Zero-Energy Modes from Coalescing Andreev States in a Two-Dimensional Semiconductor-Superconductor Hybrid Platform

We investigate zero-bias conductance peaks that arise from coalescing subgap Andreev states, consistent with emerging Majorana zero modes, in hybrid semiconductor-superconductor wires defined in a two-dimensional InAs/Al heterostructure using top-down lithography and gating. The measurements indicate a hard superconducting gap, ballistic tunneling contact, and in-plane critical fields up to $3$~T. Top-down lithography allows complex geometries, branched structures, and straightforward scaling to multicomponent devices compared to structures made from assembled nanowires.Comment: Includes Supplementary Materia

Governing through risk: synthetic biology and the risk management process

In recent years, synthetic biology – an emerging science that promises to ‘democratize’ bioengineering – has emerged as a key site of regulatory interest and concern. In the United States, in particular, these concerns have largely been voiced in relation to synthetic biology’s perceived capacity to enable an act of bioterrorism. This thesis examines the regulatory response – a ‘risk management process’ – that has been mounted to address this contingency, and which seeks to ‘secure’ and ‘sustain’ a science characterized by sharply contrasting expectations. In particular, this thesis engages with the discursive and non-discursive practices enacted by diverse scientific and technical experts determined to assess and manage ‘risks’ that threaten to exceed the very capacity of risk, as a ‘calculative rationality’, to tame chance and legitimize responsible action. Yet, in the face of uncertainty, and in stark contrast to the ‘risk society’ thesis, this thesis underlines that uncertainty is not an inhibition to risk management, but a call for more intensive and more creative ways of organizing uncertainty, enabling action in the present. Indeed, in the case of regulating synthetic biology, risk management is, above all, tailored to finding practical ‘solutions’ to seemingly intractable policy ‘problems’. In addition to its contribution to recent scholarship that has drawn on Foucault’s concept of ‘governmentality’ to examine how diverse social problems, ranging from climate change to terrorism, are ‘governed through risk’, this thesis critically examines how biotechnology’s pairing with the perceived threat of bioterrorism is influencing the manner in which modern biology is understood, represented, practiced and controlled. Thus, the case of synthetic biology examined in this thesis not only provides a lens through which to advance risk theory in sociology, but also serves as a vector through which to explore changing configurations of ‘risk’ and ‘risk responsibility’ in the contemporary life sciences

Chester supersolid of spatially indirect excitons in double-layer semiconductor heterostructures

A supersolid, a counter-intuitive quantum state in which a rigid lattice of particles flows without resistance, has to date not been unambiguously realised. Here we reveal a supersolid ground state of excitons in a double-layer semiconductor heterostructure over a wide range of layer separations outside the focus of recent experiments. This supersolid conforms to the original Chester supersolid with one exciton per supersolid site, as distinct from the alternative version reported in cold-atom systems of a periodic modulation of the superfluid density. We provide the phase diagram augmented by the supersolid. This new phase appears at layer separations much smaller than the predicted exciton normal solid, and it persists up to a solid--solid transition where the quantum phase coherence collapses. The ranges of layer separations and exciton densities in our phase diagram are well within reach of the current experimental capabilities

Determining the date of diagnosis – is it a simple matter? The impact of different approaches to dating diagnosis on estimates of delayed care for ovarian cancer in UK primary care

Background Studies of cancer incidence and early management will increasingly draw on routine electronic patient records. However, data may be incomplete or inaccurate. We developed a generalisable strategy for investigating presenting symptoms and delays in diagnosis using ovarian cancer as an example. Methods The General Practice Research Database was used to investigate the time between first report of symptom and diagnosis of 344 women diagnosed with ovarian cancer between 01/06/2002 and 31/05/2008. Effects of possible inaccuracies in dating of diagnosis on the frequencies and timing of the most commonly reported symptoms were investigated using four increasingly inclusive definitions of first diagnosis/suspicion: 1. "Definite diagnosis" 2. "Ambiguous diagnosis" 3. "First treatment or complication suggesting pre-existing diagnosis", 4 "First relevant test or referral". Results The most commonly coded symptoms before a definite diagnosis of ovarian cancer, were abdominal pain (41%), urogenital problems(25%), abdominal distension (24%), constipation/change in bowel habits (23%) with 70% of cases reporting at least one of these. The median time between first reporting each of these symptoms and diagnosis was 13, 21, 9.5 and 8.5 weeks respectively. 19% had a code for definitions 2 or 3 prior to definite diagnosis and 73% a code for 4. However, the proportion with symptoms and the delays were similar for all four definitions except 4, where the median delay was 8, 8, 3, 10 and 0 weeks respectively. Conclusion Symptoms recorded in the General Practice Research Database are similar to those reported in the literature, although their frequency is lower than in studies based on self-report. Generalisable strategies for exploring the impact of recording practice on date of diagnosis in electronic patient records are recommended, and studies which date diagnoses in GP records need to present sensitivity analyses based on investigation, referral and diagnosis data. Free text information may be essential in obtaining accurate estimates of incidence, and for accurate dating of diagnoses

Glucose-independent Acetate Metabolism Promotes Melanoma Cell Survival and Tumor Growth

Tumors rely on multiple nutrients to meet cellular bioenergetics and macromolecular synthesis demands of rapidly dividing cells. Although the role of glucose and glutamine in cancer metabolism is well understood, the relative contribution of acetate metabolism remains to be clarified. We show that glutamine supplementation is not sufficient to prevent loss of cell viability in a subset of glucose-deprived melanoma cells, but synergizes with acetate to support cell survival. Glucose-deprived melanoma cells depend on both oxidative phosphorylation and acetate metabolism for cell survival. Acetate supplementation significantly contributed to maintenance of ATP levels in glucose-starved cells. Unlike acetate, short chain fatty acids such as butyrate and propionate failed to prevent loss of cell viability from glucose deprivation. In vivo studies revealed that in addition to nucleo-cytoplasmic acetate assimilating enzyme ACSS2, mitochondrial ACSS1 was critical for melanoma tumor growth in mice. Our data indicate that acetate metabolism may be a potential therapeutic target for BRAF mutant melanoma

Experimental conditions for observation of electron-hole superfluidity in GaAs heterostructures

The experimental parameter ranges needed to generate superfluidity in optical and drag experiments in GaAs double quantum wells are determined, using a formalism that includes self-consistent screening of the Coulomb pairing interaction in the presence of the superfluid. The very different electron and hole masses in GaAs make this a particularly interesting system for superfluidity, with exotic superfluid phases predicted in the BCS-BEC crossover regime. We find that the density and temperature ranges for superfluidity cover the range for which optical experiments have observed indications of superfluidity, but that existing drag experiments lie outside the superfluid range. However we also show that for samples with low mobility with no macroscopically connected superfluidity, if the superfluidity survived in randomly distributed localized pockets, standard quantum capacitance measurements could detect these pockets.Comment: 7 pages, 4 figure

Loss of Nmp4 optimizes osteogenic metabolism and secretion to enhance bone quality

A goal of osteoporosis therapy is to restore lost bone with structurally sound tissue. Mice lacking the transcription factor Nuclear Matrix Protein 4 (Nmp4, Zfp384, Ciz, ZNF384) respond to several classes of osteoporosis drugs with enhanced bone formation compared to wild type (WT) animals. Nmp4-/- mesenchymal stem/progenitor cells (MSPCs) exhibit an accelerated and enhanced mineralization during osteoblast differentiation. To address the mechanisms underlying this hyper-anabolic phenotype, we carried out RNA-sequencing and molecular and cellular analyses of WT and Nmp4-/- MSPCs during osteogenesis to define pathways and mechanisms associated with elevated matrix production. We determined that Nmp4 has a broad impact on the transcriptome during osteogenic differentiation, contributing to the expression of over 5,000 genes. Phenotypic anchoring of transcriptional data was performed for the hypothesis-testing arm through analysis of cell metabolism, protein synthesis and secretion, and bone material properties. Mechanistic studies confirmed that Nmp4-/- MSPCs exhibited an enhanced capacity for glycolytic conversion- a key step in bone anabolism. Nmp4-/- cells showed elevated collagen translation and secretion. Expression of matrix genes that contribute to bone material-level mechanical properties were elevated in Nmp4-/- cells, an observation that was supported by biomechanical testing of bone samples from Nmp4-/- and WT mice. We conclude that loss of Nmp4 increases the magnitude of glycolysis upon the metabolic switch, which fuels the conversion of the osteoblast into a super-secretor of matrix resulting in more bone with improvements in intrinsic quality