Decoherence spectroscopy with individual two-level tunneling defects

Recent progress with microfabricated quantum devices has revealed that an ubiquitous source of noise originates in tunneling material defects that give rise to a sparse bath of parasitic two-level systems (TLSs). For superconducting qubits, TLSs residing on electrode surfaces and in tunnel junctions account for a major part of decoherence and thus pose a serious roadblock to the realization of solid-state quantum processors. Here, we utilize a superconducting qubit to explore the quantum state evolution of coherently operated TLSs in order to shed new light on their individual properties and environmental interactions. We identify a frequency-dependence of TLS energy relaxation rates that can be explained by a coupling to phononic modes rather than by anticipated mutual TLS interactions. Most investigated TLSs are found to be free of pure dephasing at their energy degeneracy points, around which their Ramsey and spin-echo dephasing rates scale linearly and quadratically with asymmetry energy, respectively. We provide an explanation based on the standard tunneling model, and identify interaction with incoherent low-frequency (thermal) TLSs as the major mechanism of the pure dephasing in coherent high-frequency TLS.Comment: 6 pages, 3 figures, supplementary material availabl

A logarithmic epiperimetric inequality for the obstacle problem

For the general obstacle problem, we prove by direct methods an epiperimetric inequality at regular and singular points, thus answering a question of Weiss (Invent. Math., 138 (1999), 23--50). In particular at singular points we introduce a new tool, which we call logarithmic epiperimetric inequality, which yields an explicit logarithmic modulus of continuity on the $C^1$ regularity of the singular set, thus improving previous results of Caffarelli and Monneau

Decoherence spectroscopy with individual two-level tunneling defects

Recent progress with microfabricated quantum devices has revealed that an ubiquitous source of noise originates in tunneling material defects that give rise to a sparse bath of parasitic two-level systems (TLSs). For superconducting qubits, TLSs residing on electrode surfaces and in tunnel junctions account for a major part of decoherence and thus pose a serious roadblock to the realization of solid-state quantum processors. Here, we utilize a superconducting qubit to explore the quantum state evolution of coherently operated TLSs in order to shed new light on their individual properties and environmental interactions. We identify a frequency-dependence of TLS energy relaxation rates that can be explained by a coupling to phononic modes rather than by anticipated mutual TLS interactions. Most investigated TLSs are found to be free of pure dephasing at their energy degeneracy points, around which their Ramsey and spin-echo dephasing rates scale linearly and quadratically with asymmetry energy, respectively. We provide an explanation based on the standard tunneling model, and identify interaction with incoherent low-frequency (thermal) TLSs as the major mechanism of the pure dephasing in coherent high-frequency TLS

The rs429358 locus in apolipoprotein E is associated with hepatocellular carcinoma in patients with cirrhosis

The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in apolipoprotein E (APOE), rs2642438 in mitochondrial amidoxime reducing component 1 (MARC1), rs2792751 in glycerol-3-phosphate acyltransferase (GPAM), and rs187429064 in transmembrane 6 superfamily member 2 (TM6SF2), previously associated with progressive alcohol-related and nonalcoholic fatty liver disease, are also associated with HCC. Four HCC case-control data sets were constructed, including two mixed etiology data sets (UK Biobank and FinnGen); one hepatitis C virus (HCV) cohort (STOP-HCV), and one alcohol-related HCC cohort (Dresden HCC). The frequency of each variant was compared between HCC cases and cirrhosis controls (i.e., patients with cirrhosis without HCC). Population controls were also considered. Odds ratios (ORs) associations were calculated using logistic regression, adjusting for age, sex, and principal components of genetic ancestry. Fixed-effect meta-analysis was used to determine the pooled effect size across all data sets. Across four case-control data sets, 2,070 HCC cases, 4,121 cirrhosis controls, and 525,779 population controls were included. The rs429358:C allele (APOE) was significantly less frequent in HCC cases versus cirrhosis controls (OR, 0.71; 95% confidence interval [CI], 0.61-0.84; P=2.9×10−5). Rs187429064:G (TM6SF2) was significantly more common in HCC cases versus cirrhosis controls and exhibited the strongest effect size (OR, 2.03; 95% CI, 1.45-2.86; P=3.1×10−6). In contrast, rs2792751:T (GPAM) was not associated with HCC (OR, 1.01; 95% CI, 0.90-1.13; P=0.89), whereas rs2642438:A (MARC1) narrowly missed statistical significance (OR, 0.91; 95% CI, 0.84-1.00; P=0.043). Conclusion: This study associates carriage of rs429358:C (APOE) with a reduced risk of HCC in patients with cirrhosis. Conversely, carriage of rs187429064:G in TM6SF2 is associated with an increased risk of HCC in patients with cirrhosis

Phase Ib evaluation of a self-adjuvanted protamine formulated mRNA-based active cancer immunotherapy, BI1361849 (CV9202), combined with local radiation treatment in patients with stage IV non-small cell lung cancer

Background: Preclinical studies demonstrate synergism between cancer immunotherapy and local radiation, enhancing anti-tumor effects and promoting immune responses. BI1361849 (CV9202) is an active cancer immunotherapeutic comprising protamine-formulated, sequence-optimized mRNA encoding six non-small cell lung cancer (NSCLC)-associated antigens (NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, and MUC-1), intended to induce targeted immune responses. Methods: We describe a phase Ib clinical trial evaluating treatment with BI1361849 combined with local radiation in 26 stage IV NSCLC patients with partial response (PR)/stable disease (SD) after standard first-line therapy. Patients were stratified into three strata (1: non-squamous NSCLC, no epidermal growth factor receptor (EGFR) mutation, PR/SD after ≥4 cycles of platinum- and pemetrexed-based treatment [n = 16]; 2: squamous NSCLC, PR/SD after ≥4 cycles of platinum-based and non-platinum compound treatment [n = 8]; 3: non-squamous NSCLC, EGFR mutation, PR/SD after ≥3 and ≤ 6 months EGFR-tyrosine kinase inhibitor (TKI) treatment [n = 2]). Patients received intradermal BI1361849, local radiation (4 × 5 Gy), then BI1361849 until disease progression. Strata 1 and 3 also had maintenance pemetrexed or continued EGFR-TKI therapy, respectively. The primary endpoint was evaluation of safety; secondary objectives included assessment of clinical efficacy (every 6 weeks during treatment) and of immune response (on Days 1 [baseline], 19 and 61). Results: Study treatment was well tolerated; injection site reactions and flu-like symptoms were the most common BI1361849-related adverse events. Three patients had grade 3 BI1361849-related adverse events (fatigue, pyrexia); there was one grade 3 radiation-related event (dysphagia). In comparison to baseline, immunomonitoring revealed increased BI1361849 antigen-specific immune responses in the majority of patients (84%), whereby antigen-specific antibody levels were increased in 80% and functional T cells in 40% of patients, and involvement of multiple antigen specificities was evident in 52% of patients. One patient had a partial response in combination with pemetrexed maintenance, and 46.2% achieved stable disease as best overall response. Best overall response was SD in 57.7% for target lesions. Conclusion: The results support further investigation of mRNA-based immunotherapy in NSCLC including combinations with immune checkpoint inhibitors. Trial registration: ClinicalTrials.gov, Identifier: NCT01915524