1,733 research outputs found
Optimizing quantum error correction for superconducting qubit processors
No full textThe theory of quantum mechanics describes many phenomena that may initially seem to be counter-intuitive and, in some cases, impossible, given the understanding of classical mechanics that most of us are more intimately familiar with. Following its initial introduction, there was a great deal of debate among scientists regarding the predictions made by this theory. The strange nature of quantum mechanics has led to many memorable quotes and the use of “spooky” to describe some of these predictions. Since its initial introduction, quantum mechanics has been rigorously tested and has proven to be quite a successful theory. Quantum mechanics has found many different applications and has led to the existence of devices and technologies we use daily. Another potential application of quantum mechanics is quantum computation, which Richard Feynman first put forward as an idea in 1982. Quantum computers have the potential to solve specific problems that can be infeasible for even the most powerful (classical) supercomputers and have potential applications in many different areas, such as quantum chemistry, cryptography, and optimization. However, performing a quantum computation is challenging and requires overcoming the inherent fragility of quantum systems. Storing information in a quantum system requires it to be well isolated from the environment to avoid any unwanted interactions that can corrupt the stored data. Unfortunately, at the same time, we need the ability to control this system, make it interact with other such systems, and ultimately measure it for us to perform an actual computation. This is a universal issue and all of the systems we have so far developed to be used as quantum bits (qubits) have been plagued by noise. Each operation applied to the qubit or even the act of leaving the qubit idling for some time generally leads to an error with a non-negligible probability. The impact of this noise has so far prevented quantum computers from performing any practical computation. While substantial efforts have been made to reduce these physical error rates over the past several years, we are still far from the universal fault-tolerant quantum computers we ultimately strive for. Fortunately, quantum error correction can help us reach the low error rates necessary for quantum computers to realize their potential applications in the future. This can be achieved by storing the quantum information in a logical qubit instead of a noisy physical one. When using a stabilizer code, which will be the focus of this dissertation, this logical information is distributed over many (noisy) physical qubits, referred to as data qubits. Another set of qubits, the so-called ancilla qubits, is used to perform indirect parity measurements, which do not destroy the stored information but give some information about whether an error has occurred. We then try to interpret this information to identify what errors have happened and correct them, which is done by a classical algorithm referred to as the decoder. Increasing the number of physical qubits used to encode the logical qubits allows more physical errors to be detected and corrected. The number of correctable errors is captured by the distance of the code, defined as the minimum number of physical single-qubit errors that constitute a logical error. One of the critical properties of error correction is the ability to reduce the logical error rate by increasing the code distance, which requires the physical error rates to be below some threshold value. The valiant experimental effort over the years has led to several recent experiments that implement various error-correcting codes and demonstrate the reduction of the error rates promised by error correction. In particular, these experiments (and the experiments leading up to them) identified several noise sources that had not been explored in sufficient detail and could significantly impact the logical performance of the code. In this dissertation, we explore the impact of the noise encountered in transmon-qubit devices on the performance of error-correcting codes, namely the surface code. Transmon qubits are, in practice, multi-level systems, and only the lowest two energy levels are used for computation. Unfortunately, they are also weakly anharmonic, leading to the applied operations having some probability of exciting the qubit outside of this computational subspace, referred to as a leakage error. We explore the impact of leakage in both simulations and experiments and develop schemes to mitigate it. We also consider other approaches to improve the logical performance or to reduce unwanted interactions. In Chapter 2, we develop a realistic model of leakage induced by the two-qubit gates between flux-tunable transmon qubits. We show that leaked qubits effectively spread errors on their neighboring qubits, which are then detected by the parity measurements. We show that a Hidden Markov model can detect the increased error rate due to leakage. This enables us to post-select out runs during which any qubit has leaked to restore the code performance. Unfortunately, post-selection is ultimately not scalable. Instead, it is desirable to have operations that return leaked qubits to the computational subspace. These operations are called leakage-reduction units and convert leakage into a regular error. In Chapter 3, we propose a leakage-reduction scheme, which does not require any overhead in the time needed to perform the parity measurements or an overhead in the quantum hardware. For data qubits, we propose an operation that transfers the leakage to a dedicated readout resonator, where it can quickly decay. This operation is designed to not disturb the computational states, allowing it to be applied unconditionally. For the ancilla qubit, we use the fact that measurements can determine if a qubit is in the leaked state. We then apply a conditional operation to return the qubit to the computational subspace whenever it is measured to be leaked. Using detailed density-matrix simulation, we show that this scheme can be easily implemented to remove qubit leakage from the system, mitigating its impact on the logical performance of the code. In Chapter 4, we realize the data-qubit leakage reduction unit in an experiment and show it can also be used to remove ancilla-qubit leakage, removing the need for fast conditional operations and readout that distinguishes the leaked states. We show that these operations can remove most of the leaked population in about a hundred nanoseconds while having a negligible impact on the computational subspace. We also demonstrate that these operations decrease the number of observed errors by a two-qubit parity check, showing that the effect of leakage can be mitigated. Chapter 5 considers an architecture employing two types of superconducting qubits, the transmon qubit and the fluxonium qubit. These qubits have very different frequencies, making it unclear whether these qubits can even interact with each other in the first place. We show that the interactions with the higher-excited states can be utilized to perform operations between them, and we propose two types of gates. In practice, qubit frequencies are targeted with only a certain precision in fabrication. In certain cases, this can lead to unwanted interaction between qubits that increase the physical error rates, referred to as frequency collisions. We show that the large detuning between these qubits reduces the frequency of frequency collision, thereby increasing the expected fabrication yield. In Chapter 6, we realize a distance-two surface code experiment and perform repeated parity measurements to detect and post-select errors, given that it’s impossible to correct them when using such a small code. We implement a suite of logical operations for this code, including initialization, measurement, and several single-qubit gates. In the context of error detection, a logical operation is said to be fault-tolerant if the errors produced by each operation are detectable. We show that fault-tolerant variants of operations perform better than non-fault-tolerant ones. We also characterize the impact of various noise sources on the code performance. In Chapter 7, we look at another small-distance code, in this case, the distance-seven repetition code. We show that increasing the distance weakly suppresses the logical error rate of the code. We investigate the limiting factors behind the observed logical performance by analyzing the correlation between the observed parity measurements and performing simulations using noise models parameterized by the measured physical error rates. Chapter 8 considers a decoder that can perform the error inference more accurately. In particular, we implement a neural network decoder and investigate how it performs on experimental data from surface code experiments. We show that the accuracy of this decoder approaches what can be achieved by an optimal and computationally inefficient tensor network decoder. Transmon measurement produces analog outcomes. These are then typically converted to binary ones, leading to some information loss. We show how a neural network can also use this analog information to improve the achieved logical performance further. We have investigated the impact of non-conventional errors in simulation and in several experiments, demonstrating the importance of characterizing and mitigating these errors. We expect the methods introduced in this dissertation to lead to lower logical error rates. In the short term, this can aid in demonstrations of the usefulness of error correction. In the long term, addressing such errors is important to ensure the ability to suppress logical error rates to sufficiently low levels. We finish this dissertation with a brief conclusion of each chapter. We also outline several potential challenges that can impact future error-correction experiments, namely how to reduce the larger qubit overhead needed for fault-tolerant computation and several error sources that might become a limiting factor for future error-correction experiments.QCD/Terhal Grou
Benzothiadiazole derivatives endowed with STAT3 inhibition
No full textBENZOTHIADIAZOLE DERIVATIVES ENDOWED WITH STAT3
INHIBITION
Arianna Gelain (1), Matteo Mori (1), Ettore Gilardoni (1), Luca Regazzoni (1), Alessandro Pedretti (1),
Diego Colombo (2), Gary Parkinson (3), Akira Asai (4), Fiorella Meneghetti (1), Stefania Villa (1)
1) Department of Pharmaceutical Sciences, University of Milan, via L. Mangiagalli 25, 20133 Milan, Italy
2) Department of Medical Biotechnology and Translational Medicine, University of Milan, via C. Saldini 50, 20133 Milan,
Italy
3) Department of Pharmaceutical and Biological Chemistry – UCL School of Pharmacy, University College London, 29/39
Brunswick Square, WC1N 1AX London, United Kingdom
4) Center for Drug Discovery – Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku,
422-8526 Shizuoka, Japan
Signal Transducer and Activator of Transcription 3 (STAT3) is a latent cytoplasmic protein over-expressed in
various cancer cell lines1,2. As a part of our ongoing research focused on compounds showing STAT3 SH2
domain inhibiting activity3,4, by a virtual screening approach, we identified 5,6-dimethyl-1H,3H
-2,1,3-benzothiadiazole-2,2-dioxide (1) as potential inhibitor. Several derivatives were synthesized (Figure 1)
and tested. Since compound 1 exhibited the most interesting activity (IC50 = 15.8 ± 0.6 μM by
AlphaScreen-based assay), we decided to investigate the mechanism of its activity by liquid chromatography,
MS and UV studies, discovering compound 1 unexpected interaction also with cysteine residues5.
Figure 1 . Benzothiadiazole-2,2-dioxide derivatives set
References
1) Darnell, J. Jr Science, 1997, 277, 1630-1635
2) Turkson, J. and Jove R. Oncogene, 2000, 19, 6613-6626
3) Meneghetti, F.; Villa, S.; Masciocchi, D.; Barlocco, D.; Toma, L.; Han, D.C.; Kwon, B.M.; Ogo, N.; Asai, A.; Legnani, L.;
Gelain, A. European J. Org. Chem. 2015, 2015, 4907–4912
4) Porta, F.; Facchetti, G.; Ferri, N.; Gelain, A.; Meneghetti, F.; Villa, S.; Barlocco, D.; Masciocchi, D.; Asai, A.; Miyoshi,
N.; Marchianò, S.; Kwon, B.M.; Jin, Y.; Gandin, V.; Marzano, C.; Rimoldi, Eur. J. Med. Chem. 2017, 131, 196–206
5) Mori, M.; Gilardoni, E.; Regazzoni, L.; Pedretti, A.; Colombo, D.; Parkinson, G.; Asai, A,; Meneghetti, F.; Villa, S.;
Gelain, A., Molecules 2020, 25(15), 3509
Synthesis and evaluation of influenza neuraminidases inhibitors based on a bicyclo[3.1.0]hexane scaffold
No full textInfluenza neuraminidase (NA) is the enzyme that releases influenza virions from infected cells, cleaving the sialic acid receptor on host cells. To date, the most successful drugs derived from targeting NA function are Oseltamivir,1 Zanamivir,2 and Peramivir.3 Structurally, these drugs consist of an unsaturated six- or five-membered ring and distinctive structural features incorporated from the sialic acid-based natural substrates.
Ultimately, these structural differences have led to resistant viral strains, especially in the case of oseltamivir.4 The emergence of resistant seasonal and pandemic influenza strains5 underscores the growing demand for the development of new antiviral drugs with novel structural motifs and/or substitution patterns.
This communication describes a novel class of derivatives based on a fused cyclopropane-cyclopentane scaffold, proposed as mimics of the sialic acid distorted boat conformation that occurs during catalysis by influenza neuraminidases (sialidases). A general synthetic route for these constrained-ring molecules was developed utilizing a photochemical reaction, followed by a Johnson-Corey-Chaykovsky cyclopropanation. Functionalization with the aim of additionally reaching the neuraminidase 150-cavity6 was also exploited. Inhibition assays demonstrated low micromolar inhibition against both group-1 (H5N1) and group-2 (H9N2) influenza neuraminidase subtypes, indicating good affinity for the alpha and beta sialic acid mimics and 150-cavity-targeted derivatives. These results provide validation of the design of a rigid bicyclo [3.1.0] analogue as a close mimic of sialic acid in the neuraminidase active site during catalysis.
1. Kim, C. U.; Lew, W.; Williams, M. A.; Liu, H. T.; Zhang, L. J.; Swaminathan, S.; Bischofberger, N.; Chen, M. S.; Mendel, D. B.; Tai, C. Y.; Laver, W. G.; Stevens, R. C. J. Amer. Chem. Soc. 1997, 119 (4), 681-690.
2. Vonitzstein, M.; Wu, W. Y.; Kok, G. B.; Pegg, M. S.; Dyason, J. C.; Jin, B.; Phan, T. V.; Smythe, M. L.; White, H. F.; Oliver, S. W.; Colman, P. M.; Varghese, J. N.; Ryan, D. M.; Woods, J. M.; Bethell, R. C.; Hotham, V. J.; Cameron, J. M.; Penn, C. R. Nature 1993, 363 (6428), 418-423.
3. Babu, Y. S.; Chand, P.; Bantia, S.; Kotian, P.; Dehghani, A.; El-Kattan, Y.; Lin, T. H.; Hutchison, T. L.; Elliott, A. J.; Parker, C. D.; Ananth, S. L.; Horn, L. L.; Laver, G. W.; Montgomery, J. A. J. Med. Chem. 2000, 43 (19), 3482-3486.
4. Nguyen, H. T.; Nguyen, T.; Mishin, V. P.; Sleeman, K.; Balish, A.; Jones, J.; Creanga, A.; Marjuki, H.; Uyeki, T. M.; Nguyen, D. H.; Nguyen, D. T.; Do, H. T.; Klimov, A. I.; Davis, C. T.; Gubareva, L. V. Emerging Infect. Dis. 2013, 19 (12), 1963-1971.
5. McKimm-Breschkin, J. L. Influenza Other. Respir. Viruses 2013, 7, 25-36.
6. Russell, R. J.; Haire, L. F.; Stevens, D. J.; Collins, P. J.; Lin, Y. P.; Blackburn, G. M.; Hay, A. J.; Gamblin, S. J.; Skehel, J. J. J. Amer. Chem. Soc. 2009, 131 (13), 4702-4709
The impact of brief depressive episodes on the outcome of bipolar disorder and major depressive disorder : a 1-year prospective study
No full textBackground: Brief depressive episodes (BDEs) cause psychosocial impairment and increased risk of suicide, worsening the outcome and long-term course of affective disorders. The aim of this naturalistic observational study was to assess the frequency of BDEs and very brief depressive episodes (VBDEs) and their impact on clinical outcome in a sample of patients with major depressive disorder (MDD) and bipolar disorder (BD).
Method: Seventy patients with a diagnosis of MDD or BD were followed up and monthly visited for a period of 12 months, assessing the eventual occurrence of BDEs and/or VBDEs. Clinical and demographic variables of the total sample and of the groups divided according to the presence of BDEs or VBDEs were collected and compared by one-way ANOVAs. Hamilton Depression Rating Scale 21 items (HDRS), Young Mania Rating Scale (YMRS), Clinical Global Impression (severity of illness) (CGIs) and the Short Form Health Survey (SF-36-item 1) were administered at baseline and logistic regression was performed to evaluate whether baseline scores were predictive of the onset of BDEs or VBDEs.
Results: BDEs (88.6% of the total sample), VBDEs (44.3% of the total sample) and BDEs + VBDEs (40.0% of the total sample) were found to occur frequently across the sample. BDE patients showed more death thoughts during major depressive episodes (chi(2) = 4.14, df = 1, p = 0.04, Phi = 0.24) compared to patients without BDEs. Indeed VBDE patients showed a higher rate of hospitalization (,chi(2) = 5.71, df = 1, p = 0.031, phi = 0.29), a more frequent prescription of a combined treatment (chi(2) -= 13.07, df = 7, p = 0.03, phi = 0.43) and higher scores at SF-36 item 1 (F = 6.65, p = 0.01) compared to patients without VBDEs. Finally, higher SF-36 kern 1 scores were found to be predictive of VBDEs (odds ratio = 2.81, p = 0.03).
Discussion: Major depressives, either unipolar or bipolar, with BDEs or VBDEs showed a worse outcome, represented by a more severe psychopathology and higher rates of hospitalization. VBDEs were predicted by a negative subjective general health perception. Studies with larger samples and longer follow-up are warranted to confirm the results of the present study
Effect of the PNPLA3 I148M polymorphism on the outcome of peg-interferon plus ribavirin treatment in chronic hepatitis C
No full textBackground & Aims : Homozygosity for the Patatin-like phospholipase
domain-containing 3 (PNPLA3) p.I148M polymorphism (p.148M/M) has been associated with steatosis, fibrosis
progression, and hepatocellular carcinoma in chronic hepatitis
C (CHC) patients, but the effect on treatment outcome is still controversial. Aim of this study was to evaluate the effect of p.148M/M on the rate of sustained virological response (SVR) and viral kinetics in CHC patients who underwent standard of
care (SOC) antiviral therapy with peg-interferon and ribavirin,
stratified according to viral genotype (genotype 2 (gen2) vs. others), and severity of fibrosis (Metavir 2). Patients: 602 naïve consecutive patients from two tertiary referral centers in Milan and one in Vienna, for whom DNA samples and liver biopsy were available. Mean age 50.8±12 years, 39% were females, 61% gen1, 17% gen2, 6% gen3, 16% gen4, 30% had advanced fibrosis, 33% were IL28B rs12979860 CC.
Results: p.148M/M was detected in 49 patients (8%), and was associated with advanced fibrosis (21/49, 43% vs. 158/553, 28%; p=0.049), but not with demographic, anthropometric, and virological parameters. The p.148M/M genotype was not significantly associated with SVR in the whole series (25/49, 51% vs. 326/553, 59%; p=0.29), but it was associated with a lower SVR rate in non-gen2 patients with advanced fibrosis (4/18, 22% vs. 64/135, 48%; p=0.047). In these subjects, p.148M/M was also associated with a lower rate of complete early viral response (5/18, 28% vs. 80/135, 59%; p=0.021).
SVR was not influenced by p.148M/M in gen2 patients and in patients without advanced fibrosis. In non-gen2 patients, SVR was independently associated with younger age, absence of
advanced fibrosis, IL28B CC genotype, completion of adequate dose treatment (≥80/80/80%), and p.148M/M (OR 0.70, 95% c.i 0.46-1.0). Conclusions: PNPLA3 genotype seems to represent a negative prognostic factor for antiviral
treatment outcome independently of the effect on fibrosis progression,
but only in a very selected subgroup of difficult-to-cure CHC patients (3% in this series). However, whether it also influences the outcome of triple therapies with direct antiviral agents
needs to be evaluated in future studie
Land Use and Land Cover Change in Kolonnawa Marsh, Colombo, Sri Lanka
No full textKolonnawa Marsh (KM) is one of important urban wetland ecosystem in Colombo, Sri Lanka and plays important roles by providing invaluable ecosystem services. KM belongs to the Colombo marsh complex that consists of Heen marsh, Kotte marsh and Parliament lake which surrounded by highly populated and industrialized sites. Owing to the continuous exploitation, reclamation for home states and industries in recent decades, this urban wetland has experienced significant changes. In order toreveal the dynamic changes of the KM at landscape level, the land cover change (LC) since 2000 to 2021 was investigated, using land use maps of 2000 and 2016 from Survey Department of Sri Lanka and Google earth satellite images in 2021. The analysis was conducted using ArcGIS 10.7. The results reviled that in the KM extent has decreased by 34.66 ha from the year 2000 to 30.09 ha in 2016 (reduction percentage 13.2%), while 30.09 ha in 2016 to 28.62 ha in 2021 (reduction percentage 1.47%). Water covered area, marshy area and area covered with woody perennials have been identified as major habitat types in KM. The ratio between water covered areas into marshy land area was reported as 3:6 in 2000 while 1:2 and 1:4 in 2016 and 2021 respectively. Further to that, 18.47 ha of marshy land area has been converted to area dominated with woody perennial in 2021. Therefore, it can be concluded that extent of the KM is decreasing over the study period while transforming to terrestrial ecosystem. Hence, immediate interventions are needed to preserve this valuable freshwater ecosystem.
Keywords: Urban wetland, Remote sensing, Kolonnawa Marsh, Land cove
Jacques Charles Lemaire, Images de la Terre sainte dans le “Voyage” de Georges Lengherand, dans Un exotisme littéraire médiéval? (Actes du colloque du Centre d’Etudes Médiévales et Dialectales de Lille 3, 6-7 octobre 2006)
No full textL’A. analyse le récit du pèlerinage que Georges Lengherand, bourgmestre de Mons, fit en Terre sainte entre février 1486 et février 1487 (un ms. à Lille, B.M., 145; une copie plus tardive, de 1549, est conservée à la B.M. de Valenciennes, ms. 493); attentif aux détails, parfois sensible à l’exotisme des sites, de la nature, des coutumes, Lengherand a mis par écrit ses souvenirs sur la base de notes personnelles et de documents qu’il s’est procurés, en particulier des guides de voyages composés..
Monitoring biodegradation capacity of organic pollutants in the environment
No full textMicro-organismen zijn in staat om organische verbindingen om te zetten in minder schadelijke stoffen en spelen daarom een belangrijke rol bij het opruimen van milieuvervuiling. Voor beleidsmakers, landgebruikers en landeigenaren is het belangrijk dat er bij milieuverontreiniging goed toezicht wordt gehouden op de biologische afbraakprocessen en dat deze goed worden beheerst. Aangezien microbiële activiteit in het milieu wordt beïnvloed door diverse fysische, geochemische en biologische factoren, is nauwkeurige kennis van het afbraakproces hierbij noodzakelijk. In dit promotieonderzoek wordt de relatie tussen geochemische condities en de biologische afbraakcapaciteit van micro-organismen in het milieu beschreven, inclusief methoden om de activiteit en metabole functies van deze micro-organismen in het milieu te mete
Aa. Vv., Medieval Manuscripts in Transition. Tradition and Creative Recycling
No full textTrois contributions concernent la littérature médiévale. Catherine Bel (Métamorphoses des “Métamorphoses”: le conte de Pyramus et Thisbé dans les manuscrits de l’“Ovide moralisé” en vers, pp. 13-35) analyse l’iconographie de cet épisode dans les manuscrits de Rouen B.M., Arsenal 5069 (qui proviennent tous les deux de l’atelier du Maître de Fauvel: dix illustrations au total), et de Lyon B.M. (deux seules enluminures). Elle montre comment un cycle d’images peut constituer une tradition relativ..
Building Simplification using Offset Curves obtained from the Straight Skeleton
No full textWe propose a conceptual simple algorithm based on offset curves obtained from the straight skeleton to simplify building outlines. We present initial results with some real world data and show that the approach can be used to simplify and amalgamate building outlines. We discuss how this approach can be extended to generate smooth transitions for continuous zoom.Accepted Author ManuscriptOLD Department of GIS Technolog
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