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Recently, great progress has been made in the field of ultrasensitive microwave detectors, reaching even the threshold for utilization in circuit quantum electrodynamics. However, cryogenic sensors lack the compatibility with broad-band metrologically traceable power absorption measurements at ultralow powers, which restricts their range of applications. Here, we demonstrate such measurements using an ultralow-noise nanobolometer, which we extend by an additional direct-current (dc) heater input. The tracing of the absorbed power relies on comparing the response of the bolometer between radio frequency and dc-heating powers traced to the Josephson voltage and quantum Hall resistance. To illustrate this technique, we demonstrate two different methods of dc-substitution to calibrate the power that is delivered to the base temperature stage of a dilution refrigerator using our in situ power sensor. As an example, we demonstrate the ability to accurately measure the attenuation of a coaxial input line between the frequencies of 50 MHz and 7 GHz with an uncertainty down to 0.1 dB at a typical input power of -114 dBm.
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Radiation sensors based on the heating effect of absorbed radiation are typically simple to operate and flexible in terms of input frequency, so they are widely used in gas detection1, security2, terahertz imaging3, astrophysical observations4 and medical applications5. Several important applications are currently emerging from quantum technology and especially from electrical circuits that behave quantum mechanically, that is, circuit quantum electrodynamics6. This field has given rise to single-photon microwave detectors7-9 and a quantum computer that is superior to classical supercomputers for certain tasks10. Thermal sensors hold potential for enhancing such devices because they do not add quantum noise and they are smaller, simpler and consume about six orders of magnitude less power than the frequently used travelling-wave parametric amplifiers11. However, despite great progress in the speed12 and noise levels13 of thermal sensors, no bolometer has previously met the threshold for circuit quantum electrodynamics, which lies at a time constant of a few hundred nanoseconds and a simultaneous energy resolution of the order of 10h gigahertz (where h is the Planck constant). Here we experimentally demonstrate a bolometer that operates at this threshold, with a noise-equivalent power of 30 zeptowatts per square-root hertz, comparable to the lowest value reported so far13, at a thermal time constant two orders of magnitude shorter, at 500 nanoseconds. Both of these values are measured directly on the same device, giving an accurate estimation of 30h gigahertz for the calorimetric energy resolution. These improvements stem from the use of a graphene monolayer with extremely low specific heat14 as the active material. The minimum observed time constant of 200 nanoseconds is well below the dephasing times of roughly 100 microseconds reported for superconducting qubits15 and matches the timescales of currently used readout schemes16,17, thus enabling circuit quantum electrodynamics applications for bolometers.
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Superconducting coplanar-waveguide (CPW) resonators are one of the key devices in circuit quantum electrodynamics (cQED). Their performance can be limited by dielectric losses in the substrate and in the material interfaces. Reliable modeling is required to aid in the design of low-loss CPW structures for cQED. We analyze the geometric dependence of the dielectric losses in CPW structures using finite-element modeling of the participation ratios of the lossy regions. In a practical scenario, uncertainties in the the dielectric constants and loss tangents of these regions introduce uncertainties in the theoretically predicted participation ratios. We present a method for combining loss simulations with measurements of two-level-system-limited quality factors and resonance frequencies of CPW resonators. Namely, we solve an inverse problem to find model parameters producing the measured values. High quality factors are obtainable by properly designing the cross-sectional geometries of the CPW structures, but more accurate modeling and design methods for low-loss CPW resonators are called for major future improvements. Our nonlinear optimization methodology for solving the aforementioned inverse problem is a step in this direction.
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We experimentally study the dynamics of quantum knots in a uniform magnetic field in spin-1 Bose-Einstein condensates. The knot is created in the polar magnetic phase, which rapidly undergoes a transition toward the ferromagnetic phase in the presence of the knot. The magnetic order becomes scrambled as the system evolves, and the knot disappears. Strikingly, over long evolution times, the knot decays into a polar-core spin vortex, which is a member of a class of singular SO(3) vortices. The polar-core spin vortex is stable with an observed lifetime comparable to that of the condensate itself. The structure is similar to that predicted to appear in the evolution of an isolated monopole defect, suggesting a possible universality in the observed topological transition.
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Persistent topological defects and textures are particularly dramatic consequences of superfluidity. Among the most fascinating examples are the singular vortices arising from the rotational symmetry group SO(3), with surprising topological properties illustrated by Dirac's famous belt trick. Despite considerable interest, controlled preparation and detailed study of vortex lines with complex internal structure in fully three-dimensional spinor systems remains an outstanding experimental challenge. Here, we propose and implement a reproducible and controllable method for creating and detecting a singular SO(3) line vortex from the decay of a non-singular spin texture in a ferromagnetic spin-1 Bose-Einstein condensate. Our experiment explicitly demonstrates the SO(3) character and the unique spinor properties of the defect. Although the vortex is singular, its core fills with atoms in the topologically distinct polar magnetic phase. The resulting stable, coherent topological interface has analogues in systems ranging from condensed matter to cosmology and string theory.
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Superconducting microwave circuits show great potential for practical quantum technological applications such as quantum information processing. However, fast and on-demand initialization of the quantum degrees of freedom in these devices remains a challenge. Here, we experimentally implement a tunable heat sink that is potentially suitable for the initialization of superconducting qubits. Our device consists of two coupled resonators. The first resonator has a high quality factor and a fixed frequency whereas the second resonator is designed to have a low quality factor and a tunable resonance frequency. We engineer the low quality factor using an on-chip resistor and the frequency tunability using a superconducting quantum interference device. When the two resonators are in resonance, the photons in the high-quality resonator can be efficiently dissipated. We show that the corresponding loaded quality factor can be tuned from above 105 down to a few thousand at 10 GHz in good quantitative agreement with our theoretical model.
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AIM: For previously untreated patients (PUPs) with severe haemophilia A in Finland for the past 2 decades, the standard practice has been to start early primary prophylaxis. We evaluated the long-term clinical outcomes and costs of treatment with high-dose prophylaxis in PUPs from birth to adolescence, including immune tolerance induction (ITI). METHODS: From the medical records of all PUPs born between June 1994 and May 2013 in Finland, we retrospectively extracted data on clinical outcomes and healthcare use. Using linear mixed models, we analysed longitudinal clinical outcome data. To analyse skewed cost data, including zero costs, we applied hurdle regression. RESULTS: All 62 patients received early regular prophylaxis; totally, they have had treatment for nearly 700 patient-years. The median age of starting home treatment was 1.1 years. The mean (SD) annual treatment costs ( per kg) were 4391 (3852). For ages 1-3, ITI comprised over half of the costs; in other groups, prophylactic FVIII treatment dominated. With these high costs, however, clinical outcomes were desirable; median (IQR) ABR was low at 0.19 (0.07-0.46) and so was AJBR at 0.06 (0-0.24). Thirteen (21%) patients developed a clinically significant inhibitor, 10 (16%) with a high titre. All ITIs were successful. The mean costs for ITI were 383 448 (259 085). The expected ITI payback period was 1.81 (95% CI 0.62-12.12) years. CONCLUSIONS: Early high-dose prophylaxis leads to excellent long-term clinical outcomes, and early childhood ITI therapy seems to turn cost-neutral generally already in 2 years.
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Hemofilia A/tratamento farmacológico , Hemofilia A/economia , Adolescente , Criança , Pré-Escolar , Documentação , Fator VIII/economia , Fator VIII/imunologia , Fator VIII/uso terapêutico , Feminino , Finlândia , Custos de Cuidados de Saúde/estatística & dados numéricos , Hemofilia A/imunologia , Humanos , Tolerância Imunológica , Lactente , Recém-Nascido , Masculino , Resultado do TratamentoRESUMO
Mitochondria produce adenosine triphosphate (ATP) for energy requirements via the mitochondrial oxidative phosphorylation (OXPHOS) system. One of the hallmarks of cancer is the energy shift toward glycolysis. Low OXPHOS activity and increased glycolysis are associated with aggressive types of cancer. Mitochondria have their own genome (mitochondrial DNA [mtDNA]) encoding for 13 essential subunits of the OXPHOS enzyme complexes. We studied mtDNA in childhood acute lymphoblastic leukemia (ALL) to detect potential pathogenic mutations in OXPHOS complexes. The whole mtDNA from blood and bone marrow samples at diagnosis and follow-up from 36 ALL patients were analyzed. Novel or previously described pathogenic mtDNA mutations were identified in 8 out of 36 patients. Six out of these 8 patients had died from ALL. Five out of 36 patients had an identified poor prognosis genetic marker, and 4 of these patients had mtDNA mutations. Missense or nonsense mtDNA mutations were detected in the genes encoding subunits of OXPHOS complexes, as follows: MT-ND1, MT-ND2, MT-ND4L and MT-ND6 of complex I; MT-CO3 of complex IV; and MT-ATP6 and MT-ATP8 of complex V. We discovered mtDNA mutations in childhood ALL supporting the hypothesis that non-neutral variants in mtDNA affecting the OXPHOS function may be related to leukemic clones.
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Complexo I de Transporte de Elétrons/genética , ATPases Mitocondriais Próton-Translocadoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Trifosfato de Adenosina/genética , Adolescente , Criança , Pré-Escolar , DNA Mitocondrial/genética , Feminino , Genoma Mitocondrial/genética , Glicólise/genética , Humanos , Lactente , Masculino , Mitocôndrias/genética , Mutação/genética , Fosforilação Oxidativa , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
Inherited bone marrow failure syndromes (IBMFS) are group of disorders that lead to inadequate production of blood cells. Mutations in genes involved in telomere maintenance, DNA repair, and the cell cycle cause IBMFS. ERCC6L2 gene mutations have been associated with bone marrow failure that includes developmental delay and microcephaly. We report 2 cases of bone marrow failure with no extra-hematopoietic manifestations in patients from unrelated families with a homozygous truncating mutation in ERCC6L2. Bone marrow failure without developmental delay or microcephaly with ERCC6L2 mutation has not been previously described.
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Anemia Aplástica/genética , Doenças da Medula Óssea/genética , DNA Helicases/genética , Hemoglobinúria Paroxística/genética , Microcefalia/genética , Malformações do Sistema Nervoso/genética , Adolescente , Anemia Aplástica/fisiopatologia , Doenças da Medula Óssea/fisiopatologia , Transtornos da Insuficiência da Medula Óssea , Criança , Reparo do DNA/genética , Feminino , Mutação da Fase de Leitura/genética , Hemoglobinúria Paroxística/fisiopatologia , Homozigoto , Humanos , Masculino , Microcefalia/fisiopatologia , Malformações do Sistema Nervoso/fisiopatologiaRESUMO
We experimentally investigate and utilize electrothermal feedback in a microwave nanobolometer based on a normal-metal (Au_{x}Pd_{1-x}) nanowire with proximity-induced superconductivity. The feedback couples the temperature and the electrical degrees of freedom in the nanowire, which both absorbs the incoming microwave radiation, and transduces the temperature change into a radio-frequency electrical signal. We tune the feedback in situ and access both positive and negative feedback regimes with rich nonlinear dynamics. In particular, strong positive feedback leads to the emergence of two metastable electron temperature states in the millikelvin range. We use these states for efficient threshold detection of coherent 8.4 GHz microwave pulses containing approximately 200 photons on average, corresponding to 1.1×10^{-21} J≈7.0 meV of energy.
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INTRODUCTION: Currently the most serious treatment complication of haemophilia is the inhibitor development (ID), i.e. neutralizing antibody development. AIM: This nationwide multicentre study in Finland evaluated the incidence and risk factors of ID in previously untreated patients (PUPs) with severe haemophilia A (FVIII:C < 0.01 IU mL(-1) ). METHODS: We enrolled all PUPs (N = 62) born between June 1994 and May 2013 with at least 75 exposure days (EDs) to screen ID during follow-up extending to September 2013. RESULTS: Thirteen ID (21% of 62) occurred; 10 (16% of 62) with high titre. Fifty-one patients (82%) were on primary prophylaxis (regular prophylaxis before the age of 2 and before the first joint bleed) from the median age of 11.4 months, 90% via a central venous access device. The initial product was rFVIII in 63% and pd-FVIII in 37%, moreover in 24% pd-FVIII was switched to rFVIII concentrate during the 75 EDs. Non-transient inhibitors developed in 9/51 (17.6%; 13.7% high titre) children with primary and in 4/11 (36.4%; 27.3% high titre) patients with secondary prophylaxis (P = 0.24). Overall, 74% had a high-risk genotype similarly distributed among the prophylaxis groups. The history of a major bleed enhanced ID (aHR, 4.0; 95% CI, 1.2-13.7), whereas FVIII treatment intensity or source and early implantation of ports did not increase ID risk. CONCLUSION: The cumulative incidence of ID was low notwithstanding prevalent high-risk mutations. Despite patient-related risk factors, our management involving early intensive primary prophylaxis via ports helps to prevent bleeds and lower the incidence of inhibitors.
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Anticorpos Neutralizantes/sangue , Coagulantes/uso terapêutico , Fator VIII/uso terapêutico , Hemofilia A/tratamento farmacológico , Pré-Escolar , Fator VIII/genética , Finlândia , Genótipo , Hemofilia A/genética , Hemofilia A/patologia , Hemorragia , Humanos , Lactente , Recém-Nascido , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Topological defects play important roles throughout nature, appearing in contexts as diverse as cosmology, particle physics, superfluidity, liquid crystals, and metallurgy. Point defects can arise naturally as magnetic monopoles resulting from symmetry breaking in grand unified theories. We devised an experiment to create and detect quantum mechanical analogs of such monopoles in a spin-1 Bose-Einstein condensate. The defects, which were stable on the time scale of our experiments, were identified from spin-resolved images of the condensate density profile that exhibit a characteristic dependence on the choice of quantization axis. Our observations lay the foundation for experimental studies of the dynamics and stability of topological point defects in quantum systems.
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Children with haemophilia require venous access for regular infusion of coagulation factors. A central venous access device (CVAD) ensures long-term access but associates with infectious and non-infectious complications with proposed risk factors of young age at initial CVAD implantation and presence of an inhibitor. Our aim was to evaluate the incidence and risk factors for complications associated with CVAD usage in a retrospective nationwide multicentre study in five Finnish Paediatric Haemophilia Treatment Centers. Our study investigated 106 CVADs in 58 patients with 137 971 CVAD days. The median access survival was 1159 CVAD days, and most often a malfunction led to CVAD removal after a long survival (median of 1640 CVAD days). We detected a very low bloodstream infection rate (0.12/1000 CVAD days). The presence of neutralizing inhibitor was a significant risk factor for infection. Heparin vs. saline flushing did not influence the CVAD outcome. We detected a lower infection rate than previously reported, although 90% of the patients were very young (<2 years) at first insertion (median age = 1.02 year). Port access was frequent after initial implantation: six patients (10%) used the port daily for immune tolerance induction therapy and 74% at least twice weekly for prophylaxis. Young age did not increase the risk of infections, as 59% of the CVAD-related infections were recorded in children over 6 years of age. Our national experience confirms the safety of prophylactic factor concentrate administration via ports even in very young children.
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Cateterismo Venoso Central/efeitos adversos , Hemofilia A/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Finlândia , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
We extend the quantum jump method to nearly adiabatically driven open quantum systems in a way that allows for an accurate account of the external driving in the system-environment interaction. Using this framework, we construct the corresponding trajectory-dependent work performed on the system and derive the integral fluctuation theorem and the Jarzynski equality for nearly adiabatic driving. We show that such identities hold as long as the stochastic dynamics and work variable are consistently defined. We numerically study the emerging work statistics for a two-level quantum system and find that the conventional diabatic approximation is unable to capture some prominent features arising from driving, such as the continuity of the probability density of work. Our results reveal the necessity of using accurate expressions for the drive-dressed heat exchange in future experiments probing jump time distributions.
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As quantum systems become more experimentally accessible, we are forced to reconsider the notions of control and work to fully account for quantum effects. To this end, we identify the work injected into a quantum system during a general quantum-mechanical driving protocol and quantify the relevant heat flows. The known results that are applicable in the limit of a classical drive are shown to emerge from our equations as a special case. Using the established framework, we show that the Bochkov-Kuzovlev identity for the exclusive work distribution is modified in a nontrivial way by the accumulation of system-drive correlations resulting from quantum back action. Our results accentuate the conceptual and discernible differences between a fully quantum-mechanical and classical driving protocols of quantum systems.
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Magnetic monopoles--particles that behave as isolated north or south magnetic poles--have been the subject of speculation since the first detailed observations of magnetism several hundred years ago. Numerous theoretical investigations and hitherto unsuccessful experimental searches have followed Dirac's 1931 development of a theory of monopoles consistent with both quantum mechanics and the gauge invariance of the electromagnetic field. The existence of even a single Dirac magnetic monopole would have far-reaching physical consequences, most famously explaining the quantization of electric charge. Although analogues of magnetic monopoles have been found in exotic spin ices and other systems, there has been no direct experimental observation of Dirac monopoles within a medium described by a quantum field, such as superfluid helium-3 (refs 10-13). Here we demonstrate the controlled creation of Dirac monopoles in the synthetic magnetic field produced by a spinor Bose-Einstein condensate. Monopoles are identified, in both experiments and matching numerical simulations, at the termini of vortex lines within the condensate. By directly imaging such a vortex line, the presence of a monopole may be discerned from the experimental data alone. These real-space images provide conclusive and long-awaited experimental evidence of the existence of Dirac monopoles. Our result provides an unprecedented opportunity to observe and manipulate these quantum mechanical entities in a controlled environment.
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We introduce a setup which realises a tunable engineered environment for experiments in circuit quantum electrodynamics. We illustrate this concept with the specific example of a quantum bit, qubit, in a high-quality-factor cavity which is capacitively coupled to another cavity including a resistor. The temperature of the resistor, which acts as the dissipative environment, can be controlled in a well defined manner in order to provide a hot or cold environment for the qubit, as desired. Furthermore, introducing superconducting quantum interference devices (SQUIDs) into the cavity containing the resistor, provides control of the coupling strength between this artificial environment and the qubit. We demonstrate that our scheme allows us to couple strongly to the environment enabling rapid initialization of the system, and by subsequent tuning of the magnetic flux of the SQUIDs we may greatly reduce the resistor-qubit coupling, allowing the qubit to evolve unhindered.
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Recent progress on micro- and nanometer-scale manipulation has opened the possibility to probe systems small enough that thermal fluctuations of energy and coordinate variables can be significant compared with their mean behavior. We present an experimental study of nonequilibrium thermodynamics in a classical two-state system, namely, a metallic single-electron box. We have measured with high statistical accuracy the distribution of dissipated energy as single electrons are transferred between the box electrodes. The obtained distributions obey Jarzynski and Crooks fluctuation relations. A comprehensive microscopic theory exists for the system, enabling the experimental distributions to be reproduced without fitting parameters.
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We show that the effect of a high-temperature environment in current transport through a normal metal-insulator-superconductor tunnel junction can be described by an effective density of states in the superconductor. In the limit of a resistive low-Ohmic environment, this density of states reduces into the well-known Dynes form. Our theoretical result is supported by experiments in engineered environments. We apply our findings to improve the performance of a single-electron turnstile, a potential candidate for a metrological current source.
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One of the challenges of adiabatic control theory is the proper inclusion of the effects of dissipation. Here we study the adiabatic dynamics of an open two-level quantum system deriving a generalized master equation to consistently account for the combined action of the driving and dissipation. We demonstrate that in the zero-temperature limit the ground state dynamics is not affected by environment. As an example, we apply our theory to Cooper pair pumping, which demonstrates the robustness of ground state adiabatic evolution.