A comparison of Margaret Atwood\u27s dystopian text, The Handmaid\u27s tale, and Catherine Helen Spence\u27s utopian text, Handfasted

The two texts which have been compared in this thesis are Handfasted written by the South Australian author Catherine Helen Spence and The Handmaid\u27s Tale written by the Canadian author Margaret Atwood. Although written nearly one hundred years apart both books follow the tradition of the Utopian genre, although Spence\u27s attitude to the future is much more optimistic than Atwood\u27s. Spence creates a Utopia in her fictional American Columba where the inhabitants, male and female, experience religious and social tolerance. The radical practice of handfasting has given the inhabitants of Columba freedom to change sexual partners every year if they are not satisfied and any children from the union of handfasted parents are privileged in Columba. They are the only ones who are taught to read and write and form the bureaucracy of the Plantation of Columba. Atwood, on the other hand, has created the dystopian Republic of Gilead where any aberrations from the religious and social practices of this mythical American society are brutally punished. The inhabitants of Gilead are ruled by fear and there is not even the pretence of equality in Gilead. Women are required to be silent and, to guarantee that silence, they are under constant surveillance

Creation, Destruction, and the Tension Between: A Cautionary Note on Individuation in Tristan Egolf, W. G. Sebald, and Niall Williams

The modern individual faces a psychological disconnect between his conscious mind and unconscious due primarily to the outward attachments that dictate false tenets of ontological worth. This thesis investigates the benchmark of creation and destruction and narrows in on its utility in the individual’s pursuit for individuation. The creation and destruction paradox is used to penetrate liminal space where personal transformation occurs, and it is used within those spaces to strip away old, ego-centric ideals in the service of new ones. C. G. Jung’s “archetypes of transformation” are the main tools of the psyche for assisting the conscious mind to engage in open discourse with the unconscious. Uroboric archetypes such as the Great Mother, and projected archetypal figure such as Kali the Devouring Mother, are explored within the contemporary novels of Tristan Egolf, W. G. Sebald, and Niall Williams. The unconscious projects destructive archetypes to destroy the conscious mind’s unhealthy ideologies. By sifting through the rubble of our immediate and shattered past, the individual can create the cornerstones of new philosophies that promote psychological wholeness. Once the individual establishes equilibrium of creation and destruction and, subsequently, of his psyche, individuation is achieved. Psychological wholeness leads to individual self-worth, confidence, purpose, and a sense of belonging in the universe

Homologous recombination: from model organisms to human disease

Recent experiments show that properly controlled recombination between homologous DNA molecules is essential for the maintenance of genome stability and for the prevention of tumorigenesis

Robust shaped pulses for arrays of superconducting or semiconductor spin qubits with fixed Ising coupling

A major current challenge in solid-state quantum computing is to scale qubit arrays to a larger number of qubits. This is hampered by the complexity of the control wiring for the large number of independently tunable interqubit couplings within these arrays. One approach to simplifying the problem is to use a qubit array with fixed Ising ($ZZ$) interactions. When simultaneously driving a specific subset of qubits in such a system, the dynamics are confined to a set of commuting $\mathfrak{su}$(2) subalgebras. Within these $\mathfrak{su}$(2)s we describe how to perform $X$-gates and $\frac{\pi}{2}$ $ZZ$ rotations robustly against either leakage, which is the main source of error in transmon qubits, or coupling fluctuations, which is the main source of infidelity in flux or semiconductor spin qubits. These gates together with virtual-$z$ gates form a universal set of gates for quantum computing. We construct this set of robust gates for two-edge, three-edge, and four-edge vertices, which compose all existing superconducting qubit and semiconductor spin qubit arrays.Comment: 9 pages, 6 figure

The effect of thermal dose on hyperthermia-mediated inhibition of DNA repair through homologous recombination

Hyperthermia has a number of biological effects that sensitize tumors to radiotherapy in the range between 40-44 °C. One of these effects is heat-induced degradation of BRCA2 that in turn causes reduced RAD51 focus formation, which results in an attenuation of DNA repair through homologous recombination. Prompted by this molecular insight into how hyperthermia attenuates homologous recombination, we now quantitatively explore time and temperature dynamics of hyperthermia on BRCA2 levels and RAD51 focus formation in cell culture models, and link this to their clonogenic survival capacity after irradiation (0-6 Gy). For treatment temperatures above 41 °C, we found a decrease in cell survival, an increase in sensitization towards irradiation, a decrease of BRCA2 protein levels, and altered RAD51 focus formation. When the temperatures exceeded 43 °C, we found that hyperthermia alone killed more cells directly, and that processes other than homologous recombination were affected by the heat. This study demonstrates that optimal inhibition of HR is achieved by subjecting cells to hyperthermia at 41-43 °C for 30 to 60 minutes. Our data provides a guideline for the clinical application of novel combination treatments that could exploit hyperthermia's attenuation of homologous recombination, such as the combination of hyperthermia with PARP-inhibitors for non-BRCA mutations carriers

Nonadiabatic quantum control of quantum dot arrays with fixed exchange using Cartan decomposition

In semiconductor spin qubits which typically interact through short-range exchange coupling, shuttling of spin is a practical way to generate quantum operations between distant qubits. Although the exchange is often tunable through voltages applied to gate electrodes, its minimal value can be significantly large, which hinders the applicability of existing shuttling protocols to such devices, requiring a different approach. In this work, we extend our previous results for double- and triple-dot systems, and describe a method for implementing spin shuttling in long chains of quantum dots in a nonadiabatic manner. We make use of Cartan decomposition to break down the interacting problem into simpler problems in a systematic way, and use dynamical invariants to design smooth nonadiabatic pulses that can be implemented in devices with modest control bandwidth. Finally, we discuss the extensibility of our results to directed shuttling of spin states on two-dimensional lattices of quantum dots with fixed coupling.Comment: 10 pages and 4 figure

Differential Dynamics of ATR-Mediated Checkpoint Regulators

The ATR-Chk1 checkpoint pathway is activated by UV-induced DNA lesions and replication stress. Little was known about the spatio and temporal behaviour of the proteins involved, and we, therefore, examined the behaviour of the ATRIP-ATR and Rad9-Rad1-Hus1 putative DNA damage sensor complexes and the downstream effector kinase Chk1. We developed assays for the generation and validation of stable cell lines expressing GFP-fusion proteins. Photobleaching experiments in living cells expressing these fusions indicated that after UV-induced DNA damage, ATRIP associates more transiently with damaged chromatin than members of the Rad9-Rad1-Hus1 complex. Interestingly, ATRIP directly associated with locally induced UV damage, whereas Rad9 bound in a cooperative manner, which can be explained by the Rad17-dependent loading of Rad9 onto damaged chromatin. Although Chk1 dissociates from the chromatin upon UV damage, no change in the mobility of GFP-Chk1 was observed, supporting the notion that Chk1 is a highly dynamic protein

DNA damage-inducing anticancer therapies: From global to precision damage

DNA damage-inducing therapies are of tremendous value for cancer treatment and function by the direct or indirect formation of DNA lesions and subsequent inhibition of cellular proliferation. Of central importance in the cellular response to therapy-induced DNA damage is the DNA damage response (DDR), a protein network guiding both DNA damage repair and the induction of cancer-e

Synergistic Roles of Non-Homologous End Joining and Homologous Recombination in Repair of Ionizing Radiation-Induced DNA Double Strand Breaks in Mouse Embryonic Stem Cells

DNA double strand breaks (DSBs) are critical for the efficacy of radiotherapy as they lead to cell death if not repaired. DSBs caused by ionizing radiation (IR) initiate histone modifications and accumulate DNA repair proteins, including 53BP1, which forms distinct foci at damage sites and serves as a marker for DSBs. DSB repair primarily occurs through Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR). NHEJ directly ligates DNA ends, employing proteins such as DNA-PKcs, while HR, involving proteins such as Rad54, uses a sister chromatid template for accurate repair and functions in the S and G2 phases of the cell cycle. Both pathways are crucial, as illustrated by the IR sensitivity in cells lacking DNA-PKcs or Rad54. We generated mouse embryonic stem (mES) cells which are knockout (KO) for DNA-PKcs and Rad54 to explore the combined role of HR and NHEJ in DSB repair. We found that cells lacking both DNA-PKcs and Rad54 are hypersensitive to X-ray radiation, coinciding with impaired 53BP1 focus resolution and a more persistent G2 phase cell cycle block. Additionally, mES cells deficient in DNA-PKcs or both DNA-PKcs and Rad54 exhibit an increased nuclear size approximately 18–24 h post-irradiation. To further explore the role of Rad54 in the absence of DNA-PKcs, we generated DNA-PKcs KO mES cells expressing GFP-tagged wild-type (WT) or ATPase-defective Rad54 to track the Rad54 foci over time post-irradiation. Cells lacking DNA-PKcs and expressing ATPase-defective Rad54 exhibited a similar phenotypic response to IR as those lacking both DNA-PKcs and Rad54. Despite a strong G2 phase arrest, live-cell imaging showed these cells eventually progress through mitosis, forming micronuclei. Additionally, mES cells lacking DNA-PKcs showed increased Rad54 foci over time post-irradiation, indicating an enhanced reliance on HR for DSB repair without DNA-PKcs. Our findings underscore the essential roles of HR and NHEJ in maintaining genomic stability post-IR in mES cells. The interplay between these pathways is crucial for effective DSB repair and cell cycle progression, highlighting potential targets for enhancing radiotherapy outcomes.</p

Contributions of supercoiling to Tn3 resolvase and phage Mu Gin site-specific recombination

Members of the resolvase/invertase family of site-specific recombinases require supercoiled substrates containing two recombination sites. To dissect the roles of supercoiling in recombination by the Tn3 and γδ resolvases and the phage Mu Gin invertase, we used substrates that provided some but not all of the topological features of the standard substrate. We divided the Tn3 resolvase reaction into two stages, synapsis and postsynapsis. We found the contributions of supercoiling to each stage were distinct, since substrate catenation in the absence of supercoiling or low levels of substrate supercoiling were sufficient for synapsis but not postsynapsis. Using structural and functional topological analyses, we verified that the resolvase synaptic complexes with nicked catenanes were recombination intermediates. The requirement for supercoiling was even less stringent for the γδ resolvase, which recombined nicked catenanes about half as well as it did supercoiled substrates. Gin recombination of catenanes occurred even if the recombinational enhancer was on a nicked ring, as long as both crossover sites were on a supercoiled ring. Therefore, supercoiling is required at the Gin crossover sites but not at the enhancer. We conclude that solely conformational effects of supercoiling are required for resolvase synapsis and the function of the Gin enhancer, but that a torsional effect, probably double helix unwinding, is needed for Tn3 resolvase postsynapsis and at the Gin recombination sites