Quantum error correction of a qubit encoded in grid states of an oscillator.

The accuracy of logical operations on quantum bits (qubits) must be improved for quantum computers to outperform classical ones in useful tasks. One method to achieve this is quantum error correction (QEC), which prevents noise in the underlying system from causing logical errors. This approach derives from the reasonable assumption that noise is local, that is, it does not act in a coordinated way on different parts of the physical system. Therefore, if a logical qubit is encoded non-locally, we can-for a limited time-detect and correct noise-induced evolution before it corrupts the encoded information1. In 2001, Gottesman, Kitaev and Preskill (GKP) proposed a hardware-efficient instance of such a non-local qubit: a superposition of position eigenstates that forms grid states of a single oscillator2. However, the implementation of measurements that reveal this noise-induced evolution of the oscillator while preserving the encoded information3-7 has proved to be experimentally challenging, and the only realization reported so far relied on post-selection8,9, which is incompatible with QEC. Here we experimentally prepare square and hexagonal GKP code states through a feedback protocol that incorporates non-destructive measurements that are implemented with a superconducting microwave cavity having the role of the oscillator. We demonstrate QEC of an encoded qubit with suppression of all logical errors, in quantitative agreement with a theoretical estimate based on the measured imperfections of the experiment. Our protocol is applicable to other continuous-variable systems and, in contrast to previous implementations of QEC10-14, can mitigate all logical errors generated by a wide variety of noise processes and facilitate fault-tolerant quantum computation.

To catch and reverse a quantum jump mid-flight.

In quantum physics, measurements can fundamentally yield discrete and random results. Emblematic of this feature is Bohr's 1913 proposal of quantum jumps between two discrete energy levels of an atom1. Experimentally, quantum jumps were first observed in an atomic ion driven by a weak deterministic force while under strong continuous energy measurement2-4. The times at which the discontinuous jump transitions occur are reputed to be fundamentally unpredictable. Despite the non-deterministic character of quantum physics, is it possible to know if a quantum jump is about to occur? Here we answer this question affirmatively: we experimentally demonstrate that the jump from the ground state to an excited state of a superconducting artificial three-level atom can be tracked as it follows a predictable 'flight', by monitoring the population of an auxiliary energy level coupled to the ground state. The experimental results demonstrate that the evolution of each completed jump is continuous, coherent and deterministic. We exploit these features, using real-time monitoring and feedback, to catch and reverse quantum jumps mid-flight-thus deterministically preventing their completion. Our findings, which agree with theoretical predictions essentially without adjustable parameters, support the modern quantum trajectory theory5-9 and should provide new ground for the exploration of real-time intervention techniques in the control of quantum systems, such as the early detection of error syndromes in quantum error correction.

Deterministic Remote Entanglement of Superconducting Circuits through Microwave Two-Photon Transitions.

Large-scale quantum information processing networks will most probably require the entanglement of distant systems that do not interact directly. This can be done by performing entangling gates between standing information carriers, used as memories or local computational resources, and flying ones, acting as quantum buses. We report the deterministic entanglement of two remote transmon qubits by Raman stimulated emission and absorption of a traveling photon wave packet. We achieve a Bell state fidelity of 73%, well explained by losses in the transmission line and decoherence of each qubit.

Low levels of C-peptide have clinical significance for established Type 1 diabetes.

AIM: To determine whether the low C-peptide levels (< 50 pmol/l) produced by the pancreas for decades after onset of Type 1 diabetes have clinical significance. METHODS: We evaluated fasting C-peptide levels, duration of disease and age of onset in a large cross-sectional series (n = 1272) of people with Type 1 diabetes. We then expanded the scope of the study to include the relationship between C-peptide and HbA1c control (n = 1273), as well as diabetic complications (n = 324) and presence of hypoglycaemia (n = 323). The full range of C-peptide levels was also compared with 1,5-Anhydroglucitol, a glucose responsive marker. RESULTS: C-peptide levels declined for decades after diagnosis, and the rate of decline was significantly related to age of onset (P < 0.0001), after adjusting for disease duration. C-peptide levels > 10 pmol/l were associated with protection from complications (e.g. nephropathy, neuropathy, foot ulcers and retinopathy; P = 0.03). Low C-peptide levels were associated with poor metabolic control measured by HbA1c (P < 0.0001). Severe hypoglycaemia was associated with the lowest C-peptide levels compared with mild (P = 0.049) or moderate (P = 0.04) hypoglycaemia. All levels of measurable C-peptide were responsive to acute fluctuations in blood glucose levels as assessed by 1,5-Anhydroglucitol (P < 0.0001). CONCLUSIONS: Low C-peptide levels have clinical significance and appear helpful in characterizing groups at-risk for faster C-peptide decline, complications, poorer metabolic control and severe hypoglycaemia. Low C-peptide levels may be a biomarker for characterizing at-risk patients with Type 1 diabetes.

Gastrointestinal ALκ amyloidosis presenting as protein-losing enteropathy correctly diagnosed by immunohistochemistry using amyloid-type-specific antibodies.

A 54-year-old man presented with protein-losing enteropathy. Biopsies from the stomach, duodenum, ileum and colon showed deposits of amyloid. The bone marrow showed plasmacytosis. After an initial misdiagnosis of AA amyloid, a revised diagnosis of ALκ amyloidosis was made at an expert referral laboratory. Care must be taken in the use of antibodies and proper controls in the performance and interpretation of immunohistochemistry for amyloidosis. A wide panel of amyloid-type-specific antibodies must be used and interpreted in comparative mode to avoid misdiagnosis.

Idiopathic systemic AA-amyloidosis in a skunk (Mephitis mephitis).

This report describes a case of systemic amyloidosis in a captive striped skunk. At necropsy, bilateral alopecia, as well as reno-, hepato-, and splenomegaly were present. Congo red staining and immunohistochemistry revealed depositions of AA-amyloid in different organs. The lack of a predisposing disease is suggestive of idiopathic systemic AA-amyloidosis.

Amyloidogenicity assessment of transthyretin gene variants.

OBJECTIVE: Hereditary transthyretin-mediated amyloidosis is a treatable condition caused by amyloidogenic variants in the transthyretin-gene resulting in severe peripheral neuropathy or cardiomyopathy. Only about a third of over 130 known variants are clearly pathogenic, most are classified as variants of uncertain significance. A clear delineation of these into pathogenic or non-pathogenic is highly desirable but hampered by low frequency and penetrance. We thus sought to characterize their amylogenic potential by an unbiased in vitro approach. METHODS: Thioflavin T and turbidity assays were used to compare the potential of mammalian cell expressed wt-transthyretin and 12 variant proteins (either variants of uncertain significance, benign, pathogenic) to aggregate and produce amyloid fibrils in vitro. As proof of principle, the assays were applied to transthyretin-Ala65Val, a variant that was newly detected in a family with peripheral neuropathy and amyloid deposits in biopsies. In silico analysis was performed to compare the position of the benign and pathogenic variants. RESULTS: Transthyretin-Ala65Val showed a significantly higher amyloidogenic potential than wt-transthyretin, in both turbidity- and Thioflavin T-assays, comparable to known pathogenic variants. The other eight tested variants did not show an increased amyloidogenic potential. In silico structural analysis further confirmed differences between pathogenic and benign variants in position and interactions. INTERPRETATION: We propose a biochemical approach to assess amyloidogenic potential of transthyretin variants. As exemplified by transthyretin-Ala65Val, data of three assays together with histopathology clearly demonstrates its amyloidogenicity.

Intraocular ALλ amyloidoma with plasma cell neoplasia in a cat.

An 11-year-old, neutered male domestic short-hair cat was presented with buphthalmos of the right eye and diagnosed with advanced glaucoma. Sonographic examination revealed an iridial thickening. Neoplasia was suspected and an enucleation was performed. Histopathology of the enucleated eye revealed abundant amyloid deposition predominantly in the anterior uveal tract accompanied by few to moderate numbers of well-differentiated plasma cells. The amyloid deposits were identified by staining with Congo red and showing green birefringence under polarized light. Immunohistochemically, amyloid and plasma cells stained intensely only with anti-ALλ antibody, supporting the amyloid tumor being an immunoglobulin-λ-light chain origin. Additional abnormalities included narrowing of the filtration angle and collapse of the ciliary cleft, and trabecular meshwork. One year post-enucleation, the cat was still healthy without signs of systemic amyloidosis or apparent metastatic disease. This is the first report of a cat with noncutaneous extramedullary plasmacytoma originating in the anterior uveal tract with resulting local amyloid.

Liver transplantation and combined liver-heart transplantation in patients with familial amyloid polyneuropathy: a single-center experience.

Liver transplantation (LT) is the only curative option for patients with familial amyloid polyneuropathy (FAP) at present. Twenty patients with FAP underwent LT between May 1998 and June 2007. Transthyretin mutations included predominantly the Val30Met mutation but also 10 other mutations. Seven patients received a pacemaker prior to LT, and because of impairment of mechanical cardiac function, 4 combined heart-liver transplants were performed, 1 simultaneously and 3 sequentially. The first patient, who underwent simultaneous transplantation, died. Seven patients died after LT, with 5 dying within the first year after transplantation. The causes of death were cardiac complications (4 patients), infections (2 patients), and malnutrition (1 patient). One-year survival was 75.0%, and 5-year survival was 64.2%. Gly47Glu and Leu12Pro mutations showed an aggressive clinical manifestation: 2 patients with the Gly47Glu mutation, the youngest patients of all the non-Val30Met patients, suffered from severe cardiac symptoms leading to death despite LT. Two siblings with the Leu12Pro mutation, who presented only with grand mal seizures, died after LT because of sepsis. In conclusion, the clinical course in patients with FAP is very variable. Cardiac symptoms occurred predominantly in patients with non-Val30Met mutations and prompted combined heart-liver transplantation in 4 patients. Although early LT in Val30Met is indicated in order to halt the typical symptoms of polyneuropathy, additional complications occurring predominantly with other mutations may prevail and lead to life-threatening complications or a fatal outcome. Combined heart-liver transplantation should be considered in patients with restrictive cardiomyopathy.

Nephrotic syndrome due to an amyloidogenic mutation in fibrinogen A alpha chain.

We identified amyloid derived from a mutant fibrinogen A alpha chain associated with one of the hereditary amyloidoses by kidney biopsy. The recognition of molecular and etiologic diversity among amyloidoses has revolutionized the management of systemic amyloidosis and necessitates precision in amyloid typing. Pitfalls and recommendations for the differential diagnosis of renal amyloid and current standards of amyloid typing are briefly discussed. Diagnosis of the amyloidosis type must be based on identification of the chemical composition of the amyloid protein in deposits and not on clinical suspicion, laboratory tests, or genetic testing. A clinical correlation is required to support but not make a diagnosis of amyloid type. If a hereditary form is detected by amyloid protein typing, then molecular studies are indicated. Conversely, in cases in which DNA sequence indicates a mutant amyloid precursor protein, protein analysis of the deposits must provide the definitive evidence. Negative or inconclusive results must be investigated further by a reference laboratory with the capability of applying more sophisticated methods.

[Diagnostic and interventional operations in childhood: anesthesiology management]. / Diagnostische und interventionelle Eingriffe im Kindesalter : Anästhesiologisches Management.

Diagnostic and interventional procedures in children often need to be performed under sedation. This prevents pain and stress in children and provides optimal examination conditions. For complete immobilization and stress shielding the depth of sedation often corresponds with general anesthesia. Therefore, established safety standards need to be observed and a fundamental precondition is implementation by a skilled anesthesiologist who can handle the anesthesiology procedure and its possible complications. Organization, schedule, medication, equipment, monitoring and post-anesthesiology care should be institutionally defined. A professional anesthesiology management of pediatric patients is an important factor to increase the quality of care, patient safety and patient satisfaction.

Upper airway resistance: species-related differences.

In veterinary medicine, upper airway resistance deserves a particular attention in equines athletes and brachycephalic dogs. Due to the anatomical peculiarities of the upper airway and/or pathological conditions, significant alterations of performance and/or well being might occur in horses and dogs. Physiological specificities and pathological changes of the lower respiratory tract deserve a major attention in other species.

[Geometry and function of the dog nose: how does function change when form of the nose is changed?]. / Geometrie und Funktion der Hundenase: Wie ändert sich die Funktion, wenn die Form verändert wird?

Nasal airflow resistance in brachycephalic dogs is significantly elevated compared to normal dogs. LaserAssisted TurbinEctomy (LATE)-surgery as well as xylometazolin were shown to reduce pathologically increased intranasal airway resistance in brachycephalic dogs by approximately 50 %. Impulse oscillometry provides a reliable and sensitive method to examine intranasal stenoses in the canine nose. Acoustic rhinometry allows assessment of changes in cross sectional area and volume of the canine nasal cavity.

Novel isolated cerebral ALlambda amyloid angiopathy with widespread subcortical distribution and leukoencephalopathy due to atypical monoclonal plasma cell proliferation, and terminal systemic gammopathy.

Neuropathologic and biochemical findings in a 34-year-old man whose disease began 2 years before death appearing as chronic progressive encephalitis and culminated in mutism are reported. Cerebrospinal fluid and serum of the patient showed a brain-restricted monoclonal lambda-light chain apparently produced by a small monoclonal immunoglobulin Glambda plasma cell population. In the preterminal stage, there was a systemic monoclonal gammopathy, the source of which could not be identified. At autopsy, there was extensive amyloid deposition in most vessels throughout the cerebral and cerebellar white matter, basal ganglia, and thalamus and diffuse leukoencephalopathy; cerebral and cerebellar cortices, other portions of the CNS, and non-CNS tissues were spared. Partial amino acid sequence analysis demonstrated that the amyloidogenic protein originated from immunoglobulin lambda-light chains which were produced by monoclonal plasma cells. There are 2 similar cases reported in the literature. The distribution of ALlambda deposits in these 3 cases indicates that widespread subcortical vascular amyloidosis with leukoencephalopathy is a novel clinicopathologic entity distinguished from other cerebral diseases with local amyloid light chain deposition, including amyloidoma, leptomeningeal vascular amyloidosis, solitary intracerebral plasmacytoma, primary intracerebral lymphoma with plasmacytic differentiation, and multiple sclerosis with demyelination-associated amyloid deposition.

Serum amyloid A enhances plasminogen activation: implication for a role in colon cancer.

We have recently reported that the acute phase protein serum amyloid A (SAA), is locally and differentially expressed in neoplastic tissues of human colon. In the present study, we demonstrate that SAA enhances the plasminogen activation (PA)-activity of HT-29 colon cancer cell line. Cell-associated PA-activity was measured following the plasminogen-dependent ability of the cells to cleave the chromogenic substrate S-2251. The SAA-enhanced PA-activity was inhibited by anti-SAA antibodies. These antibodies also decreased the basal PA-activity of HT-29 cells and neutralized their cytokines (Interleukin-1beta+Interleukin-6)-enhanced PA-activity. Using specific chromogenic substrates and the fibrin clot-lysis assay, we found that SAA enhances also the PA-activity mediated by purified urokinase- and tissue-type plasminogen activators. Together, the data indicate that SAA enhances plasminogen activation and suggest its possible role in plasmin(ogen)-mediated colon cancer progression.

Significant alterations of serum cytokine levels in patients with Peyronie's disease.

OBJECTIVE: To determine the expression of the cytokines transforming growth factor-beta1 (TGF-beta1), interferon-gamma (IFN-gamma), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in serum from patients with Peyronie's disease (PD) compared to healthy controls. MATERIALS AND METHODS: Ninety-one consecutive PD patients aged 20 - 74 years were included in this study. All patients were diagnosed with symptomatic PD for the first time and had a palpable penile plaque. The patients previously had the disease for 6 - 72 months. None of the patients had a severe infectious disease or known systemic illness. For cytokine analyses, peripheral venous blood samples were obtained before treatment. Fifty healthy male blood donors aged 22 - 64 years served as the control group. TGF-beta1, IFN-gamma, Il-6, and TNF-alpha were analyzed quantitatively with commercial immunoassays. RESULTS: Mean cytokine levels in serum from patients were increased for TGF-beta1 and IFN-gamma compared to healthy controls. The difference for TGF-beta1 was considered statistically significant (p < 0.001). IL-6 was not detectable in PD patients (p < 0.01) and TNF-alpha was decreased (p < 0.0001). CONCLUSION: The significantly elevated serum level of the profibrotic TGF-beta1 cytokine underscores the effect of cytokines in the pathophysiology of PD. The significantly decreased TNF-alpha serum level suggested no acute immunomodulatory process. Therefore, the relevance for therapeutic administration of TNF-alpha should be further investigated. Quantification of TGF-beta1 in serum of PD patients provides a possible diagnostic tool and target for therapy. The data on altered cytokine levels in PD patients also provide a new understanding for etiopathogenesis of PD, which warrants further investigation.

Fault-tolerant detection of a quantum error.

A critical component of any quantum error-correcting scheme is detection of errors by using an ancilla system. However, errors occurring in the ancilla can propagate onto the logical qubit, irreversibly corrupting the encoded information. We demonstrate a fault-tolerant error-detection scheme that suppresses spreading of ancilla errors by a factor of 5, while maintaining the assignment fidelity. The same method is used to prevent propagation of ancilla excitations, increasing the logical qubit dephasing time by an order of magnitude. Our approach is hardware-efficient, as it uses a single multilevel transmon ancilla and a cavity-encoded logical qubit, whose interaction is engineered in situ by using an off-resonant sideband drive. The results demonstrate that hardware-efficient approaches that exploit system-specific error models can yield advances toward fault-tolerant quantum computation.

A CNOT gate between multiphoton qubits encoded in two cavities.

Entangling gates between qubits are a crucial component for performing algorithms in quantum computers. However, any quantum algorithm must ultimately operate on error-protected logical qubits encoded in high-dimensional systems. Typically, logical qubits are encoded in multiple two-level systems, but entangling gates operating on such qubits are highly complex and have not yet been demonstrated. Here we realize a controlled NOT (CNOT) gate between two multiphoton qubits in two microwave cavities. In this approach, we encode a qubit in the high-dimensional space of a single cavity mode, rather than in multiple two-level systems. We couple two such encoded qubits together through a transmon, which is driven by an RF pump to apply the gate within 190 ns. This is two orders of magnitude shorter than the decoherence time of the transmon, enabling a high-fidelity gate operation. These results are an important step towards universal algorithms on error-corrected logical qubits.

Intramyocardial inflammation predicts adverse outcome in patients with cardiac AL amyloidosis.

AIMS: To evaluate the influence of endomyocardial biopsy (EMB)-proven intramyocardial inflammation on mortality in patients with cardiac transthyretin amyloid (ATTR) or amyloid light-chain (AL) amyloidosis. METHODS AND RESULTS: We included 54 consecutive patients (mean age 68.83 ± 9.59 years; 45 men) with EMB-proven cardiac amyloidosis. We followed up patients from first diagnostic biopsy to as long as 36 months (mean 11.5 ± 12 months) and compared their outcome with information on all-cause mortality with or without proof of inflammation on EMB. Intramyocardial inflammation was assessed by quantitative immunohistology. Patients suffering from amyloidosis revealed a significant poor prognosis with proof of intramyocardial inflammation in contrast to those without inflammation (log-rank P = 0.019). Re-grouping of patients indicated AL amyloidosis to have a significant impact on all-cause mortality (log-rank P = 0.012). The detailed subgroup analysis showed that patients suffering from AL amyloidosis with intramyocardial inflammation have a significantly worse prognosis compared with AL amyloidosis without inflammation and ATTR with or without inflammation, respectively (log-rank P = 0.014, contingency Fisher's exact test, P = 0.008). CONCLUSION: Our study reports for the first time a high incidence (48.1%) of intramyocardial inflammation in a series of patients with EMB-proven cardiac amyloidosis and could show that in patients with AL amyloidosis, intramyocardial inflammation correlated significantly with increased mortality. Our data have a direct clinical impact because one can hypothesize that additional immunomodulating/anti-inflammatory treatment regimens in patients with biopsy-proven inflammation of heart muscle tissue could be beneficial for patients suffering from cardiac AL amyloidosis.

Transthyretin valine-94-alanine, a novel variant associated with late-onset systemic amyloidosis with cardiac involvement.

A 63-year-old Caucasian male, diagnosed with dilated cardiomyopathy in 1993, remained clinically stable for several years. In 2003, a marked increase of N-terminal pro-natriuretic peptide serum level (611 ng/ml to 4926 ng/ml) was observed; left ventricular (LV) septum thickness was 10 mm. In addition, sensorimotor polyneuropathy and autonomic dysfunction occurred. Further progression of heart failure occurred despite unchanged systolic LV function. Endomyocardial biopsy in 2006 revealed transthyretin amyloidosis by Congo red and immunohistochemical staining, as well as Val94Ala substitution by transthyretin gene analysis. Cardiac amyloid deposition was quantified by technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy. Mutational search of the relatives (n = 1) was unremarkable. The transthyretin Val94Ala mutation is characterized by sensorimotor polyneuropathy, autonomic dysfunction, and gastrointestinal and cardiac involvement with amyloid. This mutation is an addition to the growing spectrum of transthyretin mutations with late onset of clinical symptoms, but noteworthy because of progressive, finally disabling disease course. Final clinical assessment of severity of cardiac involvement in the present patient is rendered complex by possible concomitant or preceding idiopathic dilated cardiomyopathy.