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Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern

Journal of Molecular Cell Biology 2024年第3期16卷 9-23页

作者： Ilaria Frasson Linda Diamante Manuela Zangrossi Elena Carbognin Anna Dalla Pietà Alessandro Penna Antonio Rosato Ranieri Verin filippo torrigiani Cristiano Salata Marìa Paula Dizanzo Lorenzo Vaccaro Davide Cacchiarelli Sara N.Richter Marco Montagner Graziano Martello Department of Molecular Medicine University of PaduaPadua 35121Italy Department of Biology Armenise/Harvard Pluripotent Stem Cell Biology LaboratoryUniversity of PaduaPadua 35131Italy Department of Surgery Oncology and GastroenterologyUniversity of PaduaPadua 35128Italy Veneto Institute of Oncology IOV-IRCCS Padua 35128Italy Department of Comparative Biomedicine and Food Science University of PaduaPadua 35020Italy Telethon Institute of Genetics and Medicine(TIGEM) Armenise/Harvard Laboratory of Integrative GenomicsPozzuoli 80078Italy Department of Translational Medicine University of Naples Federico IINaples 80138Italy School for Advanced Studies Genomics and Experimental Medicine ProgramUniversity of Naples Federico IINaples 80138Italy Microbiology and Virology Unit Padua University HospitalPadua 35128Italy

The high mutation rate of SARS-CoV-2 leads to the emergence of multiple variants,some of which are resistant to vaccines and drugs targeting viral *** host dependency factors,*** proteins required for viral replication,would help prevent the development of ***,it remains unclear whether different SARS-CoV-2 variants induce conserved cellular responses and exploit the same core host *** this end,we compared three variants of concern and found that the host transcriptional response was conserved,differing only in kinetics and *** regularly interspaced short palindromic repeats screening identified host genes required for each variant during *** of the genes were shared by multiple *** validated our hits with small molecules and repurposed the US Food and Drug Administration-approved *** the drugs were highly active against all the tested variants,including new variants that emerged during the study(Delta and Omicron).Mechanistically,we identified reactive oxygen species production as a key step in early viral *** such as N-acetyl cysteine(NAC)were effective against all the variants in both human lung cells and a humanized mouse *** study supports the use of available antioxidant drugs,such as NAC,as a general and effective anti-COVID-19 approach.

关键词： SARS-CoV-2 variants of concern host dependency factors antivirals N-acetyl cysteine

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Bacterial cell-free expression technology to in vitro systems engineering and optimization

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Synthetic and Systems Biotechnology 2017年第2期2卷 97-104页

作者： filippo Caschera Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris(ESPCI Paris) CNRS UMR 708310 Rue Vauquelin75231 Paris Cedex 05France

Cell-free expression system is a technology for the synthesis of proteins in *** system is a platform for several bioengineering projects,***-free metabolic engineering,evolutionary design of experiments,and synthetic minimal cell *** cell-free protein synthesis system(CFPS)is a robust tool for synthetic *** bacteria lysate,the DNA,and the energy module,which are the three optimized sub-systems for in vitro protein synthesis,compose the integrated ***,an optimized *** cell-free expression system can produce up to^2.3 mg/mL of a fluorescent reporter ***,I will describe the features of ATP-regeneration systems for in vitro protein synthesis,and I will present a machine-learning experiment for optimizing the protein yield of *** cell-free protein synthesis ***,I will introduce experiments on the synthesis of a minimal cell using liposomes as dynamic containers,and *** cell-free expression system as biochemical platform for metabolism and gene *** can be further integrated with other technologies for novel applications in environmental,medical and material science.

关键词： Cell-free protein synthesis Engineering Optimization Polysaccharide ATP-regeneration Machine-learning Synthetic minimal cell

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“Noisy”issues in road acoustics:A white paper

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Journal of Road Engineering 2022年第1期2卷 61-69页

作者： filippo Giammaria Praticò DIIES Department University Mediterranea of Reggio CalabriaReggio Calabria 89124Italy

Despite almost a century of studies dealing with traffic noise,researchers and practitioners still face old and new issues when designing a low-noise *** that,this manuscript aims at focusing on a number of unsolved questions,namely theoretical or technological.1)Is it viable to balance diverse road-related needs(i.e.,noise,expected life,texture levels,and friction)?2)How much does the pavement material affect its acoustic performance(the remaining factors being constant)?3)How much reliable is the relationship between road texture and mixture aggregate gradation?Based on the analysis of these issues,it emerges that:1)optimal pavement design involves complex mix optimization and there are theoretical and practical bases to set up a balanced approach to address the complexity of pavement design;2)high percentages of crumb rubber could optimise road acoustic response but this latter has a relationship with the tyre/road noise(expressed,for example,in terms of close proximity index)that calls for further investigation;3)aggregate gradation appears to be a reliable basis to predict surface texture and therefore,under given boundary conditions,tyre/road noise;and 4)further studies and investigations are needed in terms of local calibration of deterioration curves and setting up of a sound method to assess the frequency response of asphalt concretes and to govern on-site noise indicators based on mixture properties.

关键词： Aggregate gradation Complex design Noise Surface texture Tyre/road interaction

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Fatigue strength of Al7075 notched plates based on the local SED averaged over a control volume

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Science China(Physics,Mechanics & Astronomy) 2014年第1期57卷 30-38页

作者： BERTO filippo LAZZARIN Paolo University of Padova Department of Management and Engineering Stradella San Nicola 3 36100 Vicenza Italy

When pointed V-notches weaken structural components, local stresses are singular and their intensities are expressed in terms of the notch stress intensity factors （NSIFs）. These parameters have been widely used for fatigue assessments of welded struc- tures under high cycle fatigue and sharp notches in plates made of brittle materials subjected to static loading. Fine meshes are required to capture the asymptotic stress distributions ahead of the notch tip and evaluate the relevant NSIFs. On the other hand, when the aim is to determine the local Strain Energy Density （SED） averaged in a control volume embracing the point of stress singularity, refined meshes are, not at all, necessary. The SED can be evaluated from nodal displacements and regular coarse meshes provide accurate values for the averaged local SED. In the present contribution, the link between the SED and the NSIFs is discussed by considering some typical welded joints and sharp V-notches. The procedure based on the SED has been also proofed to be useful for determining theoretical stress concentration factors of blunt notches and holes. In the second part of this work an application of the strain energy density to the fatigue assessment of A17075 notched plates is presented. The experimental data are taken from the recent literature and refer to notched specimens subjected to different shot peening treatments aimed to increase the notch fatigue strength with respect to the parent material.

关键词： strain energy density control volume coarse mesh

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Use of the RegCM System over East Asia： Review and Perspectives

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Engineering 2017年第5期3卷 766-772页

作者： Xuejie Gao filippo Giorgi Climate Change Research Center Institute of Atmospheric Physics Chinese Academy of Sciences Beijing 100029 China The Abdus Salam International Center.for Theoretical Physics Trieste 34151 Italy

The Abdus Salam International Center for Theoretical Physics （ICTP） RegCM system is one of the most commonly used regional climate models （RCMs） over the East Asia region, In this paper, we present a brief review of the RegCM system and its applications to the East Asia region. The model history and plans for future development are described, Previous and ongoing applications, as well as the advantages and biases found in the model system over the East Asia region, are summarized, The model biases that exist are mainly found in the cold seasons, and are characterized by a warm bias at high latitudes and underestimation of precipitation in the south. These biases are similar to those of most global climate models （GCMs）, Finally, future plans on the application and development of the model, and specifically on those within the context of the Coordinated Regional Climate Downscaling Experiment （CORDEX）, are introduced. This paper is intended to serve as a reference for future users of the RegCM system within the East Asia region.

关键词： Regional climate model China Climate change Community land model

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Ritt's theorem and the Heins map in hyperbolic complex manifolds

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Science China Mathematics 2005年第z1期48卷 238-243页

作者： Marco Abate filippo Bracci Dipartimento di Matematica Università di Pisa Largo Pontecorvo 556127 PisaItalyDipartimento di Matematica Università di Roma "Tor Vergata"Via della Ricerca Scientifica00133 RomaItaly

Let X be a Kobayashi hyperbolic complex manifold, and assume that X does not contain compact complex submanifolds of positive dimension (e.g., X Stein). We shall prove the following generalization of Ritt's theorem: every holomorphic self-map f: X →X such that f(X) is relatively compact in X has a unique fixed point τ(f) ∈ X, which is attracting. Furthermore, we shall prove that τ(f) depends holomorphically on f in a suitable sense, generalizing results by Heins, Joseph-Kwack and the second author.

关键词： holomorphic self-map, fixed point, Wolff point, Ritt's theorem, Heins map, Stein manifold.

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Multiplication and division of the orbital angular momentum of light with diffractive transformation optics

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Light(Science & Applications) 2019年第1期8卷 111-123页

作者： Gianluca Ruffato Michele Massari filippo Romanato Department of Physics and Astronomy‘G.Galilei’ University of Padovavia Marzolo 835131 PadovaItaly LaNN Laboratory for Nanofabrication of NanodevicesEcamRicertCorso StatiUniti 435127 PadovaItaly CNR-INFM TASC IOM National Laboratory S.S.14 Km 163.534012 TriesteItaly

We present a method to efficiently multiply or divide the orbital angular momentum(OAM)of light beams using a sequence of two optical *** key element is represented by an optical transformation mapping the azimuthal phase gradient of the input OAM beam onto a circular *** combining multiple circular-sector transformations into a single optical element,it is possible to multiply the value of the input OAM state by splitting and mapping the phase onto complementary circular ***,by combining multiple inverse transformations,the division of the initial OAM value is achievable by mapping distinct complementary circular sectors of the input beam into an equal number of circular phase *** elements have been fabricated in the form of phase-only diffractive optics with high-resolution electron-beam *** tests confirm the capability of the multiplier optics to perform integer multiplication of the input OAM,whereas the designed dividers are demonstrated to correctly split up the input beam into a complementary set of OAM *** elements can find applications for the multiplicative generation of higher-order OAM modes,optical information processing based on OAM beam transmission,and optical routing/switching in telecom.

关键词： optics circular complementary

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Inverse design of truss lattice materials with superior buckling resistance

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npj Computational Materials 2022年第1期8卷 2361-2372页

作者： Marco Maurizi Chao Gao filippo Berto Department of Mechanical and Industrial Engineering Norwegian University of Science and Technology(NTNU)Trondheim7491Norway

Manipulating the architecture of materials to achieve optimal combinations of properties(inverse design)has always been the dream of materials scientists and *** represent an efficient way to obtain lightweight yet strong materials,providing a high degree of *** massive research has been done on lattice architectures,the inverse design problem of complex phenomena(such as structural instability)has remained *** deep neural network and genetic algorithm,we provide a machine-learning-based approach to inverse-design non-uniformly assembled *** basic building blocks,our approach allows us to independently control the geometry and topology of periodic and aperiodic *** an example,we inverse-design lattice architectures with superior buckling performance,outperforming traditional reinforced grid-like and bio-inspired lattices by~30–90%and 10–30%,*** results provide insights into the buckling behavior of beam-based lattices,opening an avenue for possible applications in modern structures and infrastructures.

关键词： buckling inverse lattice

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Genome-wide investigation to assess copy number variants in the Italian local chicken population

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Journal of Animal Science and Biotechnology 2024年第2期15卷 563-577页

作者： filippo Cendron Martino Cassandro Mauro Penasa Department of Agronomy FoodNatural ResourcesAnimals and Environment(DAFNAE)University of PadovaViale Dell’Universita 1635020 LegnaroPDItaly Federazione Delle Associazioni Nazionali Di Razza E Specie Via XXIV Maggio 4300187 RomeItaly

Background Copy number variants(CNV)hold significant functional and evolutionary *** ongoing CNV studies aim to elucidate the etiology of human diseases and gain insights into the population structure of ***-density chips have enabled the detection of CNV with increased resolution,leading to the identification of even small *** study aimed to identify CNV in local Italian chicken breeds and investigate their distribution across the *** Copy number variants were mainly distributed across the first six chromosomes and primarily associated with loss type *** majority of CNV in the investigated breeds were of types 0 and 1,and the minimum length of CNV was significantly larger than that reported in previous ***,a high proportion of the length of chromosome 16 was covered by copy number variation regions(CNVR),with the major histocompatibility complex being the likely *** the genes identified within CNVR,only those present in at least five animals across breeds(n=95)were discussed to reduce the focus on redundant *** of these genes have been associated to functional traits in ***,several CNVR on different chromosomes harbor genes related to muscle development,tissue-specific biological processes,heat stress resistance,and immune *** trait loci(QTL)were also analyzed to investigate potential overlapping with the identified CNVR:54 out of the 95 gene-containing regions overlapped with 428 QTL associated to body weight and size,carcass characteristics,egg production,egg components,fat deposition,and feed *** The genomic phenomena reported in this study that can cause changes in the distribution of CNV within the genome over time and the comparison of these differences in CNVR of the local chicken breeds could help in preserving these genetic resources.

关键词： Chicken Copy number variant Conservation Local breed SNP

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Improving the approach to non-cardiac syncope in the emergency department observation unit

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World Journal of Emergency Medicine 2023年第2期14卷 128-132页

作者： filippo Numeroso Ivo Casagranda Emergency Department University Hospital of ParmaParma 43126Italy Academy of Emergency Medicine and Care(AcEMC) Pavia 27100Italy

Syncope is a rather frequent condition,responsible for1.0%–1.5%of emergency department (ED) visits.[1]Even if the development of clinical guidelines has improved the ED management of syncope,[2]the hospitalization rate is still very high (up to 50%),especially compared with the incidence of short-term adverse events,which is11%globally,but decreases to less than 4%when events already diagnosed in the ED are excluded,[1]meaning that most patients will not benefit from admission.

关键词： globally department syncope

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