Role of curcumin in idiopathic pulmonary arterial hypertension treatment: A new therapeutic possibility

The idiopathic pulmonary arterial hypertension is a complex disease that mainly affects pulmonary arterial circulation. This undergoes a remodeling with subsequent reduction of flow in the small pulmonary arteries. Because of this damage an increased vascular resistance gradually develops, and over time it carries out in heart failure. The inflammatory process is a key element in this condition, mediated by various cytokines. The inflammatory signal induces activation of NF-jB, and prompts TGF-b-related signaling pathway. Clinical evolution leads to progressive debilitation, greatly affecting the patient quality of life. The actual therapeutic approaches, are few and expensive, and include systemic drugs such as prostanoids, phosphodiesterase inhibitors and antagonists of endothelin-1 (ERBs). Some researchers have long investigated the anti-inflammatory effects of curcumin. It shows a role for inactivation of NF-jB-mediated inflammation. On the basis of these findings we propose a potential role of curcumin and its pharmacologically fit derivatives for treatment of idiopathic pulmonary arterial hypertension

Interoperable Simulation and Serious Games for creating an Open Cyber Range

The paper proposes an open architecture to support the creation of a synthetic environment devoted to simulate complex scenarios related to the protection of cyber-physical systems. The proposed approach is based on applying the combination of interoperable simulation and serious games to develop a framework where different models, as well as real equipment, could interoperate based on High Level Architecture standard. By this approach, it becomes possible to create a federation reproducing a scenario including multiple physical and cyber layers interacting dynamically and reproducing complex situations. The authors propose an example of specific case study conceptually developed to apply this approach

Surface X-ray Diffraction Study of a Bi-Layer Junction Based on Cu and Cd Sulfides for Photovoltaic Applications

none9noThis study investigates the crystal structure of thin films of chalcogenides, particularly a junction with a p-type (Cu2S) and an n-type (CdS) layer deposited one on top of the other on a Ag(111) substrate, starting from an aqueous solution and by means of electrochemical atomic layer deposition (E-ALD) (the system is denoted by (Cu2S)60/(CdS)60/Ag(111)).mixedTommaso Baroni; Francesco Di Benedetto; Andrea Giaccherini; Enrico Berretti; Francesca Russo; Annalisa Guerri; Massimo Innocenti; Francesco Carlà; Roberto FeliciBaroni, Tommaso; DI BENEDETTO, Francesco; Giaccherini, Andrea; Berretti, Enrico; Russo, Francesca; Guerri, Annalisa; Innocenti, Massimo; Carlà, Francesco; Felici, Robert

Synthesis of Large-Area Crystalline MoS2 by Sputter Deposition and Pulsed Laser Annealing

The wafer-scale synthesis of layered transitional metal dichalcogenides presenting good crystal quality and homogeneous coverage is a challenge for the development of next-generation electronic devices. This work explores a fairly unconventional growth method based on a two-step process consisting in sputter deposition of stochiometric MoS2 on Si/SiO2 substrates followed by nanosecond UV (248 nm) pulsed laser annealing. Large-scale 2H-MoS2 multi-layer films were successfully synthetized in a N2-rich atmosphere thanks to a fine-tuning of the laser annealing parameters by varying the number of laser pulses and their energy density. The identification of the optimal process led to the success in achieving a (002)-oriented nanocrystalline MoS2 film without performing post-sulfurization. It is noteworthy that the spatial and temporal confinement of laser annealing keeps the Si/SiO2 substrate temperature well below the back-end-of-line temperature limit of Si CMOS technology (770 K). The synthesis method described here can speed up the integration of large-area 2D materials with Si-based devices, paving the way for many important applications

Insight into Hypoxia Stemness Control

Recently, the research on stemness and multilineage differentiation mechanisms has greatly increased its value due to the potential therapeutic impact of stem cell-based approaches. Stem cells modulate their self-renewing and differentiation capacities in response to endogenous and/or extrin- sic factors that can control stem cell fate. One key factor controlling stem cell phenotype is oxygen (O2). Several pieces of evidence demonstrated that the complexity of reproducing O2 physiological tensions and gradients in culture is responsible for defective stem cell behavior in vitro and after transplantation. This evidence is still worsened by considering that stem cells are conventionally incubated under non-physiological air O2 tension (21%). Therefore, the study of mechanisms and signaling activated at lower O2 tension, such as those existing under native microenvironments (referred to as hypoxia), represent an effective strategy to define if O2 is essential in preserving naïve stemness potential as well as in modulating their differentiation. Starting from this premise, the goal of the present review is to report the status of the art about the link existing between hypoxia and stemness providing insight into the factors/molecules involved, to design targeted strategies that, recapitulating naïve O2 signals, enable towards the therapeutic use of stem cell for tissue engineering and regenerative medicine

A Survey on Design Methodologies for Accelerating Deep Learning on Heterogeneous Architectures

In recent years, the field of Deep Learning has seen many disruptive and impactful advancements. Given the increasing complexity of deep neural networks, the need for efficient hardware accelerators has become more and more pressing to design heterogeneous HPC platforms. The design of Deep Learning accelerators requires a multidisciplinary approach, combining expertise from several areas, spanning from computer architecture to approximate computing, computational models, and machine learning algorithms. Several methodologies and tools have been proposed to design accelerators for Deep Learning, including hardware-software co-design approaches, high-level synthesis methods, specific customized compilers, and methodologies for design space exploration, modeling, and simulation. These methodologies aim to maximize the exploitable parallelism and minimize data movement to achieve high performance and energy efficiency. This survey provides a holistic review of the most influential design methodologies and EDA tools proposed in recent years to implement Deep Learning accelerators, offering the reader a wide perspective in this rapidly evolving field. In particular, this work complements the previous survey proposed by the same authors in [203], which focuses on Deep Learning hardware accelerators for heterogeneous HPC platforms

The scaffold protein p140Cap limits ERBB2-mediated breast cancer progression interfering with Rac GTPase-controlled circuitries.

The docking protein p140Cap negatively regulates tumour cell features. Its relevance on breast cancer patient survival, as well as its ability to counteract relevant cancer signalling pathways, are not fully understood. Here we report that in patients with ERBB2-amplified breast cancer, a p140Cap-positive status associates with a significantly lower probability of developing a distant event, and a clear difference in survival. p140Cap dampens ERBB2- positive tumour cell progression, impairing tumour onset and growth in the NeuT mouse model, and counteracting epithelial mesenchymal transition, resulting in decreased metastasis formation. One major mechanism is the ability of p140Cap to interfere with ERBB2- dependent activation of Rac GTPase-controlled circuitries. Our findings point to a specific role of p140Cap in curbing the aggressiveness of ERBB2-amplified breast cancers and suggest that, due to its ability to impinge on specific molecular pathways, p140Cap may represent a predictive biomarker of response to targeted anti-ERBB2 therapies

Disentangling the impact of COVID-19 infection on clinical outcomes and preventive strategies in older persons: An Italian perspective

Italy was one of the first western countries to embrace the first wave of COVID-19 and undergo detrimental outcomes in older adults in different clinical settings, especially in those with comorbidity and frailty. In addition, older nursing home (NH) residents had significantly higher mortality rates most likely due to the increased susceptibility of infection due to combined physical vulnerability and risks linked to the NH living environment itself. Different reports throughout Italy have rapidly highlighted selected outcomes related to COVID-19 in older patients being treated in acute and long-term care (LTC) settings. However, the majority of these studies are single center studies. Thus, it remains fundamental to collect large data from prospective based-population studies in order to identify preventive and therapeutic COVID-19 risk/protective factors correlated with COVID-19 health status outcomes. In this commentary paper, we will discuss different Italian reports according to clinical settings and highlight the importance of GeroCovid Observational and GeroCovid Vax, two large population based prospective studies in Italy

Segregation scheme of indium in AlGaInAs nanowire shells

Quaternary alloys enable the independent optimization of different semiconductor properties, such as the separate tuning of the band gap and the lattice constant. Nanowire core-shell structures should allow a larger range of compositional tuning as strain can be accommodated in a more effective manner than in thin films. Still, the faceted structure of the nanowire may lead to local segregation effects. Here, we explore the incorporation of indium in AlGaAs shells up to 25%. In particular, we show the effect of In incorporation on the energy shift of the AlGaInAs single-photon emitters present in the shell. We observe a redshift up to 300 meV as a function of the group-III site fraction of In. We correlate the shift with segregation at the nanoscale. We find evidence of the segregation of the group-III elements at different positions in the nanowire, not observed before. We propose a model that takes into account the strain distribution in the nanowire shell and the adatom diffusion on the nanowire facets to explain the observations. This work provides novel insights on the segregation phenomena necessary to engineer the composition of multidinary alloys

In vitro and in vivo single-agent efficacy of checkpoint kinase inhibition in acute lymphoblastic leukemia

Background: Although progress in children, in adults, ALL still carries a dismal outcome. Here, we explored the in vitro and in vivo activity of PF-00477736 (Pfizer), a potent, selective ATP-competitive small-molecule inhibitor of checkpoint kinase 1 (Chk1) and with lower efficacy of checkpoint kinase 2 (Chk2). Methods: The effectiveness of PF-00477736 as single agent in B-/T-ALL was evaluated in vitro and in vivo studies as a single agent. The efficacy of the compound in terms of cytotoxicity, induction of apoptosis, and changes in gene and protein expression was assessed using different B-/T-ALL cell lines. Finally, the action of PF-00477736 was assessed in vivo using leukemic mouse generated by a single administration of the tumorigenic agent n-ethyl-n-nitrosourea. Results: Chk1 and Chk2 are overexpressed concomitant with the presence of genetic damage as suggested by the nuclear labeling for \u3b3-H2A.X (Ser139) in 68 % of ALL patients. In human B-and T-ALL cell lines, inhibition of Chk1/2 as a single treatment strategy efficiently triggered the Chk1-Cdc25-Cdc2 pathway resulting in a dose-and time-dependent cytotoxicity, induction of apoptosis, and increased DNA damage. Moreover, treatment with PF-00477736 showed efficacy ex vivo in primary leukemic blasts separated from 14 adult ALL patients and in vivo in mice transplanted with T-ALL, arguing in favor of its future clinical evaluation in leukemia. Conclusions: In vitro, ex vivo, and in vivo results support the inhibition of Chk1 as a new therapeutic strategy in acute lymphoblastic leukemia, and they provide a strong rationale for its future clinical investigation