Portfolio of compositions

The objective of my portfolio is to develop a new compositional process that involves analysing recorded sounds, interpreting and translating analyses into musical metaphors, and generating formal structures based on changes in timbre. The portfolio explores several models of compositional processes that were created in the course of my research. It analyses the strengths and weaknesses of these models, and it offers insight into the ways that the compositional process may be further developed

Portfolio of compositions

The objective of my portfolio is to develop a new compositional process that involves analysing recorded sounds, interpreting and translating analyses into musical metaphors, and generating formal structures based on changes in timbre. The portfolio explores several models of compositional processes that were created in the course of my research. It analyses the strengths and weaknesses of these models, and it offers insight into the ways that the compositional process may be further developed

Good Intentions Gone Awry—A Proposal for Fundamental Change in Criminal Sentencing

This article will discuss the individual treatment model and analyze the fallacies of current sentencing practices and philosophies. Concluding that the treatment model is inappropriate because it fails to consider fundamental principles of justice and the purposes of the criminal law, it will offer an alternative proposal for sentencing that is not dependent on the theory of rehabilitation

Robust machine learning algorithm to search for continuous gravitational waves

Many continuous gravitational wave searches are affected by instrumental spectral lines that could be confused with a continuous astrophysical signal. Several techniques have been developed to limit the effect of these lines by penalizing signals that appear in only a single detector. We have developed a general method, using a convolutional neural network, to reduce the impact of instrumental artifacts on searches that use the SOAP algorithm Bayley et al. [Phys. Rev. D 100, 023006 (2019)]. The method can identify features in corresponding frequency bands of each detector and classify these bands as containing a signal, an instrumental line, or noise. We tested the method against four different datasets: Gaussian noise with time gaps, data from the final run of Initial LIGO (S6) with signals added, the reference S6 mock data challenge dataset Walsh et al. [Phys. Rev. D 94, 124010 (2016)] and signals injected into data from the second advanced LIGO observing run (O2). Using the S6 mock data challenge dataset and at a 1% false alarm probability we showed that at 95% efficiency a fully automated SOAP search has a sensitivity corresponding to a coherent signal-to-noise ratio of 110, equivalent to a sensitivity depth of 10  Hz−1/2, making this automated search competitive with other searches requiring significantly more computing resources and human intervention

Dual-specificity phosphatase 5 controls the localized inhibition, propagation, and transforming potential of ERK signaling

Deregulated extracellular signal-regulated kinase (ERK) signaling drives cancer growth. Normally, ERK activity is self-limiting by the rapid inactivation of upstream kinases and delayed induction of dual-specificity MAP kinase phosphatases (MKPs/DUSPs). However, interactions between these feedback mechanisms are unclear. Here we show that, although the MKP DUSP5 both inactivates and anchors ERK in the nucleus, it paradoxically increases and prolongs cytoplasmic ERK activity. The latter effect is caused, at least in part, by the relief of ERK-mediated RAF inhibition. The importance of this spatiotemporal interaction between these distinct feedback mechanisms is illustrated by the fact that expression of oncogenic BRAF(V600E), a feedback-insensitive mutant RAF kinase, reprograms DUSP5 into a cell-wide ERK inhibitor that facilitates cell proliferation and transformation. In contrast, DUSP5 deletion causes BRAF(V600E)-induced ERK hyperactivation and cellular senescence. Thus, feedback interactions within the ERK pathway can regulate cell proliferation and transformation, and suggest oncogene-specific roles for DUSP5 in controlling ERK signaling and cell fate

Spinal Metastases and the Evolving Role of Molecular Targeted Therapy, Chemotherapy, and Immunotherapy

Metastatic involvement of the spine is a common complication of systemic cancer progression. Surgery and external beam radiotherapy are palliative treatment modalities aiming to preserve neurological function, control pain and maintain functional status. More recently, with development of image guidance and stereotactic delivery of high doses of conformal radiation, local tumor control has improved; however recurrent or radiation refractory disease remains a significant clinical problem with limited treatment options. This manuscript represents a narrative overview of novel targeted molecular therapies, chemotherapies, and immunotherapy treatments for patients with breast, lung, melanoma, renal cell, prostate, and thyroid cancers, which resulted in improved responses compared to standard chemotherapy. We present clinical examples of excellent responses in spinal metastatic disease which have not been specifically documented in the literature, as most clinical trials evaluate treatment response based on visceral disease. This review is useful for the spine surgeons treating patients with metastatic disease as knowledge of these responses could help with timing and planning of surgical interventions, as well as promote multidisciplinary discussions, allowing development of an individualized treatment strategy to patients presenting with widespread multifocal progressive disease, where surgery could lead to suboptimal results

Structural and functional characterization of IdiA/FutA (Tery_3377), an iron-binding protein from the ocean diazotroph Trichodesmium erythraeum

Atmospheric nitrogen fixation by photosynthetic cyanobacteria (diazotrophs) strongly influences oceanic primary production and in turn affects global biogeochemical cycles. Species of the genus Trichodesmium are major contributors to marine diazotrophy, accounting for a significant proportion of the fixed nitrogen in tropical and subtropical oceans. However, Trichodesmium spp. are metabolically constrained by the availability of iron, an essential element for both the photosynthetic apparatus and the nitrogenase enzyme. Survival strategies in low-iron environments are typically poorly characterized at the molecular level, because these bacteria are recalcitrant to genetic manipulation. Here, we studied a homolog of the iron deficiency-induced A (IdiA)/ferric uptake transporter A (FutA) protein, Tery_3377, which has been used as an in situ iron-stress biomarker. IdiA/FutA has an ambiguous function in cyanobacteria, with its homologs hypothesized to be involved in distinct processes depending on their cellular localization. Using signal sequence fusions to GFP and heterologous expression in the model cyanobacterium Synechocystis sp. PCC 6803, we show that Tery_3377 is targeted to the periplasm by the twin-arginine translocase and can complement the deletion of the native Synechocystis ferric-iron ABC transporter periplasmic binding protein (FutA2). EPR spectroscopy revealed that purified recombinant Tery_3377 has specificity for iron in the Fe3+ state, and an X-ray crystallography–determined structure uncovered a functional iron substrate–binding domain, with Fe3+ pentacoordinated by protein and buffer ligands. Our results support assignment of Tery_3377 as a functional FutA subunit of an Fe3+ ABC transporter but do not rule out dual IdiA function