Microwave parametric amplifiers based on Josephson junctions have become a key component of many quantum information experiments. One key limitation which has not been well predicted by theory is the gain saturation behavior which determines its ability to process large amplitude signals. The typical explanation for this behavior in phase-preserving amplifiers based on three-wave mixing is pump depletion, in which the consumption of pump photons to produce amplification results in a reduction in gain. However, in this work we present experimental data and theoretical calculations showing that the fourth-order Kerr nonlinearities inherent in the Josephson junctions are the dominant factor in the Josephson Parametric Converter (JPC). The Kerr-based theory has the unusual property of causing saturation to both lower and higher gains, depending on bias conditions. This work presents a new methodology for optimizing device performance in the presence of Kerr nonlinearities while retaining device tunability, and points to the necessity of controlling higher-order Hamiltonian terms to make further improvements in parametric devices.Comment: 5 pages, 4 figure

Serial changes in glomerular capillary loop gene expression were used to uncover mechanisms contributing to primary glomerular disease in rat models of passive Heymann nephritis and puromycin nephrosis. Before the onset of proteinuria, podocyte protein-tyrosine phosphatase (GLEPP1) expression was transiently decreased in the nephrosis model, whereas the immune costimulatory molecule B7.1 was stimulated in both models. To relate these changes to the development of proteinuria, the time of onset and intensity of proteinuria were altered. When the models were induced simultaneously, proteinuria and anasarca occurred earlier with the collapse of glomerular capillary loops. Upregulation of B7.1 with the downregulation of GLEPP1, Wilms' tumor gene (WT1), megalin, and vascular endothelial growth factor started early and persisted through the course of disease. In the puromycin and the combined models, changes in GLEPP1 expression were corticosteroid-sensitive, whereas B7.1, WT1, vascular endothelial growth factor, and most slit diaphragm genes involved later in the combined model, except podocin, were corticosteroid-resistant. There was a very early increase in the nuclear expression of podocyte transcription factors ZHX2 and ZHX1 that may be linked to the changes in gene expression in the combined proteinuric model. Our studies suggest that an early and persistent change in mostly steroid-resistant glomerular gene expression is the hallmark of severe and progressive glomerular disease.

Josephson-junction based parametric amplifiers have become a ubiquitous component in superconducting quantum machines. Although parametric amplifiers regularly achieve near-quantum limited performance, they have many limitations, including low saturation powers, lack of directionality, and narrow bandwidth. The first is believed to stem from the higher order Hamiltonian terms endemic to Josephson junction circuits, and the latter two are direct consequences of the nature of the parametric interactions which power them. In this work, we attack both of these issues. First, we have designed a new, linearly shunted Josephson Ring Modulator (JRM) which nearly nulls all 4th-order terms at a single flux bias point. Next, we achieve gain through a pair of balanced parametric drives. When applied separately, these drives produce phase-preserving gain (G) and gainless photon conversion (C), when applied together, the resultant amplifier (which we term GC) is a bi-directional, phase-sensitive transmission-only amplifier with a large, gain-independent bandwidth. Finally, we have also demonstrated the practical utility of the GC amplifier, as well as its' quantum efficiency, by using it to read out a superconducting transmon qubit.

4530 Background: EAC has eluded cure even with platin-based CRT. Stratifying pts by likelihood of success is one approach to improving outcomes. We assessed whether SNPs in DNA repair paths are associated with complete pathologic response (pCR) in EAC pts who received C-based CRT followed by surgery. Methods: Patients and specimens: Pretreatment biopsy or post-CRT resection samples were obtained from pts (EAC, stage II-IVa) treated on a randomized phase II trial, E1201 (n=86), of preop CRT (RT to 45 Gy). Arm A: Preop C 30 mg/m2 + irinotecan (I) 50 mg/m2 days (d) 1, 8, 22, 29 with RT. Post-op C 30 mg/m2 + I 65 mg/m2 d 1, 8 q21 days x 3. Arm B: Preop C 30 mg/m2 + paclitaxel (P) 50 mg/m2 d 1, 8, 15, 22, 29 with RT. Post-op C 75 mg/m2 + P 175 mg/m2 d 1 q21 days x 3. Clinical outcome - pCR: (A) 14% [95% CI 5.5%, 28.5%]; (B) 16% [95% CI 6.7%, 30.1%]. Median overall survival (OS): (A) 34.9 m (months) [90% CI 23.5, not reached]; (B) 20.9 m [90% CI 17.4, 46.7]. Experimental procedure: Normal tissue was microdissected from unstained sections of paraffin-embedded tissue. DNA was extracted (Qiagen). Genotyping was performed by matrix-assisted laser desorption/ionization time-of-flight (Sequenom) for all SNPs. Each SNP was dichotomized a priori into: (1) major homozygote vs (2) minor (heterozygote plus minor homozygote) allele groups. Data analysis was performed centrally, with lab investigators blinded to clinical data. Exact logistic regression was used to derive ORs for non-pCR, using the major homozygote as the reference (2-sided p values). Results: Germline DNA was available in 68 pts; 60 were eligible and began therapy ( Table ). Conclusions: In this homogenous, well-defined cohort, the XRCC1 Arg399Gln minor allele group was associated with lower pCR (p=0.06). Lab data on a panel of additional SNPs have been collected and are under analysis for presentation at the meeting. [Table: see text] [Table: see text]