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We construct a thin‐sheet dynamical model of the New Zealand plate boundary that includes faults. Our model fits fault slip rates, style of distributed deformation, and is constrained by relative plate boundary motion. We assume a pseudo‐plastic rheology and achieve a best fit to slip rate observations with a deviatoric stress magnitude of 20 MPa. Modeled local forces are significant at Puysegur and Hikurangi subduction zones, and smaller forces are related to mantle downwelling beneath South Island and Havre Trough mantle upwelling. Modeled tractions on faults are mostly 5–20 MPa, similar to or slightly smaller than stress magnitudes adjacent to faults. Modeled shear tractions are generally 2–10 MPa, comparable to stress drops during earthquakes. Modeled stress orientations and fault dips suggest that many faults are not optimally oriented for their style of faulting. Notably small traction magnitudes of <5 MPa and shear tractions of <0.5 MPa are modeled for faults in the central North Island Dextral Fault Belt (NIDFB), which we infer to be very poorly oriented. Friction coefficients on faults (ratio of shear stress to effective normal stress) are in the range 0.1–0.3 for major crustal faults such as the Alpine Fault and Marlborough faults, but subduction zones and the NIDFB have values <0.1. We propose that low values of long‐term fault strength, shear stress resolved onto the fault, and overall magnitudes of deviatoric stress in the crust are a consequence of dynamic weakening of faults during fault slip. Plain Language Summary: Earthquakes occur when there is movement along faults. However, the strength of friction resisting movement on faults is debated. We construct a model of major faults through New Zealand that fits observed long‐term fault movement rates. We estimate forces driving movement on faults along with the physical properties of those major faults and of the crust between major faults. We find that many faults are not optimally oriented to move in the direction they are observed to move given the modeled forces acting on them. We estimate low levels of friction on faults, indicating that relatively small forces (averaged over thousands of years) are required to cause movement on faults. Key Points: Crustal deviatoric stress magnitudes are ∼20 MPa and fault tractions are 5–20 MPaShear tractions on faults are 0.5–10 MPa, comparable to earthquake stress dropsFriction coefficients are 0.05–0.3 for most crustal faults and are <0.1 for most subduction‐related faults [ABSTRACT FROM AUTHOR]

The effects of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) and gamma radiation, and PDT and hyperthermia (HT) are investigated in human glioma spheroids. In the case of ionizing radiation and PDT, the degree of interaction between the two modalities depends in a complex manner on a number of factors, including light fluence, fluence rate and radiation dose. It is shown that, under certain conditions, PDT and gamma radiation interact synergistically to produce enhanced cell kill. The degree of interaction appears to be independent of both sequence and time intervals investigated. TUNEL assays show that low fluence-rate ALA-PDT is a very efficient inducer of apoptosis, whereas neither high-fluence rate PDT nor ionizing radiation results in significant apoptosis in this system. Synergistic interactions between HT and PDT are observed when the two modalities are given concurrently. The degree of synergism increases with increasing temperature and light fluence. It is shown that apoptosis is the primary mode of cell death following combined HT and low-fluence rate ALA-PDT.

An in vivo model has been developed for the study of photodynamic therapy (PDT) and anti-angiogenic treatments. Significant damage to the vasculature of the chick chorioallantoic membrane (CAM) was observed immediately following PDT with 5-aminolevulinic acid (ALA). Multicell human glioma spheroids were placed on the CAM at day five of embryonic development, however, neovascularization was not observed.

Although 5-aminolevulinic acid (ALA) has several advantages over other photosensitizers, its hydrophilic nature gives rise to relatively poor transport across cell membranes. Esterification of ALA is a commonly used strategy to improve the effectiveness of ALA. In this study, the effectiveness of photodynamic therapy (PDT) in human glioma spheroids incubated in ALA, or ALA esters, is investigated. Spheroid survival and growth are monitored following PDT at representative drug concentrations and light fluences. It is shown that the response of human glioma spheroids to PDT with lipophilic ester derivatives, such as benzyl-ALA and hexyl-ALA, is equivalent to that observed with ALA, however, this equivalency is observed for ester concentrations 10 to 20 times lower than the parent compound.

The response of human glioma spheroids to 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) is investigated. A two-photon fluorescence microscopy technique is used to show that human glioma cells readily convert ALA to protoporphyrin IX throughout the entire spheroid volume. The central finding of this study is that the response of human glioma spheroids to ALA-mediated PDT depends not only on the total fluence, but also on the rate at which the fluence is delivered. At low fluences (< or = 50 J cm-2), lower fluence rates are more effective. At a fluence of 50 J cm-2, near-total spheroid kill is observed at fluence rates of as low as 10 mW cm-2. The fluence rate effect is not as pronounced at higher fluences (> 50 J cm-2), where a favorable response is observed throughout the range of fluence rates investigated. The clinical implications of these findings are discussed.

We assess the stress field that drives lithospheric deformation, focusing on the active New Zealand plate-boundary zone between the Australian and Pacific plates. Here there is a rich database for the horizontal velocity field, and also crustal structure used to derive gravitational potential energy (GPE). We solve the stress balance equations, in the context of a thin sheet model of a viscously deforming lithosphere, for characteristic deviatoric stresses and viscosities, defined as the integral of these with depth (divided by the layer thickness), using the stress method of Flesch et al. where the input parameters are the fields of strain rate and GPE that apply to the sheet. Synthetic tests show that the stress method is able to resolve the stress field even with high (20 per cent) levels of noise in the input strain rates, and the mean stress is a very robust feature of the inversions, regardless of noise levels. We invert for the stress and viscosity fields in New Zealand, calculating the field of GPE from topography/bathymetry and crustal data, and the field of strain rates from either a long-term (multimillennial) velocity field inferred from the rate and pattern of Quaternary faulting or a short-term (decadal) velocity field directly observed with Global Positioning System (GPS) measurements. In addition, we consider the effect of shear stresses on the subducted plate interface along the Hikurangi Margin (5–15 MPa), or regionally. We explore the effect of GPE on the inversion results by calculating these for a range of deforming layers (i.e. thin sheet with 35–150 km thickness), in effect sampling the lithospheric strength in the crust and mantle. The results show that the derived stress magnitudes (square root second invariant of the stress deviator) are in the range 0–35 MPa, with mean values of 13 ± 1 MPa for all models, comparable to typical earthquake stress drops. Gravitationally induced stresses account for approximately half of the full deviatoric stress. Effective characteristic viscosities are 0.5–5 × 1021 Pa s in the deforming zone, with an approximate inverse relation between strain rate and viscosity, most likely controlled by thermal structure and/or lithology. [ABSTRACT FROM AUTHOR]