Vindicating Vague Objects

Until recently, vagueness has been seen as a product of representation alone; a byproduct of the limitations of our language or our ability to know the truth. To endorse the contrasting idea that vagueness can come from the world – and to endorse the existence of vague objects – has often been a maligned enterprise. Indeed, proponents of the view have been charged with mistaking features of the world for features of our language or minds, mistaking a question of language and epistemology for a question of metaphysics. Further, even granting the plausibility of such a view, the thesis that vague objects can exist has been laden with commitment to problematic notions such as vague identity and vague existence. This thesis examines the prospects of defending the idea that vague objects exist, vindicating the cogency of such a view and decoupling it from these problematic notions. Chapter 1 begins by examining Gareth Evans’ seminal reductio against vague objects, in which the existence of vague objects is tied to the fate of vague identity. Engaging with the literature that Evans’ paper generated, we show that vague objects need not be committed to a contradictory notion of vague identity; rather, one can defend an account of vague objects without the need for revisionary logics or gerrymandered notions of identity. Chapter 2 extends the investigation of vague objects by considering the Problem of the Many, a powerful paradox which appears to undermine seemingly well-founded mereological principles and intuitions. After evaluating existing solutions to the problem, we show how vague objects can be used to develop a novel solution that is couched within the logical apparatus defended in Chapter 1. We then demonstrate how the novel solution offers a fruitful means of responding to the problem while retaining desired mereological principles. Chapter 3 draws on the discussion in the preceding chapters to defend the cogency of vague objects in the context of contemporary views of metaphysical vagueness. Specifically, we show that defending the existence of vague objects has genuine utility for supporting a defence of the intelligibility of metaphysical vagueness. We end with a brief examination of the prospects of extending the novel account of vague objects developed, and consider how this view may be applied to future investigations in metaphysics.Thesis (MPhil) -- University of Adelaide, School of Humanities, 201

A programmable, multi-format photonic transceiver platform enabling flexible optical networks

Development of programmable photonic devices for future flexible optical networks is ongoing. To this end, an innovative, multi-format QAM transmitter design is presented. It comprises a segmented-electrode InP IQ-MZM to be fabricated in InP, which can be directly driven by low-power CMOS logic. Arbitrary optical QAM format generation is made possible using only binary electrical signals, without the need for high-performance DACs and high-swing linear drivers. The concept enables a host of Tx-side DSP functionality, including the spectral shaping needed for Nyquist-WDM system concepts. In addition, we report on the development of an optical channel MUX/DEMUX, based on arrays of microresonator filters with reconfigurable bandwidths and center wavelengths. The device is intended for operation with multi-format flexible transceivers, enabling Dense (D)WDM superchannel aggregation and arbitrary spectral slicing in the context of a flexible grid environment

Restless legs syndrome is contributing to fatigue and low quality of life levels in hemodialysis patients

AIM: To examine whether hemodialysis (HD) patients with restless legs syndrome (RLS) are subjects of greater fatigue and impaired quality of life (QoL) compared to HD patients without RLS. METHODS: Eighty five stable HD patients participated in this study. According to their RLS status, the patients were divided into the RLS group (n = 23) and the non-RLS group (n = 62). QoL, fatigue, sleep quality, daily sleepiness and depression symptoms were assessed by using various questionnaires. Finally, biochemical parameters including iron, ferritin, hemoglobin, hematocrit and parathormone were assessed. RESULTS: The HD patients with RLS scored worse in all the questionnaires used in the study (P < 0.05). The patients with RLS were more likely to receive the HD therapy on the morning shift, whilst 43.5% of the RLS patients reported to experience the RLS symptoms also during HD. The severity of RLS was correlated with fatigue, depression score and sleep quality (P < 0.05). CONCLUSION: HD patients with RLS are subject to lower QoL related parameters and greater fatigue compared to HD patients without RLS. RLS should be successfully managed in order to improve the QoL of the sufferers

The ecology of immune state in a wild mammal, Mus musculus domesticus

The immune state of wild animals is largely unknown. Knowing this and what affects it is important in understanding how infection and disease affects wild animals. The immune state of wild animals is also important in understanding the biology of their pathogens, which is directly relevant to explaining pathogen spillover among species, including to humans. The paucity of knowledge about wild animals' immune state is in stark contrast to our exquisitely detailed understanding of the immunobiology of laboratory animals. Making an immune response is costly, and many factors (such as age, sex, infection status, and body condition) have individually been shown to constrain or promote immune responses. But, whether or not these factors affect immune responses and immune state in wild animals, their relative importance, and how they interact (or do not) are unknown. Here, we have investigated the immune ecology of wild house mice—the same species as the laboratory mouse—as an example of a wild mammal, characterising their adaptive humoral, adaptive cellular, and innate immune state. Firstly, we show how immune variation is structured among mouse populations, finding that there can be extensive immune discordance among neighbouring populations. Secondly, we identify the principal factors that underlie the immunological differences among mice, showing that body condition promotes and age constrains individuals’ immune state, while factors such as microparasite infection and season are comparatively unimportant. By applying a multifactorial analysis to an immune system-wide analysis, our results bring a new and unified understanding of the immunobiology of a wild mammal

Comparing serial X-ray crystallography and microcrystal electron diffraction (MicroED) as methods for routine structure determination from small macromolecular crystals.

Innovative new crystallographic methods are facilitating structural studies from ever smaller crystals of biological macromolecules. In particular, serial X-ray crystallography and microcrystal electron diffraction (MicroED) have emerged as useful methods for obtaining structural information from crystals on the nanometre to micrometre scale. Despite the utility of these methods, their implementation can often be difficult, as they present many challenges that are not encountered in traditional macromolecular crystallography experiments. Here, XFEL serial crystallography experiments and MicroED experiments using batch-grown microcrystals of the enzyme cyclophilin A are described. The results provide a roadmap for researchers hoping to design macromolecular microcrystallography experiments, and they highlight the strengths and weaknesses of the two methods. Specifically, we focus on how the different physical conditions imposed by the sample-preparation and delivery methods required for each type of experiment affect the crystal structure of the enzyme

Identification of PSD-95 in the Postsynaptic Density Using MiniSOG and EM Tomography

Combining tomography with electron microscopy (EM) produces images at definition sufficient to visualize individual protein molecules or molecular complexes in intact neurons. When freeze-substituted hippocampal cultures in plastic sections are imaged by EM tomography, detailed structures emerging from 3D reconstructions reveal putative glutamate receptors and membrane-associated filaments containing scaffolding proteins such as postsynaptic density (PSD)-95 family proteins based on their size, shape, and known distributions. In limited instances, structures can be identified with enhanced immuno-Nanogold labeling after light fixation and subsequent freeze-substitution. Molecular identification of structure can be corroborated in their absence after acute protein knockdown or gene knockout. However, additional labeling methods linking EM level structure to molecules in tomograms are needed. A recent development for labeling structures for TEM employs expression of endogenous proteins carrying a green fluorescent tag, miniSOG, to photoconvert diaminobenzidine (DAB) into osmiophilic polymers. This approach requires initial mild chemical fixation but many of structural features in neurons can still be discerned in EM tomograms. The photoreaction product, which appears as electron-dense, fine precipitates decorating protein structures in neurons, may diffuse to fill cytoplasm of spines, thus obscuring specific localization of proteins tagged with miniSOG. Here we develop an approach to minimize molecular diffusion of the DAB photoreaction product in neurons, which allows miniSOG tagged molecule/complexes to be identified in tomograms. The examples reveal electron-dense clusters of reaction product labeling membrane-associated vertical filaments, corresponding to the site of miniSOG fused at the C-terminal end of PSD-95-miniSOG, allowing identification of PSD-95 vertical filaments at the PSD. This approach, which results in considerable improvement in the precision of labeling PSD-95 in tomograms without complications due to the presence of antibody complexes in immunogold labeling, may be applicable for identifying other synaptic proteins in intact neurons

Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL

Differential localization to the inner and outer mitochondrial membranes regulates PINK1 stability and function

Trade and trade-offs: shipping in changing climates

This paper addresses the evolution of maritime transport demand in response to global climate change mitigation and adaptation efforts. The complexity of the global shipping system makes predicting volumes and patterns of long-term future international maritime trade a challenging task which is best explored by building scenarios rather than ‘precise’ forecasts. We present four contrasting scenarios of international maritime trade out to 2050, available in high resolution in terms of the dimensions studied (regions, countries, commodities, decades), which are consistent with high and low levels of global CO2 mitigation and associated climate impacts. The scenarios project trade increasing to between two and four times the 2010 value by 2050. Scenarios characterised by low temperature increases and material intensity lead to the lower bound trade increase with high trade growth in bioenergy commodities. Unfettered production growth across countries, high temperature increases and material intensity lead to a quadrupling of trade across energy, containerised, dry and wet commodities. The estimated range is lower than those in existing scenarios and forecasts in which globalisation is assumed to continue apace. The scenarios which project the highest growth presupposes both limited decarbonisation (in contrast to the Paris Agreement) and continued growth in expanding markets. The scenarios therefore become a valuable policy and decision-making tool to address technological and operational change required of the shipping sector, if it is to deliver mitigation in line with the Paris Agreement

The p.M292T NDUFS2 mutation causes complex I-deficient Leigh syndrome in multiple families

Isolated complex I deficiency is the most frequently observed oxidative phosphorylation defect in children with mitochondrial disease, leading to a diverse range of clinical presentations, including Leigh syndrome. For most patients the genetic cause of the biochemical defect remains unknown due to incomplete understanding of the complex I assembly process. Nonetheless, a plethora of pathogenic mutations have been described to date in the seven mitochondrial-encoded subunits of complex I as well as in 12 of the nuclear-encoded subunits and in six assembly factors. Whilst several mitochondrial DNA mutations are recurrent, the majority of these mutations are reported in single families. We have sequenced core structural and functional nuclear-encoded subunits of complex I in a cohort of 34 paediatric patients with isolated complex I deficiency, identifying pathogenic mutations in 6 patients. These included a novel homozygous NDUFS1 mutation in an Asian child with Leigh syndrome, a previously identified NDUFS8 mutation (c.236C>T, p.P79L) in a second Asian child with Leigh-like syndrome and six novel, compound heterozygous NDUFS2 mutations in four white Caucasian patients with Leigh or Leigh-like syndrome. Three of these children harboured an identical NDUFS2 mutation (c.875T>C, p.M292T), which was also identified in conjunction with a novel NDUFS2 splice site mutation (c.866+4A>G) in a fourth Caucasian child who presented to a different diagnostic centre, with microsatellite and single nucleotide polymorphism analyses indicating that this was due to an ancient common founder event. Our results confirm that NDUFS2 is a mutational hotspot in Caucasian children with isolated complex I deficiency and recommend the routine diagnostic investigation of this gene in patients with Leigh or Leigh-like phenotypes

The Contribution of Uterine Artery Embolization as a Safe Treatment Option for Uterine Fibroids

Uterine fibroids have remarkably heterogeneous clinical characteristics with unknown exact etiology. The treatment of fibroids should be individualized based on their size, location, growth rate, the symptoms that they cause, the desire to have children and the age of the woman. Embolization is currently the most advanced non-surgical technique. The majority of women report satisfactory post-treatment results like shorter hospitalization period and recovery time in comparison to hysterectomy and improvement or complete remission of clinical symptoms. Complications include amenorrhea (in the majority of cases: recurrence after three months) and infections that are generally treated with antibiotics. The results from most clinical studies and our published experience indicate that embolization improves pelvic symptoms related to uterine fibroids. Collaborative efforts between gynecologists and interventional radiologists are necessary in order to optimize the safety and efficacy of this procedure. In the future, embolization could be generally recommended as treatment option for women who desire future fertility/pregnancy