as well as 2‐picolinic acid (picH). The structures fall into four general categories and are of formula: [Cr2(OMe)2(pic)4], [Cr2(hmp)2(pic)2X2] (where X = Cl, Br), [Cr2(L)2Cl4(A)2] (where L = hmp, A = H2O; L = hmp, A = pyridine; L = hmp, A = 4‐picoline; L = hep, A = H2O), and [Cr(hmp)(hmpH)Cl2. Magnetic studies show relatively weak antiferromagnetic exchange interactions between the Cr(III) centres and DFT calculations are used to develop magneto‐structural correlations, showing that the magnitude and sign of the J value is strongly dependent upon the orientation of the dihedral angle formed between the bridging Cr2O2 plane and the O–R vector of the bridging group, and the Cr–O–Cr–O dihedral angle. Chapter 3 builds on the work from the previous chapter with discussion of a large family of chromium(III) dimers, synthesised using a combination of carboxylate and diethanolamine type ligands. The compounds have the general formula [Cr2(R1‐deaH)2(O2CR2)Cl2]Cl where R1 = Me and R2 = H, Me, CMe3, Ph, 3,5‐(Cl)2Ph, (Me)5Ph, R1 = Et and R2 = H, Ph. The compound [Cr2(Me‐deaH)2Cl4] was also synthesised in order to study the effect of removing/adding the carboxylate bridge to the observed magnetic behaviour. Magnetic studies reveal ferromagnetic exchange interactions between the Cr(III) centres in the carboxylate bridged family with coupling constants in the range +0.37 < J < +8.02 cm‐1. Removal of the carboxylate to produce the dialkoxide‐bridged compound results in antiferromagnetic exchange between the Cr(III) ions. DFT calculations to further develop the magneto-structural correlations reveal the ferromagnetic exchange is the result of an orbital counter-complementarity effect occurring upon introduction of the bridging carboxylate. Chapter 4 reports a family of heterometallic Anderson‐type ‘wheels’ of general formula [MIII 2MII 5(hmp)12](ClO4)4 (where MIII = Cr or Al and MII = Ni or Zn giving [Cr2Ni5], [Cr2Zn5], [Al2Ni5] and [Al2Zn5]; hmpH = 2‐pyridinemethanol) synthesised solvothermally. The metallic skeleton describes a centred hexagon with the MIII sites disordered around the outer wheel. The structural disorder is characterised via single crystal X‐ray crystallography, 1‐3D 1H and 13C solution‐state NMR spectroscopy of the diamagnetic analogue, and solid‐state 27Al MAS NMR spectroscopy of the Al containing analogues. Alongside ESI mass spectrometry, these techniques show that structure is retained in solution, and that the disorder is present in both the solution and solid‐state. Solid‐state dc susceptibility and magnetisation measurements on [Cr2Zn5] and [Al2Ni5] reveal the Cr‐Cr and Ni‐Ni exchange interactions to be JCr‐Cr = ‐1 cm‐1 and JNi‐Ni,r = ‐5 cm‐1, JNi‐Ni,c = 10 cm‐1. Fixing these values allows us to extract JCr‐Ni,r = ‐1.2 cm‐1, JCr‐Ni,c = 2.6 cm‐1, the exchange between adjacent Ni and Cr ions on the ring is antiferromagnetic and between Cr ions on the ring and the central Ni ion is ferromagnetic. Chapter 5 focusses on planar molecules, espanding the family of heterometallic Anderson‐type ‘wheels’ discussed in chapter 4 to include MIII = Cr, Al and MII = Co, Fe, Mn, Cu, affording five new species of formulae [Cr2Co5(hmp)12](ClO4)4, [Cr2Fe5(hmp)12](ClO4)4, [Cr2Mn5(hmp)12](ClO4)4, [Cr2Cu5(hmp)12](ClO4)2(NO3)2 and [Al2Co5(hmp)12](ClO4)4. As per previous family members, the two MIII sites are disordered around the outer wheel, with the exception of [Cr2Cu5] where the the CuII sites are localised. A structurally related, but enlarged planar disc possessing a [MIII 6MII] hexagon capped on each edge by a CuII ion is also reported, which is formed only when MIII = Al and MII = Cu. In [AlIII 6CuII 7(OH)12(hmp)12](ClO4)6(NO3)2 the Anderson moiety contains a central, (symmetry‐imposed) octahedral CuII ion surrounded by a wheel of AlIII ions. Solid‐state dc susceptibility and magnetisation measurements reveal the presence of competing exchange interactions in the Anderson wheels family, and weak antiferromagnetic exchange between the CuII ions in [Al6Cu7]. Chapter 6 describes two heterometallic wheels of formula [(VIVO)2MII 5(hmp)10Cl2](ClO4)2∙2MeOH (where MII = Ni or Co) displaying the same Anderson‐type structure as seen in chapters 4 and 5, however the use of the vanadyl moiety has the effect of removing the disorder, with the two vanadyl ions sitting on opposing sides of the ring. The magnetic properties of both show competing antiferroand ferromagnetic interactions

Lake Canyon, Wasp House

Photo of an Indian ruin in Lake Canyon, a tributary of Glen Canyon, seen by Grace Fite on June 1, 196