Doctor of Philosophy

dissertationT lymphocyte-derived malignancies are pediatric cancers often carrying poor prognoses. The proto-oncogenes underlying these malignancies frequently are also fundamental to normal lymphocyte development and function. Therefore, the discovery of heretofore unrecognized lymphocyte oncogenes and tumor suppressors is of potentially profound significance to both clinical medicine and scientific understanding. To address this, we pioneered a phenotype-driven forward-genetic screen in zebrafish (Danio rerio). Using transgenic animals with T lymphocyte-specific enhanced green fluorescent protein (EGFP), we performed chemical mutagenesis, screened fish for GFP+ tumors, and identified several lines developing heritable T cell malignancies. One of these lines, oscar the grouch (otg), is characterized by recessive inheritance. Validation of otg as a true leukemia predisposition model was accomplished using histology, immunohistochemistry, gene expression studies, confirmation of clonality, and allogeneic transplantation. In search of the genetic mutation underlying otg, we compared in vivo responses to glucocorticoids and γ-irradiation (therapies known to affect human T-ALL). Both dexamethasone (DXM) and irradiation treatment (XRT) were of limited or no utility in otg. In addition to diminished sensitivity, otg larvae were resistant to radiation-induced apoptosis and showed decreased activation of caspase 3. We determined this resistance is due to a block in the intrinsic mitochondrial apoptosis pathway. To discover genetic changes that may cause T-ALL, and those contributing to relapse, we used array comparative genomic hybridization (aCGH) in both humans and zebrafish. We identified copy number aberrations (CNAs) in 17 zebrafish T-ALLs, and compared all D. rerio genes found in any CNA to a cohort of 75 human T-ALL samples. We found significant overlap (62%) with genes in CNAs from the human T-ALLs. Additionally, 15 genes recurrently altered (≥3 samples) in zebrafish T-ALL were also in CNAs from 5 or more human T-ALLs. Finally, we used aCGH to study CNA genes acquired during iterative allo-transplantations of 3 zebrafish malignancies. We compared these genes with human aCGH results from 23 patients who either failed induction, or had already relapsed. Again, we observed a large overlap (53%) as well as 9 genes found in 2 fish and ≥5 humans. These genes are candidates for causing the increased severity of these tumors

Landau Level Collapse in Gated Graphene Structures

We describe a new regime of magnetotransport in two dimensional electron systems in the presence of a narrow potential barrier imposed by external gates. In such systems, the Landau level states, confined to the barrier region in strong magnetic fields, undergo a deconfinement transition as the field is lowered. We present transport measurements showing Shubnikov-de Haas (SdH) oscillations which, in the unipolar regime, abruptly disappear when the strength of the magnetic field is reduced below a certain critical value. This behavior is explained by a semiclassical analysis of the transformation of closed cyclotron orbits into open, deconfined trajectories. Comparison to SdH-type resonances in the local density of states is presented.Comment: 4 pages, 2 figure

Topological characterization of periodically-driven quantum systems

Topological properties of physical systems can lead to robust behaviors that are insensitive to microscopic details. Such topologically robust phenomena are not limited to static systems but can also appear in driven quantum systems. In this paper, we show that the Floquet operators of periodically driven systems can be divided into topologically distinct (homotopy) classes, and give a simple physical interpretation of this classification in terms of the spectra of Floquet operators. Using this picture, we provide an intuitive understanding of the well-known phenomenon of quantized adiabatic pumping. Systems whose Floquet operators belong to the trivial class simulate the dynamics generated by time-independent Hamiltonians, which can be topologically classified according to the schemes developed for static systems. We demonstrate these principles through an example of a periodically driven two--dimensional hexagonal lattice model which exhibits several topological phases. Remarkably, one of these phases supports chiral edge modes even though the bulk is topologically trivial.Comment: 9 Pages + Appendi

Topological transition of a non-Markovian dissipative quantum walk

We extend non-Hermitian topological quantum walks on a Su-Schrieffer-Heeger (SSH) lattice [M. S. Rudner and L. Levitov, Phys. Rev. Lett. 102, 065703 (2009)] to the case of non-Markovian evolution. This non-Markovian model is established by coupling each unit cell in the SSH lattice to a reservoir formed by a quasi-continuum of levels. We find a topological transition in this model even in the case of non-Markovian evolution, where the walker may visit the reservoir and return to the SSH lattice at a later time. The existence of a topological transition does, however, depend on the low-frequency properties of the reservoir, characterized by a spectral density $J(\epsilon)\propto |\epsilon|^\alpha$. In particular, we find a robust topological transition for a sub-Ohmic ($\alpha<1$) and Ohmic ($\alpha=1$) reservoir, but no topological transition for a super-Ohmic ($\alpha>1$) reservoir. This behavior is directly related to the well-known localization transition for the spin-boson model. We confirm the presence of non-Markovian dynamics by explicitly evaluating a measure of Markovianity for this model.Comment: 10 pages, 4 figures; v2: Minor changes to address referee comment

Concurrent affective and linguistic prosody with the same emotional valence elicits a late positive ERP response

Change in linguistic prosody generates a mismatch negativity response (MMN), indicating neural representation of linguistic prosody, while change in affective prosody generates a positive response (P3a), reflecting its motivational salience. However, the neural response to concurrent affective and linguistic prosody is unknown. The present paper investigates the integration of these two prosodic features in the brain by examining the neural response to separate and concurrent processing by electroencephalography (EEG). A spoken pair of Swedish words—[ˈfɑ́ːsɛn] phase and [ˈfɑ̀ːsɛn] damn—that differed in emotional semantics due to linguistic prosody was presented to 16 subjects in an angry and neutral affective prosody using a passive auditory oddball paradigm. Acoustically matched pseudowords—[ˈvɑ́ːsɛm] and [ˈvɑ̀ːsɛm]—were used as controls. Following the constructionist concept of emotions, accentuating the conceptualization of emotions based on language, it was hypothesized that concurrent affective and linguistic prosody with the same valence—angry [ˈfɑ̀ːsɛn] damn—would elicit a unique late EEG signature, reflecting the temporal integration of affective voice with emotional semantics of prosodic origin. In accordance, linguistic prosody elicited an MMN at 300–350 ms, and affective prosody evoked a P3a at 350–400 ms, irrespective of semantics. Beyond these responses, concurrent affective and linguistic prosody evoked a late positive component (LPC) at 820–870 ms in frontal areas, indicating the conceptualization of affective prosody based on linguistic prosody. This study provides evidence that the brain does not only distinguish between these two functions of prosody but also integrates them based on language and experience

Nuclear Spin Dynamics in Double Quantum Dots: Fixed Points, Transients, and Intermittency

Transport through spin-blockaded quantum dots provides a means for electrical control and detection of nuclear spin dynamics in the host material. Although such experiments have become increasingly popular in recent years, interpretation of their results in terms of the underlying nuclear spin dynamics remains challenging. Here we point out a fundamental process in which nuclear spin dynamics can be driven by electron shot noise; fast electric current fluctuations generate much slower nuclear polarization dynamics, which in turn affect electron dynamics via the Overhauser field. The resulting extremely slow intermittent current fluctuations account for a variety of observed phenomena that were not previously understood.Comment: version accepted for publication in Physical Review B, figure repaire

Klein Backscattering and Fabry-Perot Interference in Graphene Heterojunctions

We present a theory of quantum-coherent transport through a lateral p-n-p structure in graphene, which fully accounts for the interference of forward and backward scattering on the p-n interfaces. The backreflection amplitude changes sign at zero incidence angle because of the Klein phenomenon, adding a phase $\pi$ to the interference fringes. The contributions of the two p-n interfaces to the phase of the interference cancel with each other at zero magnetic field, but become imbalanced at a finite field. The resulting half a period shift in the Fabry-Perot fringe pattern, induced by a relatively weak magnetic field, can provide a clear signature of Klein scattering in graphene. This effect is shown to be robust in the presence of spatially inhomogeneous potential of moderate strength.Comment: 5 pgs, 4 fg

Quantum Phase Tomography of a Strongly Driven Qubit

The interference between repeated Landau-Zener transitions in a qubit swept through an avoided level crossing results in Stueckelberg oscillations in qubit magnetization. The resulting oscillatory patterns are a hallmark of the coherent strongly-driven regime in qubits, quantum dots and other two-level systems. The two-dimensional Fourier transforms of these patterns are found to exhibit a family of one-dimensional curves in Fourier space, in agreement with recent observations in a superconducting qubit. We interpret these images in terms of time evolution of the quantum phase of qubit state and show that they can be used to probe dephasing mechanisms in the qubit.Comment: 5 pgs, 4 fg

Postmortem Changes in Myoglobin Content in Organs

Postmortem changes in myoglobin concentrations in blood and organs were investigated using an enzyme immunoassay by animal experiments in combination with immunohistochemical staining of human cases. Blood myoglobin concentrations were found to increase drastically within a very short time after death. Those in striated muscle, however, did not change by day 14 postmortem. Myoglobin content in the liver and kidney increased slightly by day 5 postmortem, and more obviously by day 7 or later. However, almost no change was observed by day 5 in the kidney when the renal artery and vein had been ligated just after death. In the thyroid gland and the lung, the myoglobin content markedly increased by day 7 postmortem, with the logarithmical values rising nearly linearly as the time after death passed. In the thyroid gland, concentrations reached the level of the striated muscle. The mechanisms of postmortem myoglobin increase in organs are thought to be direct diffusion from the striated muscle and/or distribution through the blood. To estimate the postmortem interval, the determination of myoglobin content in the thyroid gland or the lung appears to be useful