Swift chiral quantum walks

A continuous-time quantum walk (CTQW) is sedentary if the return probability in the starting vertex is close to one at all times. Recent results imply that, when starting from a maximal degree vertex, the CTQW dynamics generated by the Laplacian and adjacency matrices are typically sedentary. In this paper, we show that the addition of appropriate complex phases to the edges of the graph, defining a chiral CTQW, can cure sedentarity and lead to swift chiral quantum walks of the adjacency type, which bring the returning probability to zero in the shortest time possible. We also provide a no-go theorem for swift chiral CTQWs of the Laplacian type. Our results provide one of the first, general characterization of tasks that can and cannot be achieved with chiral CTQWs.Comment: 20 pages, 2 figure

Quantum routing of information using chiral quantum walks

We address routing of classical and quantum information over quantum network, and show how to exploit chirality to achieve nearly optimal and robust transport. In particular, we prove how continuous time chiral quantum walks over a minimal graph may be used to model directional transfer and routing of information over a network. At first, we show how classical information, encoded onto an excitation localized at one vertex of a simple graph, may be sent to any other chosen location with nearly unit fidelity by tuning a single phase. Then, we prove that high-fidelity transport is also possible for coherent superpositions of states, i.e. for routing of quantum information. Furthermore, we show that by tuning the phase parameter one obtains universal quantum routing, i.e. indipendent on the input state. In our scheme, chirality is governed by a single phase, and the routing probability is robust against fluctuations of this parameter. Finally, we address characterization of quantum routers and show how to exploit the self energies of the graph to achieve high precision in estimating the phase parameter.Comment: This paper has been submitted to the Jonathan P. Dowling Memorial Special Issue of AVS QUANTUM SCIENCE (https://publishing.aip.org/publications/journals/special-topics/aqs/

Model-Driven Development of Distributed Ledger Applications

Distributed Ledger Technology (DLT) is one of the most durable results of virtual currencies, which goes beyond the financial sector and impacts business applications in general. Developers can empower their solutions with DLT capabilities to attain such benefits as decentralization, transparency, non-repudiability of actions and security and immutability of data assets, to the price of integrating a distributed ledger framework into their software architecture. Model-Driven Development (MDD) is the discipline that advocates the use of abstract models and of code generation to reduce the application development and integration effort by delegating repetitive coding to an automated model-to-code transformation engine. In this paper, we explore the suitability of MDD to support the development of hybrid applications that integrate centralized database and distributed ledger architectures and describe a prototypical tool capable of generating the implementation artefacts starting from a high-level model of the application and its architecture.This preprint has not undergone peer review (when applicable) or any post-submission improvements or corrections. The Version of Record of this contribution is published in Lecture Notes in Computer Science, and a link to the published version will be added when available

The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration:Insights from the IMPROVE Study

The impact of cholesteryl ester transfer protein (CETP) on atherosclerosis is highly debated. This study aimed to investigate the associations between plasma CETP or CETP genotypes and carotid intima-media thickness (cIMT) and the influence of high-density lipoprotein cholesterol (HDL-C) on these associations. Plasma CETP and HDL-C concentrations were measured in 552 subjects free of any pharmacological treatment from the IMPROVE cohort, which includes 3711 European subjects at high cardiovascular risk. CETP single-nucleotide polymorphisms (SNPs) and cIMT measures (cIMT(max); cIMT(mean-max) of bifurcations, common and internal carotids; plaque-free common carotid [PF CC]-IMTmean) were available for the full cohort. In drug-free subjects, plasma CETP correlated with HDL-C levels (r = 0.19, p < 0.0001), but not with cIMT variables. When stratified according to HDL-C quartiles, CETP positively correlated with cIMT(max) and cIMT(mean-max), but not with PF CC-IMTmean, in the top HDL-C quartile only. Positive associations between the CETP concentration and cIMT(max) or cIMT(mean-max) were found in the top HDL-C quartile, whereas HDL-C levels were negatively correlated with cIMT(max) and cIMT(mean-max) when the CETP concentration was below the median (HDL-C x CETP interaction, p = 0.001 and p = 0.003 for cIMT(max) and cIMT(mean-max), respectively). In the full cohort, three CETP SNPs (rs34760410, rs12920974, rs12708968) were positively associated with cIMT(max). rs12444708 exhibited a significant interaction with HDL-C levels in the prediction of cIMT(max). In conclusion, a significant interplay was found between plasma CETP and/or CETP genotype and HDL-C in the prediction of carotid plaque thickness, as indexed by cIMT(max). This suggests that the association of HDL-C with carotid atherosclerosis is CETP-dependent

Sex-specific predictors of PCSK9 levels in a European population:The IMPROVE study

Background and aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of low-density lipoprotein cholesterol plasma levels and circulating PCSK9, which differs between genders. PCSK9 represents a valid pharmacological target for preventing cardiovascular (CV) events. We aimed to investigate sex-related associations between PCSK9 plasma levels and biochemical and anthropomorphic factors, and familial and personal morbidities, in a large European cohort (n=3,673) of men (47.9%) and women (52.1%). Methods: Individuals (aged 54 to 79 years) free of CV diseases were enrolled in 7 centers of five European countries: Finland, France, Italy, the Netherlands, and Sweden. PCSK9 plasma levels were measured by ELISA. Results: PCSK9 was higher in women than in men. Multiple linear regression analysis showed that latitude, sex, and treatments with statins and fibrates were the strongest predictors of PCSK9 in the whole group. These variables, together with triglycerides and high-density lipoprotein cholesterol, were also associated with PCSK9 in men or women. Mean corpuscular hemoglobin concentration and pack-years were PCSK9 independent predictors in women, whereas hypercholesterolemia and physical activity were independent predictors in men. The associations between PCSK9 and latitude, uric acid, diabetes, hypercholesterolemia and physical activity were significantly different in men and women (pinteraction &lt;0.05 for all). Conclusions: Besides confirming the association with lipids in the whole group, our study revealed previously unknown differences in PCSK9 predictors in men and women. These might be taken into account when defining individual risk for CV events and/or for refining PCSK9 lowering treatments

Synthesis and Superpotent Anticancer Activity of Tubulysins Carrying Non-hydrolysable N-Substituents on Tubuvaline

We thank Regione Autonoma della Sardegna RAS (Italy) for economic support by covering in part the costs of this research. I.U. acknowledges RAS for his fellowship (for grant numbers see the Supporting Information)Peer reviewedPostprin

miR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators

BACKGROUND: Targeted therapy with BRAF and MEK inhibitors has improved the survival of patients with BRAF-mutated metastatic melanoma, but most patients relapse upon the onset of drug resistance induced by mechanisms including genetic and epigenetic events. Among the epigenetic alterations, microRNA perturbation is associated with the development of kinase inhibitor resistance. Here, we identified and studied the role of miR-146a-5p dysregulation in melanoma drug resistance.METHODS: The miR-146a-5p-regulated NFkB signaling network was identified in drug-resistant cell lines and melanoma tumor samples by expression profiling and knock-in and knock-out studies. A bioinformatic data analysis identified COX2 as a central gene regulated by miR-146a-5p and NFkB. The effects of miR-146a-5p/COX2 manipulation were studied in vitro in cell lines and with 3D cultures of treatment-resistant tumor explants from patients progressing during therapy.RESULTS: miR-146a-5p expression was inversely correlated with drug sensitivity and COX2 expression and was reduced in BRAF and MEK inhibitor-resistant melanoma cells and tissues. Forced miR-146a-5p expression reduced COX2 activity and significantly increased drug sensitivity by hampering prosurvival NFkB signaling, leading to reduced proliferation and enhanced apoptosis. Similar effects were obtained by inhibiting COX2 by celecoxib, a clinically approved COX2 inhibitor.CONCLUSIONS: Deregulation of the miR-146a-5p/COX2 axis occurs in the development of melanoma resistance to targeted drugs in melanoma patients. This finding reveals novel targets for more effective combination treatment. Video Abstract

Determinants of carotid wall echolucency in a cohort of European high cardiovascular risk subjects: A cross-sectional analysis of IMPROVE baseline data

Echolucency, a measure of plaque instability associated with increased cardiovascular risk, can be assessed in both the carotid plaque and the plaque-free common carotid intima–media (IM) complex as a gray-scale median (plaque-GSM and IM-GSM, respectively). The impact of specific vascular risk factors on these two phenotypes remains uncertain, including the nature and extent of their influence. This study aims to seek the determinants of plaque-GSM and IM-GSM. Plaque-GSM and IM-GSM were measured in subjects from the IMPROVE study cohort (aged 54–79, 46% men) recruited in five European countries. Plaque-GSM was measured in subjects who had at least one IMTmax ≥ 1.5 mm (n = 2138), whereas IM-GSM was measured in all subjects included in the study (n = 3188). Multiple regression with internal cross-validation was used to find independent predictors of plaque-GSM and IM-GSM. Plaque-GSM determinants were plaque-size (IMTmax), and diastolic blood pressure. IM-GSM determinants were the thickness of plaque-free common carotid intima–media complex (PF CC-IMTmean), height, systolic blood pressure, waist/hip ratio, treatment with fibrates, mean corpuscular volume, treatment with alpha-2 inhibitors (sartans), educational level, and creatinine. Latitude, and pack-yearscode were determinants of both plaque-GSM and IM-GSM. The overall models explain 12.0% of plaque-GSM variability and 19.7% of IM-GSM variability. A significant correlation (r = 0.51) was found between plaque-GSM and IM-GSM. Our results indicate that IM-GSM is a weighty risk marker alternative to plaque-GSM, offering the advantage of being readily measurable in all subjects, including those in the early phases of atherosclerosis where plaque occurrence is relatively infrequent