A Blockchain-Based Solution for Enabling Log-Based Resolution of Disputes in Multi-party Transactions

We are witnessing an ongoing global trend towards the automation of almost any transaction through the employment of some Internet-based mean. Furthermore, the large spread of cloud computing and the massive emergence of the software as a service (Saas) paradigm have unveiled many opportunities to combine distinct services, provided by different parties, to establish higher level and more advanced services, that can be offered to end users and enterprises. Business-to-business (B2B) integration and third-party authorization (i.e. using standards like OAuth) are examples of processes requiring more parties to interact with each other to deliver some desired functionality. These kinds of interactions mostly consist of transactions and are usually regulated by some agreement which defines the obligations that involved parties have to comply with. In case one of the parties claims a violation of some clause of such agreement, disputes can occur if the party accused of the infraction refuses to recognize its fault. Moreover, in case of auditing, for convenience reasons a party may deny to have taken part in a given transaction, or may forge historical records related to that transaction. Solutions based on a trusted third party (TTP) have drawbacks: high overhead due to the involvement of an additional party, possible fees to pay for each transaction, and the risks stemming from having to blindly trust another party. If it were possible to only base on transaction logs to sort disputes out, then it would be feasible to get rid of any TTP and related shortcomings. In this paper we propose SLAVE, a blockchain-based solution which does not require any TTP. Storing transactions in a public blockchain like Bitcoin’s or Ethereum’s provides strong guarantees on transactions’ integrity, hence they can be actually used as proofs when controversies arise. The solution we propose defines how to embed transaction logs in a public blockchain, so that each involved party can verify the identity of the others while keeping confident the content of transactions

Molecular and functional characterization of the role of the histone methyltransferase SETDB1 in malignant melanoma

Malignant melanoma is the most deadly skin cancer. Clinical studies reported a dramatic increase in the incidence of melanoma over the past few years. A very distinctive feature of melanoma is its high degree of heterogeneity and cellular plasticity. Within the tumor there are different genetically defined subpopulations of melanoma cells, which is one of the reasons for the low efficacy of targeted therapies. Furthermore, most melanomas quickly develop a resistance to these therapies, causing tumor relapse. For all these reasons, gaining an understanding of the molecular and cellular mechanisms driving melanoma progression will be important for developing potent therapeutic approaches. So far, some key regulatory pathways normally activated in melanoma have been well defined, and these pathways are mainly driven by activation of oncogenes like BRAF and NRAS, with a considerable relevance for clinical practice. However, the identification of novel key regulators and pathways is still a challenge and will help to better understand melanoma development and to open up new possibilities to treat therapy resistant tumors. Recent studies and work previously conducted in our laboratory reported that the histone methyltransferase SETDB1 plays a major role in melanoma pathogenesis. It has been observed that SETDB1 expression, which correlates with its amplification state in melanoma, is also associated with melanoma progression. However, the role of SETDB1 and its mode of action in melanoma are still unclear. The aim of this project is to clarify the role of SETDB1 in melanoma, through the identification and functional characterization of SETDB1-mediated molecular mechanisms. Here, I report that SETDB1 expression caused deep changes in melanoma transcriptome resulting in the deregulation of pro- and anti-tumorigenic factors. Specifically, SETDB1 induced THBS1 upregulation and suppressed DCT expression. SETDB1 functions are dependent on its catalytic SET domain. During melanoma progression, SETDB1 promoted important epigenetic alterations such as changing the genomic distribution of H3K9me3 and H3K4me1 marks. These histone 2 modifications impacted the transcription of SETDB1 downstream targets. I could show that melanoma cells were sensitive to treatment with the SETDB1-inhibitor mithramycin A. Mithramycin treatment suppressed SETDB1 expression and tumorigenic properties of melanoma cells. Combinatorial treatment with mithramycin and MAPK inhibitors showed enhanced anti-tumor effects. Taken together, the findings presented here highlight the crucial functional and mechanistic role of SETDB1 in melanoma. SETDB1 could be considered as a potential future target for the treatment of melanoma

Clinical validation of a coronary surgery technique that minimizes aortic manipulation

BACKGROUND: To minimize aortic manipulation and maximize use of arterial conduits are aims of modern coronary surgery. METHODS: From March 2012 to October 2016, 890 consecutive patients with multivessel coronary disease underwent isolated coronary surgery using both internal thoracic arteries (ITAs). In 205 (23%; mean age, 67.6\ub19.2 years), the right ITA was proximally transected and used as free graft, while its in situ stump was elongated with a saphenous vein graft. The new arteriovenous I-conduit was directed to the inferolateral cardiac wall. Operative data and early outcomes of these patients (I-group) were compared with the remaining 685 patients (C-group). Early and late outcomes were compared also in 184 pairs identified with the propensity score-matching. RESULTS: Between I and C-group there was no significant difference on expected operative risk (European System for Cardiac Operative Risk Evaluation II, p=0.28), though diseased ascending aorta (p<0.0001) and critical preoperative state (p=0.027) were more frequent in I-group. Despite higher number of coronary anastomoses (mean, 4\ub10.9 vs. 3.7\ub11, p<0.0001), cardiopulmonary bypass time (minutes) was shorter in I-group both in overall (86.7\ub123.7 vs. 105.7\ub134.2, p<0.0001) and matched series (86.8\ub124.1 vs. 108.8\ub131.9, p<0.0001). In-hospital mortality (1% vs. 1.9%, p=0.54) and the rates of postoperative complications were similar. During the follow-up period, in matched patients, no intergroup difference was found about the non-parametric estimates of freedom from all-cause death (p=0.39) and major adverse cardiac and cerebrovascular events (p=0.44). CONCLUSIONS: Surgery using this arteriovenous I-conduit is safe, minimizes aortic manipulation, makes shorter cardiopulmonary bypass time, and aids complete revascularization

Diffuse infiltrating tumour with the molecular profile of an atypical teratoid rhabdoid tumour (AT/RT SHH-1B) in an adult patient

We describe a 46-year-old patient with an IDH-wildtype diffusely infiltrating atypical teratoid/rhabdoid tumour (AT/RT), SHH-1B molecular subtype. The unusual histology and subsequent diagnosis in an adult patient will be discussed.</p

The STRIP instrument of the Large Scale Polarization Explorer: microwave eyes to map the Galactic polarized foregrounds

In this paper we discuss the latest developments of the STRIP instrument of the "Large Scale Polarization Explorer" (LSPE) experiment. LSPE is a novel project that combines ground-based (STRIP) and balloon-borne (SWIPE) polarization measurements of the microwave sky on large angular scales to attempt a detection of the "B-modes" of the Cosmic Microwave Background polarization. STRIP will observe approximately 25% of the Northern sky from the "Observatorio del Teide" in Tenerife, using an array of forty-nine coherent polarimeters at 43 GHz, coupled to a 1.5 m fully rotating crossed-Dragone telescope. A second frequency channel with six-elements at 95 GHz will be exploited as an atmospheric monitor. At present, most of the hardware of the STRIP instrument has been developed and tested at sub-system level. System-level characterization, starting in July 2018, will lead STRIP to be shipped and installed at the observation site within the end of the year. The on-site verification and calibration of the whole instrument will prepare STRIP for a 2-years campaign for the observation of the CMB polarization.Comment: 17 pages, 15 figures, proceedings of the SPIE Astronomical Telescopes + Instrumentation conference "Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy IX", on June 15th, 2018, Austin (TX

QUBIC: Exploring the Primordial Universe with the Q&U Bolometric Interferometer

In this paper, we describe QUBIC, an experiment that will observe the polarized microwave sky with a novel approach, which combines the sensitivity of state-of-the-art bolometric detectors with the systematic effects control typical of interferometers. QUBIC’s unique features are the so-called “self-calibration”, a technique that allows us to clean the measured data from instrumental effects, and its spectral imaging power, i.e., the ability to separate the signal into various sub-bands within each frequency band. QUBIC will observe the sky in two main frequency bands: 150 GHz and 220 GHz. A technological demonstrator is currently under testing and will be deployed in Argentina during 2019, while the final instrument is expected to be installed during 2020.Fil: Mennella, Aniello. University of Milan; ItaliaFil: Barbaràn, Gustavo. Comisión Nacional de Energía Atómica; ArgentinaFil: Bonaparte, Juan. Comisión Nacional de Energía Atómica; ArgentinaFil: Di Donato, Andrés Leonardo. Comisión Nacional de Energía Atómica; ArgentinaFil: Etchegoyen, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Fasciszewski, Adrián. Comisión Nacional de Energía Atómica; ArgentinaFil: Gamboa Lerena, Martin Miguel. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; ArgentinaFil: Garcia, Beatriz Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Gómez Berisso, Mariano. Centro Atómico Bariloche. Instituto Balseiro; ArgentinaFil: González. Manuel. Centro Atómico Bariloche. Instituto Balseiro; ArgentinaFil: Luterstein, Raùl Horacio. Comisión Nacional de Energía Atómica; ArgentinaFil: Harari, Diego Dario. Centro Atómico Bariloche. Instituto Balseiro; ArgentinaFil: Kristukat, Christian. Universidad Nacional de San Martín; ArgentinaFil: Medina, Maria Clementina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Mundo, Luis Mariano. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; ArgentinaFil: Pastoriza, Hernan. Centro Atómico Bariloche. Instituto Balseiro; ArgentinaFil: Ringegni, Pablo. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; ArgentinaFil: Romero, Gustavo Esteban. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Scóccola, Claudia G.. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; ArgentinaFil: Suarez, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: The Qubic Collaboration. No especifíca;7th International Conference on New frontiers in PhysicsCretaGreciaCenter of the Orthodox Academy of Cret

A Distinct Pattern of Circulating Amino Acids Characterizes Older Persons with Physical Frailty and Sarcopenia: Results from the BIOSPHERE Study

Physical frailty and sarcopenia (PF&amp;S) are hallmarks of aging that share a common pathogenic background. Perturbations in protein/amino acid metabolism may play a role in the development of PF&amp;S. In this initial report, 68 community-dwellers aged 70 years and older, 38 with PF&amp;S and 30 non-sarcopenic, non-frail controls (nonPF&amp;S), were enrolled as part as the "BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons" (BIOSPHERE) study. A panel of 37 serum amino acids and derivatives was assayed by UPLC-MS. Partial Least Squares\u207bDiscriminant Analysis (PLS-DA) was used to characterize the amino acid profile of PF&amp;S. The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classification was 76.6 \ub1 3.9% (75.1 \ub1 4.6% for enrollees with PF&amp;S; 78.5 \ub1 6.0% for nonPF&amp;S). Older adults with PF&amp;S were characterized by higher levels of asparagine, aspartic acid, citrulline, ethanolamine, glutamic acid, sarcosine, and taurine. The profile of nonPF&amp;S participants was defined by higher concentrations of \u3b1-aminobutyric acid and methionine. Distinct profiles of circulating amino acids and derivatives characterize older people with PF&amp;S. The dissection of these patterns may provide novel insights into the role played by protein/amino acid perturbations in the disabling cascade and possible new targets for interventions

ATRT–SHH comprises three molecular subgroups with characteristic clinical and histopathological features and prognostic significance

Atypical teratoid/rhabdoid tumor (ATRT) is an aggressive central nervous system tumor characterized by loss of SMARCB1/INI1 protein expression and comprises three distinct molecular groups, ATRT–TYR, ATRT–MYC and ATRT–SHH. ATRT–SHH represents the largest molecular group and is heterogeneous with regard to age, tumor location and epigenetic profile. We, therefore, aimed to investigate if heterogeneity within ATRT–SHH might also have biological and clinical importance. Consensus clustering of DNA methylation profiles and confirmatory t-SNE analysis of 65 ATRT–SHH yielded three robust molecular subgroups, i.e., SHH-1A, SHH-1B and SHH-2. These subgroups differed by median age of onset (SHH-1A: 18 months, SHH-1B: 107 months, SHH-2: 13 months) and tumor location (SHH-1A: 88% supratentorial; SHH-1B: 85% supratentorial; SHH-2: 93% infratentorial, often extending to the pineal region). Subgroups showed comparable SMARCB1 mutational profiles, but pathogenic/likely pathogenic SMARCB1 germline variants were over-represented in SHH-2 (63%) as compared to SHH-1A (20%) and SHH-1B (0%). Protein expression of proneural marker ASCL1 (enriched in SHH-1B) and glial markers OLIG2 and GFAP (absent in SHH-2) as well as global mRNA expression patterns differed, but all subgroups were characterized by overexpression of SHH as well as Notch pathway members. In a Drosophila model, knockdown of Snr1 (the fly homologue of SMARCB1) in hedgehog activated cells not only altered hedgehog signaling, but also caused aberrant Notch signaling and formation of tumor-like structures. Finally, on survival analysis, molecular subgroup and age of onset (but not ASCL1 staining status) were independently associated with overall survival, older patients (> 3 years) harboring SHH-1B experiencing relatively favorable outcome. In conclusion, ATRT–SHH comprises three subgroups characterized by SHH and Notch pathway activation, but divergent molecular and clinical features. Our data suggest that molecular subgrouping of ATRT–SHH has prognostic relevance and might aid to stratify patients within future clinical trials. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00401-022-02424-5

QUBIC: The Q&U Bolometric Interferometer for Cosmology - A novel way to look at the polarized Cosmic Microwave Background

In this paper we describe QUBIC, an experiment that takes up the challenge posed by the detection of primordial gravitational waves with a novel approach, that combines the sensitivity of state-of-the art bolometric detectors with the systematic effects control typical of interferometers. The so-called "self-calibration" is a technique deeply rooted in the interferometric nature of the instrument and allows us to clean the measured data from instrumental effects. The first module of QUBIC is a dual band instrument (150 GHz and 220 GHz) that will be deployed in Argentina during the Fall 2018.Fil: Mennella, Aniello. University of Milan; ItaliaFil: Ade, P. A. R.. Cardiff University; Reino UnidoFil: Aumont, J.. Institut d'Astrophysique Spatiale; FranciaFil: Banfie, S.. Istituto Nazionale Di Fisica Nucleare; ItaliaFil: Battaglia, P.. Università degli Studi di Trieste; ItaliaFil: Battistelli, E. S.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Baùe, F.. Istituto Nazionale Di Fisica Nucleare; ItaliaFil: Buzi, D.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Columbro, F.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Bélie, B.. Institute of Fundamental Electronics; FranciaFil: Bennett, D.. Maynooth University; IrlandaFil: Bergé, L.. Centre de Sciences Nucléaires et de Sciences de la Matière; FranciaFil: Bernard, J. Ph.. Institut de Recherche en Astrophysique et Planétologie; FranciaFil: Bersanelli, M.. University of Milan; ItaliaFil: Bigot Sazy, M. A.. APC; FranciaFil: Bleurvacq, N.. APC; FranciaFil: Bordier, G.. APC; FranciaFil: Brossard, J.. APC; FranciaFil: Bunn, E. F.. Richmond University; Estados UnidosFil: Burke, D. P.. Maynooth University; IrlandaFil: Buzi, D.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Buzzelli, A.. Universita Tor Vergata; ItaliaFil: Cammilleri, D.. APC; FranciaFil: Cavaliere, F.. University of Milan; ItaliaFil: Chanial, P.. APC; FranciaFil: Etchegoyen, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Harari, Diego Dario. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Medina, Maria Clementina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Romero, Gustavo Esteban. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Suarez, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaThe European Physical Society Conference on High Energy PhysicsVeneciaItaliaEuropean Physical Societ

Management of the corpse with suspect, probable or confirmed COVID-19 respiratory infection \u2013 Italian interim recommendations for personnel potentially exposed to material from corpses, including body fluids, in morgue structures and during autopsy practice.

non disponibil