Sidewall control of static azimuthal bistable nematic alignment states

Stable azimuthal alignment states have been created in the plane of a homogeneous layer of nematic liquid crystal by the action of one or more sawtooth sidewalls. The alignment states in devices with two sawtooth sidewall structures, either in-phase or in anti-phase, and with one sawtooth wall opposite a flat wall have been investigated as a function of the sawtooth pitch. The optical textures of the observed states are in excellent agreement with the predictions of nematic Q-tensor theory. The frequencies of occurrence of the different states are broadly consistent with the expected inverse correlation with the Q-tensor predictions for their energy

Flexoelectric polarisation effects in nematic liquid crystal phase gratings

Nematic phase gratings have been studied in which a planar nematic layer of thickness 17.2 μm is sandwiched between two glass substrates coated with an alignment polymer. The upper substrate is a continuous earth plane and the lower substrate has a patterned electrode of interdigitated stripes (electrodes and gaps are both 40 μm wide). Reorientation of the nematic liquid crystal occurs in response to d.c. electric fields applied between the interdigitated electrodes. These nematic reorientation regions have been used to investigate the influence of the flexoelectric polarisation in the nematic liquid crystal by observing the resultant (i) movement of tilt fringes in a Mach-Zehnder interferometer, and (ii) optical diffraction patterns. In the Mach-Zehnder interferometer the periodic variation of the refractive index resulting from the periodic distortion profile is measured directly from the displacement of the tilt fringes. The asymmetry in the response to positive and negative polarities of the d.c. voltage for both measurement techniques is directly related to the sum of the flexoelectric coefficients, e1 + e3

Biodiversity of nematode assemblages from the region of the Clarion-Clipperton Fracture Zone, an area of commercial mining interest

BACKGROUND: The possibility for commercial mining of deep-sea manganese nodules is currently under exploration in the abyssal Clarion-Clipperton Fracture Zone. Nematodes have potential for biomonitoring of the impact of commercial activity but the natural biodiversity is unknown. We investigate the feasibility of nematodes as biomonitoring organisms and give information about their natural biodiversity. RESULTS: The taxonomic composition (at family to genus level) of the nematode fauna in the abyssal Pacific is similar, but not identical to, the North Atlantic. Given the immature state of marine nematode taxonomy, it is not possible to comment on the commonality or otherwise of species between oceans. The between basin differences do not appear to be directly linked to current ecological factors. The abyssal Pacific region (including the Fracture Zone) could be divided into two biodiversity subregions that conform to variations in the linked factors of flux to the benthos and of sedimentary characteristics. Richer biodiversity is associated with areas of known phytodetritus input and higher organic-carbon flux. Despite high reported sample diversity, estimated regional diversity is less than 400 species. CONCLUSION: The estimated regional diversity of the CCFZ is a tractable figure for biomonitoring of commercial activities in this region using marine nematodes, despite the immature taxonomy (i.e. most marine species have not been described) of the group. However, nematode ecology is in dire need of further study

Role of tumour necrosis factor gene polymorphisms (-308 and -238) in breast cancer susceptibility and severity

Introduction Genetic polymorphisms in the promoter region of the tumour necrosis factor (TNF) gene can regulate gene expression and have been associated with inflammatory and malignant conditions. We have investigated two polymorphisms in the promoter of the TNF gene (-308 G>A and -238 G>A) for their role in breast cancer susceptibility and severity by means of an allelic association study. Methods Using a case–control study design, breast cancer patients (n = 709) and appropriate age-matched and sex-matched controls obtained from the Breast Screening Unit (n = 498) were genotyped for these TNF polymorphisms, using a high-throughput allelic discrimination method. Results Allele frequencies for both polymorphisms were similar in both breast cancer cases and controls. However, the -308 polymorphism was found to be associated with vascular invasion in breast tumours (P = 0.024). Comparison with other standard prognostic indices did not show any association for either genotype. Conclusions We demonstrated no association between the -308G>A polymorphism and the -238G>A polymorphism in the promoter region of TNF and susceptibility to breast cancer, in a large North European population. However, the -308 G>A polymorphism was found to be associated with the presence of vascular invasion in breast tumours

The influence of hypoxia and pH on aminolaevulinic acid-induced photodynamic therapy in bladder cancer cells in vitro

Photodynamic therapy (PDT) is a cancer treatment based on the interaction of light and a photosensitizing chemical. The photosensitizer protoporphyrin IX (PpIX) is generated via the haem biosynthetic pathway after administration of aminolaevulinic acid (ALA). The cellular microenvironment of tumours is hypoxic and acidotic relative to normal tissue, which may influence PpIX generation and compromise PDT efficacy. This study used bladder cancer cells, incubated with ALA at various oxygen tensions and H+ ion concentrations, and assessed the effects on PpIX generation and PDT sensitivity. PpIX production was reduced at 0%, 2.5% (19 mmHg) and 5% (38 mmHg) oxygen compared with that at 21% (160 mmHg) oxygen (0.15, 0.28 and 0.398 ng microg(-1) protein compared with 0.68 ng microg(-1) respectively; P < 0.05). The response to PDT was abolished by hypoxia, as a result of both reduced PpIX synthesis and reduced PDT toxicity. PpIX production was greater at pH 7.0 and 6.5 (0.75 and 0.66 ng microg(-1)) compared with that at pH 7.4 and 5.5 (0.41 and 0.55 ng microg(-1) respectively). PDT cytotoxicity was enhanced at lower pH values. These results suggest that ALA-induced PDT may be inhibited by hypoxia due to reduced intrinsic PpIX synthesis. Acidosis may slightly enhance the efficacy of ALA-induced PDT

Australian quasigeoid modelling: Review, current status and future plans

We provide a historical review and critique of regional geoid and quasigeoid modelling over the Australian continent, covering the earliest models from the late 1960s through to the present day and beyond. The most recently released official model for GPS/GNSS surveyors, AUSGeoid2020, was specifically calculated to enable them to determine Australian Height Datum heights from Geocentric Datum of Australia 2020 ellipsoidal heights in a more direct manner without the need for post-surveying adjustments. We summarise the deficiencies in the Australian Height Datum and how they are now being addressed by a proposed new vertical height system that is underpinned by a gravimetric-only quasigeoid model. We also summarise the results of some experiments that we have conducted to explore potential refinements that could be made to our computational processes, and future plans to acquire gravity data in the problematic coastal zones using airborne methods

Characterisation of the centrosome protein Cep63

In dividing cells, centrosomes act as the primary microtubule organising centre to orchestrate mitotic spindle assembly. Bipolar spindle assembly is responsible for accurate segregation of sister chromatids, such that each daughter cell receives an identical copy of the genome. Changes in centrosome number can lead to a lack of mitotic fidelity and genome instability. Chromosomes are replicated in a controlled and timely fashion and the same is true for centrosomes so that cells enter mitosis with two centrosomes. Further to their role in spindle assembly, centrosomes are also important in cell cycle regulation and DNA damage checkpoint signalling. Centrosomes are particularly important in the regulation of neuroepithelial cell division in the developing brain: all known incidences of primary microcephaly are caused by mutations in centrosome or spindle pole proteins. Xenopus laevis Cep63 is a target of DNA damage kinase, ATM, and it’s important for the formation of bipolar mitotic spindles (Smith et al., 2009). Therefore, Cep63 is an exciting candidate for maintenance of genome stability. Human Cep63 has been identified as a centrosome protein (Andersen et al., 2003), but its function was uncharacterised. In this thesis Cep63 was shown to be a constitutive centrosome protein, which plays a role in the regulation of centriole duplication. Cep152 was identified as a Cep63 interacting protein; and Cep63 and Cep152 are dependent on each other for their centrosomal localisation. Cep152 is required for centriole duplication via recruitment of essential duplication factors, Plk4 and CPAP, to the centrosome (Dzhindzhev et al., 2010b, Cizmecioglu et al., 2010, Hatch et al., 2010b). Furthermore, mouse embryonic fibroblasts in which the Cep63 gene is disrupted show decreased centriole numbers and signs of genome instability. Intriguingly, preliminary analysis of mouse embryos points to a potential link between Cep63 deficiency and microcephaly. We propose that Cep63 and Cep152 function together to ensure correct centrosomal levels of the essential centriole duplication factors Plk4 and CPAP

Transforming growth factor-beta and endoglin signaling orchestrate wound healing

Physiological wound healing is a complex process requiring the temporal and spatial co-ordination of various signaling networks, biomechanical forces, and biochemical signaling pathways in both hypoxic and non-hypoxic conditions. Although a plethora of factors are required for successful physiological tissue repair, transforming growth factor beta (TGF-β) expression has been demonstrated throughout wound healing and shown to regulate many processes involved in tissue repair, including production of ECM, proteases, protease inhibitors, migration, chemotaxis, and proliferation of macrophages, fibroblasts of the granulation tissue, epithelial and capillary endothelial cells. TGF-β mediates these effects by stimulating signaling pathways through a receptor complex which contains Endoglin. Endoglin is expressed in a broad spectrum of proliferating and stem cells with elevated expression during hypoxia, and regulates important cellular functions such as proliferation and adhesion via Smad signaling. This review focuses on how the TGF-β family and Endoglin, regulate stem cell availability, and modulate cellular behavior within the wound microenvironment, includes current knowledge of the signaling pathways involved, and explores how this information may be applicable to inflammatory and/or angiogenic diseases such as fibrosis, rheumatoid arthritis and metastatic cancer

Factors affecting amninolaevulinic acid-induced generation of protoporphyrin IX

Photodynamic therapy (PDT) may cause tumour cell destruction by direct toxicity or by inducing cellular hypoxia as a result of microcirculatory shutdown. Aminolaevulinic acid (ALA) causes cellular accumulation of protoporphyrin IX (PPIX) in cells exposed to it in excess. PPIX can be used as a photosensitizer for PDT. Microcirculatory shutdown may be induced by toxicity to the endothelial and vascular smooth muscle (VSM) cells or by release of vasoactive substances. We have studied whether PPIX is produced by endothelial, VSM and tumour cells on exposure to ALA and whether these cell lines are directly damaged by PDT in vitro. Tumour endothelial cells are angiogenic and we have, therefore, investigated the effect of cellular proliferation rates on PPIX generation. Tumour cells generate more PPIX intracellularly than the non-neoplastic cell lines studied and are correspondingly more sensitive to PDT-induced cytotoxicity. Endothelial cells are sensitive to PDT-induced cytotoxicity and accumulate between 1.5 and four times more PPIX when proliferating (as during tumour-induced angiogenesis) than when quiescent. We conclude that PPIX-mediated PDT may exert some of its effects on the microcirculation of treated tissues by direct toxicity to endothelial and VSM cells, and that this toxicity may be enhanced in the tumour microenvironment