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Journal of Cancer Metastasis and Treatment 2019年第12期4卷 41-48页

作者： Giovanni Lo Re Silvia Magnaldi Paolo Doretto Roberto Innocente Francesco Lo Re Medical Oncology and Immune-related tumors CRO IRCCSAviano 33081Italy Radiology AAS5 PordenonesePordenone 33170Italy Clinical pathology AAS5 PordenonesePordenone 33170Italy Radiotherapy Centro di Riferimento Oncologico(CRO)Aviano 33081Italy Chemotherapy and Medical Toxicology Study UniversityMilan 20129Italy

The most widely used chemotherapeutic combinations in locally advanced (LA) or metastatic pancreatic ductal adenocarcinoma(PDAC)areNab-Paclitaxel-Gemcitabine(Nab-PCT-GEM)andFluorouracil,Folinicacid,Oxaliplatin, and irinotecan (FOLFIRINOX). Chemo-resistance, typical of PDAC, appears to be due to the negative influence of stroma population cells, namely regulatory T cells (Treg) and myeloid-derived suppressor cells, macrophages with inhibitory effects on the antitumor activity of the innate and adaptive immune systems, and resistance to cancer treatment. Among other factors that may influence immune surveillance, constant physical activity appears to reduce the risk of cancer-related mortality and cardiovascular risk. However, this does not seem to increase the survival of patients with PDAC. The exception is our young inoperable patient. For LA head PDAC, he was treated with seven cycles of Nab-PCT-GEM and RT 50 Gy/15 fractions combined to biweekly GEM and salvage FOLFIRINOX. The five-year surviving patient travelled 15,000 km on foot and continues inexorably his "walking therapy".

关键词： Pancreatic adenocarcinoma depression physical activity Nab-paclitaxel fluorouracil regulatory T cells myeloid-derived suppressor cells

Cyclophosphamide,fluorouracil and low-dose interleukin-2 and salvage combination chemotherapy in advanced cutaneous squamous cell carcinoma

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Journal of Cancer Metastasis and Treatment 2020年第1期6卷 168-176页

作者： Giovanni Lo Re Paolo Doretto Francesco Lo Re Fabio Matrone Anna Ermacora Wally Marus Maria Antonietta Pizzichetta Sandro Sulfaro Medical Oncology and Immune-Related Tumors Centro di Riferimento Oncologico di Aviano(CRO)IRCCSAvianoPN 33081Italy Clinical Pathology AAS5 PordenonesePN 33170Italy Pharmacology and Clinical Toxicology University of MilanMilanMI 20129Italy Radiotherapy Unit Centro di Riferimento Oncologico di Aviano(CRO)IRCCSAvianoPN 33081Italy Internal Medicine AAS5 PordenonesePN 33170Italy Pathology AAS5 PordenonesePN 33170Italy Medical oncology and Cancer prevention Centro di Riferimento Oncologico di Aviano(CRO)IRCCSAvianoPN 33081Italy

A 70-year-old female with metastatic cutaneous squamous cell carcinoma(cSCC)and low-grade non-Hodgkin’s lymphoma,not amenable to cisplatin combination therapy,was treated with cyclophoshamide(Cyc)-fluorouracil(FU)-interleukin-2(IL-2)in light of high tumor immunogenicity and the potential activity of this regimen.Cyc 300 mg/m^(2)and FU 500 mg/m^(2)intravenously on day 1 and IL-24.5 MIU/day on days 3-6 and 17-20 subcutaneously every 4 weeks;Carboplatin(C)AUC 2 and paclitaxel(P)85 mg/m^(2)on days 1,8 and 15±capecitabine(Cape)every 4 weeks.After partial remission(PR)of lung metastases and local control with two cycles of first therapy followed by PR with five cycles of CP±Cape,right mastectomy was performed with evidence of viable tumor.Subsequently,the patient underwent 3 cycles of chlorambucil and is alive after 13 months of follow-up.Safety and activity of chemo-immunotherapy and salvage treatment can be achieved in cSCC.

关键词： Cutaneous squamous cell carcinoma cyclophosphamide fluorouracil interleukin-2 regulatory T cells myeloid-derived suppressor cells

Not really an aftermath.The role of actual construction in the design process of the Sydney Opera House roof

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Frontiers of Architectural Research 2023年第2期12卷 242-265页

作者： paolo Stracchi Luciano Cardellicchio paolo Tombesi School of Architecture Design and PlanningUniversity of SydneyAustralia School of Built Environment The University of New South WalesAustralia Swiss Federal Institute of Technology(EPFL) LausanneSwitzerland

For the past 50 years,the Sydney Opera House has been the subject of a prodigious hagiography of the personalities involved in its realization and their legendary querelles.Yet it remains paradoxically unexplored when it comes to its operative construction decisions,particularly those that relate to the erection of its renowned superstructure.Through the analysis of a newly discovered set of shop drawings prepared for the innovative formwork system of the iconic roof sails,the paper contributes to the construction history of the building whilst shedding light on the hitherto unacknowledged role of the general contractor in the design process.In doing so,it questions the validity of conventional assumptions about the technical division of labour in complex projects,where construction and project management tend to be kept separate from architectural and structural design,furthermore suggesting the need for broader design exegeses,combining project-based and production-based concerns.In reflecting on its import for contemporary practice,the study suggests that the revealing picture of the Sydney Opera House project,as it emerged from the cumbersome archive-based crossanalysis of the manual documentation produced for it,is in principle much easier and perhaps important to obtain today.This is due,on the one side,to availability and diffusion of digital project collaborative platforms;on the other side,to the merging and the blurring of professional and non-professional design contributions.

关键词： Construction history Shop drawings General contractor Building studies Integrated design Digital project platforms

Three-dimensional in vitro models of neuromuscular tissue

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Neural Regeneration Research 2022年第4期17卷 759-766页

作者： paolo Raffa Maria Easler Anna Urciuolo Institute of Pediatric Research IRP PadovaItaly Molecular Medicine Department University of PadovaPadovaItaly

Skeletal muscle is a dynamic tissue in which homeostasis and function are guaranteed by a very defined three-dimensional organization of myofibers in respect to other nonmuscular components,including the extracellular matrix and the nervous network.In particular,communication between myofibers and the nervous system is essential for the overall correct development and function of the skeletal muscle.A wide range of chronic,acute and genetic-based human pathologies that lead to the alteration of muscle function are associated with modified preservation of the fine interaction between motor neurons and myofibers at the neuromuscular junction.Recent advancements in the development of in vitro models for human skeletal muscle have shown that three-dimensionality and integration of multiple cell types are both key parameters required to unveil pathophysiological relevant phenotypes.Here,we describe recent achievement reached in skeletal muscle modeling which used biomaterials for the generation of three-dimensional constructs of myotubes integrated with motor neurons.

关键词： 3D organization bioengineering biomaterials motor neurons neuromuscular junction skeletal muscle models

Does divergence from normal patterns of integration increase as chromosomal fusions increase in number?A test on a house mouse hybrid zone

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Current Zoology 2020年第5期66卷 527-538页

作者： Carmelo FRuciANO paolo Colangelo Riccardo Castiglia paolo Franchini Institut de Biologie de KEcole Normale Superieure(IBENS) Ecole Normale SuperieureCNRSPSL Universite ParisParis75005France School of Biological Sciences University of PortsmouthPortsmouthP012DYUK National Research Council Research Institute on Terrestrial EcosystemsMontelibretti(RM)00010Italy Department of Biology and Biotechnology"Charles Darwin" "La Sapienza"University of RomeRome00161Italy Department of Biology Lehrstuhl fiir Zoologie und EvolutionsbiologieUniversity of KonstanzKonstanz78457Germany

Chromosomal evolution is widely considered an important driver of speciation because it can promote the establishment of reproductive barriers.Karyotypic reorganization is also expected to affect the mea n phe no type,as well as its developme nt and patter ns of phenotypic in tegrati on,through processes such as variation in genetic linkage between quantitative trait loci or between regulatory regions and their targets.Here we explore the relationship between chromosomal evolution and phenotypic integration by analyzing a well-known house mouse parapatric contact zone between a highly derived Robertsonian(Rb)race(2n=22)and populations with standard karyotype(2n=40).Populations with hybrid karyotypes are scattered throughout the hybrid zone connecting the two parental races.Using mandible shape data and geometric morphometries,we test the hypothesis that patter ns of in tegration progressively diverge from the"normal"integration pattern observed in the standard race as they accumulate Rb fusions.We find that the main pattern of integration observed between the posterior and anterior part of the mandible can be largely attributed to allometry.We find no support for a gradual increase in divergence from normal patterns of integration as fusions accumulate.Surprisingly,however,we find that the derived Rb race(2n=22)has a distinct allometric trajectory compared with the standard race.Our results suggest that either individual fusions disproportionately affect patterns of integration or that there are mechanisms which"purge"extreme variants in hybrids(e.***.reduced fitness of hybrid shape).

关键词： chromosomal races geometric morphometries hybrid zone integration modularity Robertsonian fusions

Early estimation of the number of hidden HIV infected subjects: An extended Kalman filter approach

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Infectious Disease Modelling 2023年第2期8卷 341-355页

作者： paolo Di Giamberardino Daniela Iacoviello Dept.of Computer Control and Management EngineeringSapienzaUniversity of RomeVia Ariosto 2500185RomeItaly

In the last decades several epidemic emergencies have been affecting the world,influencing the social relationships,the economics and the habits.In particular,starting in the early 080,the Acquired Immunodeficiency Syndrome,AIDS,is representing one of the most worrying sanitary emergency,that has caused up to now more than 25 million of dead patients.The infection is caused by the Human Immunodeficiency Virus,HIV,that may be transmitted by body fluids;therefore with wise behaviours the epidemic spread could rapidly be contained.This sanitary emergency is peculiar for the long incubation time:it can reach even 10 years,a long period in which the individual can unconsciously infect other subjects.The identification of the number of infected unaware people,mandatory to define suitable containment measures,is here obtained by using the extended Kalman filter applied to a noisy model in which,reasonably,only the number of infected diagnosed patients is available.Numerical simulations and real data analysis support the effectiveness of the approach.

关键词： Epidemic modeling Infection spread HIV-AIDS Extended Kalman filter

The deviation angle for one-lane roundabouts: A general mathematical formulation and application

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Journal of Traffic and Transportation Engineering(English Edition) 2022年第1期9卷 44-58页

作者： Nicola Berloco Pasquale Colonna paolo Intini Department of Civil EnvironmentalLandBuilding Engineering and ChemistryPolytechnic University of BariBari 70125Italy

Properly designed roundabouts may lead to safety improvements based on both reducing approaching speeds and controlling traffic. Measurements of deflection of vehicle trajectories are commonly used to estimate roundabout speed control. One of these measurements is the deviation angle, which is mentioned in both the Italian and Swiss road standards and, in specific conditions, can be more effective than other methods.This article presents a general mathematical formulation for linking several geometric parameters with the deviation angle in different rural and urban one-lane roundabout configurations, which is currently missing in the literature. For urban roundabouts, refuge islands for pedestrians and cyclists were considered. Based on the proposed formulation, a sensitivity analysis of the influential geometric parameters was conducted. Results suggest that an insufficient deflection of trajectories(deviation angle less than 45°) is always present for roundabouts with inscribed circle diameter less than 25 m;for urban roundabouts with refuge islands for pedestrians and cyclists having inscribed circle diameter less than34 m and orthogonal legs;and for roundabouts with angles between opposite legs smaller than 140°. The main parameters which are responsible for a decrease in the deviation angle are: a decrease in the inscribed circle diameter;a decrease in the angle between opposite legs;and an increase in the width of the circulatory lane. Some optimized procedures for roundabout design, the generalized application of the deviation angle method and alternative speed control measures in cases of small deviation angles are discussed.

关键词： Traffic engineering One-lane roundabout Roundabout deflection Deviation angle Speed control

About Open Science and Autonomy of Science

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Data Intelligence 2021年第1期3卷 52-61页

作者： paolo Budroni TU Wien A-1040 ViennaAustria

This article invites us to a concise walk through the past,offering insights defined by the major challenges science encountered during the centuries.Some lessons for today and tomorrow are enumerated in the three sections of the article,and they go beyond the relatively few perspectives offered by today’s Data Science:Open Science(OS)is what has always happened and is nothing new,because science has always sought to be open.Esthetical values played a relevant role in the past.Former scientists recognized the intrinsic relation between the way they opened science and the way they followed the principles of beauty and the sense of esthetic.Their groundbreaking heritage still inspires us in being ready to open new ways in science.Whereas Latin was the original lingua franca of European science,and English is the recent lingua franca,the new lingua franca is software.Pieces of software are the filter,which connect researchers to the world,through layers of data.They assist in observing,in choosing,and in selecting.Open scientists should be aware of the fact that their autonomy in science depends on the quality of these pieces.Another lesson is that ethics-regarded as a source of innovative activities-must be a core component of innovative processes in OS,because society needs a responsible use of data and algorithms in corresponding practices that serve OS.

关键词： Open Science Open knowledge Open society Open Education Open innovation Autonomy of science

Visual communication in social play of a hierarchical carnivore species:the case of wild spotted hyenas

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Current Zoology 2022年第4期68卷 411-421页

作者： Andrea paolo Nolfo Grazia Casetta Elisabetta Palagi Department of Biology Unit of EthologyUniversity of PisaVia A.Volta 6Pisa56126Italy Natural History Museum University of PisaVia Roma 79CalciPisa56011Italy

Communication relies on signals that can be produced via different sensory modalities to modify receivers’behavior.During social interactions,the possibility to perceive subtle visual cues enhances the use of facial expressions to exchange information.One of the most appropriate fields to explore the specific design features of visual signals is play fighting.Here,we explored the production and potential role of Relaxed Open Mouth(ROM)and Head Bobbing(HB)in regulating play fighting of wild spotted hyenas Crocuta crocuta,a highly hierarchical carnivore species.In accordance with the assumptions of the signal optimization theory,wild hyenas produced ROM and HB almost exclusively when the sender was in direct visual contact with the receiver thus suggesting that senders were attentive to the playmates’face.Contrary to HB,the sequential analysis revealed that ROM often anticipated offensive patterns such as play biting thus supporting the hypothesis that ROM,but not HB,is a metacomunicative signal.Moreover,when the offensive patterns were biased toward one of the 2 players,the session was punctuated by a higher number of ROMs.Our findings support the general hypothesis that these 2 visual signals can play different roles in the management of play fighting in this carnivore species.The complementary use of ROM and HB would suggest that spotted hyenas are highly competent and fast in processing facial displays of different nature to correctly“read others’intentions”and respond with appropriate motor actions to avoid misunderstanding during one of the most multifaceted and risky social interaction.

关键词： Crocuta crocuta head and facial signals head bobbing metacommunication play fighting relaxed open mouth display

Temperature-and vacancy-concentration-dependence of heat transport in Li_(3)ClO from multi-method numerical simulations

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npj Computational Materials 2022年第1期8卷 197-205页

作者： paolo Pegolo Stefano Baroni Federico Grasselli SISSA—Scuola Internazionale Superiore di Studi Avanzati 34136TriesteItaly CNR-Istituto Officina dei Materiali SISSA34136TriesteItaly COSMO—Laboratory of Computational Science and Modelling IMXÉcole Polytechnique Fédérale de Lausanne1015LausanneSwitzerland

Despite governing heat management in any realistic device,the microscopic mechanisms of heat transport in all-solid-state electrolytes are poorly known:existing calculations,all based on simplistic semi-empirical models,are unreliable for superionic conductors and largely overestimate their thermal conductivity.In this work,we deploy a combination of state-of-the-art methods to calculate the thermal conductivity of a prototypical Li-ion conductor,the Li_(3)ClO antiperovskite.By leveraging ab initio,machine learning,and force-field descriptions of interatomic forces,we are able to reveal the massive role of anharmonic interactions and diffusive defects on the thermal conductivity and its temperature dependence,and to eventually embed their effects into a simple rationale which is likely applicable to a wide class of ionic conductors.

关键词： transport conductivity eventually