Pivotal Transformations: The Changing Voice in Anne Sexton\u27s Poetry

Critics such as Ralph Mills, Suzanne Juhasz, and Jane McCabe have generally focused on the confessional or feminist aspects of Anne Sexton\u27s poetry, most especially in To Bedlam and Part Way Back (1960), All My Pretty Ones (1962), Live or Die (1966), and Love Poems (1969). Those who have examined Transformations (1971)-and its fairy-tale world-have also paid particular attention either to its feminist approach or its confessional connections. These critics suggest that Sexton exists in her poetry as a confessional poet striving to move beyond parental restrictions and childhood experiences or they reveal Sexton as either Madonna or Witch. These and other critics, however, fail to discern that Sexton existed as both a confessional and a feminist poet throughout her career because she did not abandon either poetic root; she merely displayed a change in her poetic voice. Consequently, Transformations exists as a pivotal marker between the dissatisfied life that fed her 1960s confessional career and her post-transformation, angry and God-seeking stage wherein she attempted to take control and to accept life as mortal and imperfect. The poetry within Transformations pinpoints the shift of her poetic voice where Sexton no longer exists as a young victim of outside forces but as a sage witch-woman advising the upcoming generations. This experienced voice absorbs life\u27s wisdom and final1y understands it. Thereby she attempts to transfer this knowledge to the naive and youthful through her protective, cautionary voice manifested in the collection of seemingly unthreatening fairy tales. In this study Sexton\u27s voice is divided into three major stages. Chapter One details the emergence of her poetic voice in both To Bedlam and Part Way Back and All My Pretty Ones. Here, this voice is dependent because it remains other-defined, vacillating between madness and loss. Similarly, Chapter Two describes Sexton as having made some steps in her poetic development, but again she fluctuates, this time between melancholy and passion, her voice and work remaining parochial and stunted. Both chapters analyze how Sexton\u27s voice reflects her themes as well as gender and societal roles. Chapter Three, conversely, not only examines the expansion of Sexton\u27s voice in Transforniations and its influence on themes, gender and societal roles but also explains the pivotal role it played in Sexton\u27s poetic development. In Sexton\u27s first four collections she utilizes a voice determined by biographical and social circumstances and incapable of self-definition; here in the fifth collection, however, she does not exist as powerless and malleable but as authoritative and steadfast. Transformations, moreover, anticipates and predetermines the new characteristics of her subsequent collections. Chapter Four discusses The Book of Folly (1972), The Death Notebooks (1974), and The Awful Rowing Toward God (1975), volumes which inevitably provide an unapologetic, accusatory voice, criticizing her therapist, her father, and her self-all this while Sexton finds herself again alone, once more courting and, finally, embracing death. This concluding section reveals a post-transformational voice with its themes and roles. The Epilogue specifies areas to be critically explored in order to understand more fully the development of Sexton\u27s poetic voice

The Effect of Iron Dextran Injection on Daily Weight Gain and Haemoglobin Values in Whole Milk Fed Calves

Anaemia caused by iron deficiency has long been reported in dairy calves. This study investigated iron deficiency anaemia on UK dairy farms feeding whole milk and evaluated the effect of iron supplementation on the daily weight gain (DG) and haemoglobin (Hb) levels of these calves. Two-hundred-and-thirty-seven calves were enrolled across six farms. At enrolment, calves were randomly allocated to either receive treatment with iron injection (INJ; n = 120) consisting of 5 mL (1 g iron) of iron dextran (Uniferon 20% Injection, Pharmacosmos) or no injection, control (CON; n = 117). Calves were blood-sampled for Hb and total proteins and weighed at weeks one, six and 12 of age. Iron had a significant effect on DG from one to six weeks, with an average 78 g/d (SD 18 g/d, n = 188, 95% Confidence interval: 44–112 g/d, p < 0.001) DG increase in the INJ calves. Iron had a significant effect on Hb concentration at six weeks between the INJ group and CON group (110.7 (SD 12.4) versus 94.9 g/L (SD 13.2), respectively). Calves with a higher growth rate from one to six weeks were more likely to have low Hb levels at six weeks. There was farm variation in both Hb levels and DG, however, despite this, there was an effect of iron across all farms

Geometric Algebra Model of Distributed Representations

Formalism based on GA is an alternative to distributed representation models developed so far --- Smolensky's tensor product, Holographic Reduced Representations (HRR) and Binary Spatter Code (BSC). Convolutions are replaced by geometric products, interpretable in terms of geometry which seems to be the most natural language for visualization of higher concepts. This paper recalls the main ideas behind the GA model and investigates recognition test results using both inner product and a clipped version of matrix representation. The influence of accidental blade equality on recognition is also studied. Finally, the efficiency of the GA model is compared to that of previously developed models.Comment: 30 pages, 19 figure

Fermi Surface and Quasiparticle Excitations of overdoped Tl2Ba2CuO6+d by ARPES

The electronic structure of the high-T_c superconductor Tl2Ba2CuO6+d is studied by ARPES. For a very overdoped Tc=30K sample, the Fermi surface consists of a single large hole pocket centered at (pi,pi) and is approaching a topological transition. Although a superconducting gap with d_x^2-y^2 symmetry is tentatively identified, the quasiparticle evolution with momentum and binding energy exhibits a marked departure from the behavior observed in under and optimally doped cuprates. The relevance of these findings to scattering, many-body, and quantum-critical phenomena is discussed.Comment: Revised manuscript, in press on PRL. A high-resolution version can be found at http://www.physics.ubc.ca/~quantmat/ARPES/PUBLICATIONS/Articles/Tl2201_LE.pdf and related material at http://www.physics.ubc.ca/~quantmat/ARPES/PUBLICATIONS/articles.htm

Unfolded Protein Response Activation Reduces Secretion and Extracellular Aggregation of Amyloidogenic Immunoglobulin Light Chain

Light-chain amyloidosis (AL) is a degenerative disease characterized by the extracellular aggregation of a destabilized amyloidogenic Ig light chain (LC) secreted from a clonally expanded plasma cell. Current treatments for AL revolve around ablating the cancer plasma cell population using chemotherapy regimens. Unfortunately, this approach is limited to the ∼70% of patients who do not exhibit significant organ proteotoxicity and can tolerate chemotherapy. Thus, identifying new therapeutic strategies to alleviate LC organ proteotoxicity should allow AL patients with significant cardiac and/or renal involvement to subsequently tolerate established chemotherapy treatments. Using a small-molecule screening approach, the unfolded protein response (UPR) was identified as a cellular signaling pathway whose activation selectively attenuates secretion of amyloidogenic LC, while not affecting secretion of a nonamyloidogenic LC. Activation of the UPR-associated transcription factors XBP1s and/or ATF6 in the absence of stress recapitulates the selective decrease in amyloidogenic LC secretion by remodeling the endoplasmic reticulum proteostasis network. Stress-independent activation of XBP1s, or especially ATF6, also attenuates extracellular aggregation of amyloidogenic LC into soluble aggregates. Collectively, our results show that stress-independent activation of these adaptive UPR transcription factors offers a therapeutic strategy to reduce proteotoxicity associated with LC aggregation

Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF

© 2016 BMJ Publishing Group Ltd & British Thoracic Society.Rationale Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberrant proliferative responses. GSK2126458 is a novel, potent, PI3K/mammalian target of rapamycin (mTOR) inhibitor which has recently completed phase I trials in the oncology setting. Our aim was to establish a scientific and dosing framework for PI3K inhibition with this agent in IPF at a clinically developable dose. Methods We explored evidence for pathway signalling in IPF lung tissue and examined the potency of GSK2126458 in fibroblast functional assays and precision-cut IPF lung tissue. We further explored the potential of IPF patient-derived bronchoalveolar lavage (BAL) cells to serve as pharmacodynamic biosensors to monitor GSK2126458 target engagement within the lung. Results We provide evidence for PI3K pathway activation in fibrotic foci, the cardinal lesions in IPF. GSK2126458 inhibited PI3K signalling and functional responses in IPF-derived lung fibroblasts, inhibiting Akt phosphorylation in IPF lung tissue and BAL derived cells with comparable potency. Integration of these data with GSK2126458 pharmacokinetic data from clinical trials in cancer enabled modelling of an optimal dosing regimen for patients with IPF. Conclusions Our data define PI3K as a promising therapeutic target in IPF and provide a scientific and dosing framework for progressing GSK2126458 to clinical testing in this disease setting. A proof-ofmechanism trial of this agent is currently underway. Trial registration number NCT01725139, pre-clinical

Contemporary and future distributions of cobia, Rachycentron canadum

Climate change has influenced the distribution and phenology of marine species, globally. However, knowledge of the impacts of climate change is lacking for many species that support valuable recreational fisheries. Cobia (Rachycentron canadum) are the target of an important recreational fishery along the U.S. east coast that is currently the subject of a management controversy regarding allocation and stock structure. Further, the current and probable future distributions of this migratory species are unclear, further complicating decision-making. The objectives of this study are to better define the contemporary distribution of cobia along the U.S. east coast and to project potential shifts in distribution and phenology under future climate change scenarios

Cartoon Computation: Quantum-like computing without quantum mechanics

We present a computational framework based on geometric structures. No quantum mechanics is involved, and yet the algorithms perform tasks analogous to quantum computation. Tensor products and entangled states are not needed -- they are replaced by sets of basic shapes. To test the formalism we solve in geometric terms the Deutsch-Jozsa problem, historically the first example that demonstrated the potential power of quantum computation. Each step of the algorithm has a clear geometric interpetation and allows for a cartoon representation.Comment: version accepted in J. Phys.A (Letter to the Editor

Accelerated Particle Swarm Optimization and Support Vector Machine for Business Optimization and Applications

Business optimization is becoming increasingly important because all business activities aim to maximize the profit and performance of products and services, under limited resources and appropriate constraints. Recent developments in support vector machine and metaheuristics show many advantages of these techniques. In particular, particle swarm optimization is now widely used in solving tough optimization problems. In this paper, we use a combination of a recently developed Accelerated PSO and a nonlinear support vector machine to form a framework for solving business optimization problems. We first apply the proposed APSO-SVM to production optimization, and then use it for income prediction and project scheduling. We also carry out some parametric studies and discuss the advantages of the proposed metaheuristic SVM.Comment: 12 page

Pharmacologic IRE1/XBP1s Activation Confers Targeted ER Proteostasis Reprogramming

Activation of the IRE1/XBP1s signaling arm of the unfolded protein response (UPR) is a promising strategy to correct defects in endoplasmic reticulum (ER) proteostasis implicated in diverse diseases. However, no pharmacologic activators of this pathway identified to date are suitable for ER proteostasis remodeling through selective activation of IRE1/XBP1s signaling. Here, we use high-throughput screening to identify non-toxic compounds that induce ER proteostasis remodeling through IRE1/XBP1s activation. We employ transcriptional profiling to stringently confirm that our prioritized compounds selectively activate IRE1/XBP1s signaling without activating other cellular stress-responsive signaling pathways. Furthermore, we demonstrate that our compounds improve ER proteostasis of destabilized variants of amyloid precursor protein (APP) through an IRE1-dependent mechanism and reduce APP-associated mitochondrial toxicity in cellular models. These results establish highly selective IRE1/XBP1s activating compounds that can be widely employed to define the functional importance of IRE1/XBP1s activity for ER proteostasis regulation in the context of health and disease. [Figure not available: see fulltext.]