You can search using the name of your loved one or any family name for current or past services entrusted to our firm Ordering flowers from our site ensures that your order will reach us or the family in a timely manner and your gesture of support will remain acknowledged in the Book of Memories for future generations We only work with local florists so we can maintain the sense of urgency and quality of your selections We thank you for helping to support the family during their time of need and will fondly remember your kind gesture The Family Interactive feature enhances An Amazing Life Authorized family members can securely access their loved one's memorial website settings at any time Please enter the name and email details so that we can send your friend a link to the online tribute No names or addresses will be collected by using this service Provide comfort for the family by sending flowers or planting a tree in memory of Robyn Pontremoli Please enter your question or comment below: A receipt has been emailed to the address provided Agreement with Policy and Continued Use of Site Family and friends are coming together online to create a special keepsake Every memory left on the online obituary will be automatically included in this book We encourage you to share your most beloved memories of Robyn here so that the family and other loved ones can always see it and can even comment on those shared by others it will also remain on this memorial website in perpetuity PLEASE NOTE: The reproduction of any copyrighted images is forbidden without express written permission from the copyright holder any image in violation of any copyright laws 3 trees were planted in the memory of Robyn Pontremoli you will receive two daily updates containing all new stories one week prior to the anniversary of death The email will only serve as a reminder should you choose to connect with the family at what will no doubt be a difficult time Please select your relationship to the deceased and add your email address before submitting The shareholders’ meeting of Motor Valley has appointed Andrea Pontremoli as the new President The CEO and shareholder of the Dallara Group succeeds Ducati’s CEO Claudio Domenicali at the helm of the association that brings together the most famous brands from the Motor Valley of Emilia-Romagna Managing Director of the Misano World Circuit Marco Simoncelli “It is a great honor for me to take on the role of President of Motor Valley Development an organization that represents the passion and innovation of our region I assume this role with a spirit of service continuing the work done by Claudio Domenicali to whom I express my gratitude,” said Andrea Pontremoli “My commitment will be to enhance the heritage we have looking to the future with the same determination and vision that have always characterized the companies of our region we will continue to make the Motor Valley a global point of reference for two and four wheels with the goal of remaining at the forefront both technically and as a social system knowing that our strength will be the ecosystem we manage to build and maintain.” Here are the words of outgoing President Claudio Domenicali: “Holding the role of President of Motor Valley Development from 2019 to today has been a privilege and a great responsibility This region represents a unique excellence in the world not only from an industrial perspective but also from a tourist and brings together the most prestigious Italian brands in the two and four-wheel industry guardians of an invaluable heritage of motor expertise and technology Contributing to its enhancement has been a great source of pride for me I pass the baton to Andrea – a passionate friend and professional – confident that he will lead the future of the Motor Valley with vision and dedication.” Two women in oncology have been named recipients of the International Gynecologic Cancer Society’s 2024 Global Humanitarian Award organizations or programs that work to improve access to quality gynecologic oncology services in low- to middle-income countries or in areas of need within more developed nations,” according to a press release Pontremoli Salcedo directs training and education in cervical cancer prevention for programs in Texas she is a gynecologist who conducts research on cervical cancer prevention dedicates time to International Gynecologic Cancer Society (IGCS) Global Gynecologic Oncology Fellowship Program site in Mozambique as an international mentor and has led Project Extension for Community Healthcare Outcomes (ECHO) sessions Ismail-Pratt leads the International Papillomavirus Society (IPVS) ECHO committee which provides a support platform for physicians on management of patients with HPV She is also a founding member of the Asia Pacific HPV Coalition that works to address HPV-associated issues in the Asia Pacific through research and advocacy initiatives and has helped to establish and support a preinvasive training program and colposcopy workshops in Cambodia Press Release Get the latest news and education delivered to your inbox The email address associated with your Healio account is: If you would like to edit or change the email address that your subscriptions and alerts are sent to You'll receive reminders to complete your saved activities from Healio CME The score of Pontremoli La Cisa: Plaia 11, Ulivi, Adamo 4, Mazzetti 2, Morillo 10, Spagnoli 4, Rocchi 24, Montano 6, Reggiani, Longinotti, Fenucci, Coduri. Coach: Novelli. is a place where the Etruscan and medieval past is intertwined with modern life the “Florence of Lunigiana,” amazes with its elegant squares and Renaissance buildings that conceal traces of the past that linked the town to the Grand Duchy of Tuscany where life flows slowly and local traditions Here the mountains are not just a place to explore-it is a way of life Life in the Apennines is marked by the rhythms of nature and ancient farming traditions still survive to this day Mountains are a constant and inescapable presence for those who live on the Apuan coast and in Lunigiana such as the marble of the Apuan Alps or the chestnuts of the Apennines have been the sustenance and wealth of this land for centuries; they have created a direct link between the mountains and the people who live here Life in the mountains has never been easy: the harsh climate steep terrain and communication difficulties have required an extraordinary ability to adapt This same strength is reflected in the tenacity and proud character of the local communities The mountainous lands of Lunigiana and the Apuan Alps have also preserved their cultural and gastronomic traditions insulating them from the sudden changes brought by modernity Ancient customs manage to survive here thanks to the link with this mountainous landscape that protects them and keeps them alive was already revered by the ancient Ligurians as a mystical place mountains are seen not only as a physical place but as a space in which man can approach the transcendent finding peace and connection with something greater than himself The history of Italy can be said to have passed between the Apuan Alps and Lunigiana: the position of the Apuan and Lunigiana mountains made this territory a borderland but also a strategic communication route for many centuries the territory was the boundary between Regio VII Etruria and Regio IX Liguria a separation not only geographical but also cultural The Apuo-Lunense mountains then formed a natural line of defense: throughout history they were exploited as a natural defense against invasions and attacks serving as a bulwark to protect the local populations the routes through Lunigiana were traversed by travelers and soldiers who used these paths to cross from northern Italy to Rome and vice versa were crucial for crossing the barrier of the Apennines From here then passed the salt routes used to transport the precious mineral from the Ligurian Sea northward to the Po Valley and the cities of Emilia and beyond The border position then made large parts of the territory of today’s province of Massa-Carrara a contested land between different political entities The crossroads position of these areas enriched the territory but always nevertheless attached to their lands dotted with castles and fortifications (from Piagnaro Castle in Pontremoli to Malaspina Castle in Massa from Brunella Fortress in Aulla to Castruccio’s Tower in Avenza di Carrara not to mention the many castles in Lunigiana: Fosdinovo built to control the passes and defend the territory testifies to the strategic role of the entire area in the past Massa-Carrara’s strategic position made this land a protagonist of encounters and clashes transforming it into a place of cultural and historical richness the mountain passes and villages of the province tell this story of passages speaking to visitors who want to discover an area where the mountains are not just a barrier but a bridge between the past and the future The mountains of Massa-Carrara are then deeply linked to the art and culture of this province so much so that they themselves become muses and material for immortal masterpieces traditions and mountain landscapes become protagonists which celebrates the importance of Apuan marble in art and culture (here it is possible to discover how marble has been extracted from the mountains and transformed into works of art since theRoman times work tools and models that testify to the inseparable link between the mountains and Carrara’s artistic tradition) to the quarries themselves where you can visit the places where the mountains are “carved out” and understand how their material has become sculptures buildings and monuments all over the world the places scattered throughout the territory that offer living evidence of this link: the Carrara Cathedral is one of the finest examples of the link between mountain marble and sacred art The façade is built entirely of Apuan marble while inside one can admire marble works with which one can admire the beauty and purity of the material which was the residence of the Cybo-Malaspina family Apuan marble was used to decorate interiors and exteriors showing how the material of the mountains influenced the art and architecture of the Renaissance and Baroque periods Going up to Pontremoli, we visit the Museum of the Stele Statues, which preserves the stele statues mysterious prehistoric stone sculptures carved by the first inhabitants of the mountains: these anthropomorphic figures testify to a spiritual and artistic connection with the mountain landscape that goes back millennia as in all the villages and castles of Lunigiana This link between mountains and art is still alive: in the center of Carrara the Padula Park hosts contemporary artworks that dialogue with the landscape marble sculptures displayed in a natural setting to remind us of the inseparable relationship between art and nature that these lands have always experienced as part of themselves In every corner of the province of Massa-Carrara from monumental quarries to medieval villages art and mountains are intertwined in an eternal dialogue offering anyone who comes here the opportunity to discover how nature can become art and how art can give voice to nature The mountains here are not just an element of the landscape but a symbol of resilience and identity for the communities that live at their foot these mountains have been a physical and cultural barrier but also a source of inspiration and protection the mountains of Massa-Carrara were the scene of dramatic events: the Gothic Line ran through these lands and what happened on these mountains left deep scars behind but not only that: in this land the history of the Resistance was made And even today the paths of the mountains tell stories of freedom keeping the memory of those difficult days alive And it should not be forgotten that the mountains of Massa-Carrara have always inspired artists Their imposing forms and changing landscapes have been celebrated in works of art and literature and they continue to be a source of inspiration for anyone who visits them the Apuan Alps have inspired poets such as Gabriele D’Annunzio “Marmoreal crown of threatening points from their pride assumed”: this is one of the many verses about the Apuan Alps that can be found inAlcyone But mountains do not only inspire artists: for those who live in these lands they represent a deep connection with their history a connection with nature and a call to simplicity and authenticity the symbol of a thousand-year history and a culture rooted in nature a former rector of the University of Genoa and an honorary member of the American Society for Biochemistry and Molecular Biology since 1984 Pontremoli earned a degree in medicine and surgery at the University of Genoa in 1949 He became an assistant in the university’s Institute of Physiology where his research focused on metabolism Arturo Bonsignore invited Pontremoli to join the Institute of Biochemistry at Genoa Bonsignore had been studying enzymes of glycolytic metabolism and became interested in the recently discovered pentose phosphate pathway which was found to generate NADPH for reductive cell biosynthesis for the synthesis of nucleotides and nucleic acids Bonsignore sent Pontremoli to the National Institutes of Health to work with Bernard Horecker, the biochemist who had discovered this new metabolic pathway. (Horecker was an ASBMB member from 1947 until his death in 2010, and his work on the pentose phosphate pathway was the subject of a 2005 Centenary Classic in the Journal of Biological Chemistry.) This trip to the U.S marked the beginning of a collaboration that lasted decades with the two researchers traveling back and forth to each other’s labs Pontremoli accepted a full professorship at the University of Ferrara in 1963 then moved back to Genoa seven years later He expanded his work to the study of proteases Pontremoli worked to modernize biochemistry in Italy of the University of Genoa in 1990 and served in that role for 14 years opening dialogue with municipal and regional officials and helping to establish the Italian Institute for Technology He was a member of the Accademia Nazionale dei Lincei a venerable European scientific institution in Rome Giorgio Parisi, president of the Accademia, told an obituary writer (in Italian) (Pontremoli) lived as a protagonist of the glorious biochemistry of the pioneers who discovered the fundamental metabolic pathways with brilliant intuition strongly linked to chemical knowledge.” Become a member to receive the print edition four times a year and the digital edition monthly This article was written by a member or members of the ASBMB Today staff and we’ll send you a weekly email with recent articles which recognizes exceptional juniors and seniors pursuing degrees in the molecular life sciences Learn about the candidates running for ASBMB President Nominating Committee and Publications Committee Learn how the JBC associate editor went from milking cows on a dairy farm to analyzing kinases in the lab He was an associate professor of biochemistry at the University of Colorado Boulder and co-founder of the biotech company Prometheus Materials MOSAIC scholar Stanna Dorn uses total synthesis to recreate rare bacterial natural products with potential therapeutic applications Graduate student Ari Paiz describes how her love of science and art blend to make her an effective science communicator Managing IP is part of Legal Benchmarking Limited Copyright © Legal Benchmarking Limited and its affiliated companies 2025 Accessibility | Terms of Use | Privacy Policy | Modern Slavery Statement The content you are trying to view is exclusive to our subscribers The views expressed in these interviews are those of the interviewees and do not necessarily represent the positions of the firms or companies they represent ▲ Back to top of category list You have reached the limit for gifting for this month Please enable JS and disable any ad blocker Via Francigena 👣 19 km on foot – Wednesday 19 August Today we start the day by entering the region of Tuscany: the land of cypress hills I’m super excited to be here: I lived in Florence for 6 years and I already feel at home I expect a lot of amazing local food waiting for us in the coming weeks 😋 – I can’t wait to explore every aspect of the popular Tuscan section of the Via Francigena Today we were accompanied by a group of local walkers from the CAI (Club Alpino Italiano) At our departure from the church of the Cisa Pass we had a brief institutional meeting with the mayor of Pontremoli We then walked through the Tuscan gate of the Via Francigena a well-known wooden arch just behind the church of the Pass We were all expecting to spend the entire day descending from the mountain down towards Pontremoli but the Appennini mountain chain is never that straightforward…we started the day with quite a climb and continued with a lot of ups and downs today’s stage ended up being harder than I thought – definitely harder than yesterday’s climb to the Pass As we progressively descended to a lower elevation I could feel the sun becoming stronger on my skin Luckily many sections of the path were in the forest with all the up-and-down shapes of the Appennini We then came across a pilgrim walking in the “wrong” direction who has just finished his service as a Swiss guard in the Vatican City This is a common practice for Swiss guards: as they retire they walk from their work position in Rome back to Switzerland And Florent was not the only pilgrim walking in the opposite direction that we met today: we also met a brave man from Los Angeles who started walking in Rome and is heading to Canterbury we crossed a couple of charming towns: Groppoli where a local offered us his own homemade red wine (at 11 am just before another steep hill); and Groppodalosio a 2-years old accommodation facility that Greta and Marco decided to build after walking and falling in love with this stage of the route in a new age / hippie style that soothes and relaxes you as soon as you step inside and the owners offered us some coffee to recharge We decided to leave a donation for Temperance and to interview the couple to learn and share their practice with all Road to Rome followers After crossing the Via Francigena bridge in Groppodalosio we came to Casalina and to the small fraction of Toplecca a nomad tent used as an accommodation facility too One last steep descend and we arrived in Pontremoli we were welcomed in the main square by the mayor and by a group of flag-throwers who performed for us A very warm welcome in Toscana; I had no doubt – The stunning landscape of the Appennini mountains – Meeting other pilgrims and learning about their personal and spiritual quests – Taking inspiration from Greta and Marco’s Tempere and from the yurt in Toplecca on how pilgrims can help each other Massimo & Daniele (@walkingforcharity & @il_cammino_per_salus_pueri) F.A.Q © Associazione Europea delle Vie Francigene | C.F. 91029880340 – P.IVA 02654910344 Powered by ItinerAria Privacy | Cookie Policy  | Legal Notice  © Associazione Europea delle Vie Francigene | C.F Powered by ItinerAria .st1{fill-rule:evenodd;clip-rule:evenodd;fill:#2a2a2a}By Grant Segall, The Plain DealerTerri Pontremoli [pon-TREH-moe-lee] went from playing classical violin to leading the Tri-C JazzFest The festival's 38th edition takes place June 22-24 Favorite locally owned restaurants: Nighttown Terri: It's a music about freedom and soulfulness There's an openness and an expansiveness It incorporates everything from Latin music to church music to hip-hop It's sophisticated but also down home People don't sit around and go "Huh?" They go "Wow!" Terri: It's a unique combination of education and performance We have a mission to make jazz accessible to everybody of all backgrounds It's a year-round program that culminates in a summer destination festival We're teaching and presenting throughout the year What's special about JazzFest '17 Terence Blanchard's "Blue Note Sessions" is a world stage premiere of the music he wrote for the movie "The Comedian." Diego Figueiredo is a guitar virtuoso Tell us a little of JazzFest's long history Terri: It started in 1980 as a two-day event where high school band kids came in and played Then they'd play together at Playhouse Square The festival brings in special guests and master classes for the jazz and the recording programs We've had Terence Blanchard the past two years this great trumpet player and composer for many films Kids also come here on Saturdays to study jazz That's when Dominick Farinacci was exposed to Winton Marsalis Trumpeter Curtis Taylor and drummer Jerome Jennings also studied here on Saturdays the festival became 10 days in April in all different venues But April's a very busy time in Cleveland so we moved it in 2014 to June and made it a weekend festival in Playhouse Square There's a free party outside and a stage presenting 18 of Cleveland's best bands who died in March after many years of helping Tri-C Terri: You see Tommy's name on our building [Gill and Tommy LiPuma Center for Creative Arts] I read about him in '02 and saw he was from Cleveland and said we've got to get him involved I helped get the Cleveland Museum of Art to show his 20th-century American painting collection They also incorporated his platinum records and trophies we celebrated Tommy's 80th birthday with a concert by Jarreau But we're so happy Tommy was there to enjoy it Terri: The great Ella Fitzgerald in the '90's she looked so frail and had a manager who was so carefully protecting her She couldn't remember her bass player's name but she remembered all the words and scats "She's not doing an encore." She said "Move out of my way." She did three encores I picked him up at the airport that evening and drove him right to the stage just on time but we moved to Parma Heights when I was 5 except for a year in Omaha with their symphony Now my mom and sister and her family and I are all in Cleveland Heights Terri: My father was a jazz guitar player on weekends He thought it was really important for his kids to study classical music I pursued classical violin for many years before finding my passion in jazz My sister Anita and i were the Duo Pontremoli I also hired musicians for traveling shows at Playhouse Square and played in the pit with them I found myself playing shows for Benson or Sammy Davis Jr I became an administrator for the Cleveland Opera working at community outreach and educational shows in schools It evolved into writing grants and raising money and becoming the advocate for jazz Then I left to direct the Cleveland Arts Prize for a year and the Detroit Jazz Festival for a few years I go to the Cedar-Lee to see all the movies you don't see other places I can walk to Little Italy and the Rising Star there I love the lemon cake at Corbo's and of course the cassata cake I can walk to Cedar-Fairmount and enjoy Vero and Nighttown I see so many national and local artist friends come through there For more information, see tri-c.edu/jazzfest Use of and/or registration on any portion of this site constitutes acceptance of our User Agreement, (updated 8/1/2024) and acknowledgement of our Privacy Policy, and Your Privacy Choices and Rights (updated 1/1/2025) © 2025 Advance Local Media LLC. All rights reserved (About Us) The material on this site may not be reproduced except with the prior written permission of Advance Local Community Rules apply to all content you upload or otherwise submit to this site YouTube's privacy policy is available here and YouTube's terms of service is available here Ad Choices \n m_gallery = \"my_cleveland_terri_pontremoli_\";\n m_gallery_id = \"22899221\";\n m_gallery_title = \"My Cleveland: Terri Pontremoli of Tri-C JazzFest\";\n m_gallery_blog_id = \"4501\";\n m_gallery_creation_date = \"Monday 2:24 PM\";\n m_gallery_permalink = \"http://photos.cleveland.com/4501/gallery/my_cleveland_terri_pontremoli_/index.html\";\n m_gallery_json = \"https://blog.cleveland.com/photogallery/4501/22899221.json\";\n m_gallery_pagetype = \"embed\";\n m_gallery_type = \"photo\";\n <\/script>\n Gallery: My Cleveland: Terri Pontremoli of Tri-C JazzFest Volume 9 - 2018 | https://doi.org/10.3389/fmicb.2018.00854 Hepatitis C virus (HCV) belongs to the Hepacivirus genus and is genetically heterogeneous with seven major genotypes further divided into several recognized subtypes HCV origin was previously dated in a range between ∼200 and 1000 years ago Hepaciviruses have been identified in several domestic and wild mammals the largest viral diversity being observed in bats and rodents The closest relatives of HCV were found in horses/donkeys (equine hepaciviruses the origin of HCV as a human pathogen is still an unsolved puzzle Using a selection-informed evolutionary model we show that the common ancestor of extant HCV genotypes existed at least 3000 years ago (CI: 3192–5221 years ago) with the oldest genotypes being endemic to Asia EHV originated around 1100 CE (CI: 291–1640 CE) These time estimates exclude that EHV transmission was mainly sustained by widespread veterinary practices and suggest that HCV originated from a single zoonotic event with subsequent diversification in human populations We also describe a number of biologically important sites in the major HCV genotypes that have been positively selected and indicate that drug resistance-associated variants are significantly enriched at positively selected sites HCV exploits several cell-surface molecules for cell entry but only two of these (CD81 and OCLN) determine the species-specificity of infection Herein evolutionary analyses do not support a long-standing association between primates and hepaciviruses and signals of positive selection at CD81 were only observed in Chiroptera No evidence of selection was detected for OCLN in any mammalian order These results shed light on the origin of HCV and provide a catalog of candidate genetic modulators of HCV phenotypic diversity Hepatitis C virus (HCV, genus Hepacivirus, family Flaviviridae) is a hepatotropic human pathogen with an estimated worldwide seroprevalence around 2.8% (Mohd Hanafiah et al., 2013) we apply an evolutionary approach to shed light into HCV origin to analyze its adaptation to human populations and to verify if the emergence of drug-resistant variants is a result of positive selection We also analyzed the most important cell-surface molecules that mediate HCV cell entry to determine whether HCV or related hepaciviruses exerted a selective pressure on these receptors and whether selection was particularly strong in specific mammalian orders or superorders The cutoff p-value was set to 0.01 in both GARD and RDP4 No method detected recombination in any alignment After running a codon model selection analysis in HYPHY (Delport et al., 2010), gene trees were generated by maximum-likelihood using phyML with the approximate likelihood-ratio test (aLRT) method (Guindon et al., 2010) Only sites detected by both methods were considered as positively selected Very similar results were obtained using the gene tree obtained with PhyML or the species tree as inputs for PAML analysis The NS5B region we used for dating is non-recombining, as assessed by GARD and RDP4 analyses of the entire non-structural portion of the genome. This region was selected because it is one of the most conserved across HCV genotypes (Kapoor et al., 2011) and required very minor filtering The tMRCA of EHV/CHV was estimated on a phylogeny of 18 sequences with complete coding sequence information: 17 EHV isolated from horses or donkeys and 1 CHV (Kapoor et al., 2011; Burbelo et al., 2012; Walter et al., 2016) (Supplementary Table S3) GUIDANCE detected no uncertainty in the alignments (all codons had a score > 0.9) and GARD detected a breakpoint at position 6729 RDP4 detected a breakpoint at position 6747 The terminal 2145 nucleotides were thus removed and the resulting alignment was used for tree construction and tMRCA estimate Evidence for temporal structure was obtained for both phylogenies (NS5B: r = 0.25 The PL method in r8s employs a smoothing parameter, which represents how much the assumption of a molecular clock has been relaxed. Cross-validation was run to determine the best smoothing value for the aBS-REL tree (Sanderson, 2003) A latin hypercube sampling scheme (LHC) was used to sample from the aBS-REL parameter distributions so as to estimate the confidence interval, as previously suggested (Wertheim and Kosakovsky Pond, 2011; Wertheim et al., 2013, 2014) 500 samples were drawn from aBS-REL analyses to estimate branch length variance The upper and the lower 95% bounds are used as confidence intervals As a comparison, branch lengths were also estimated using phyML with a maximum-likelihood approach and a GTR+Γ4 model (Guindon et al., 2009) Phylogenetic trees were generated by maximum-likelihood using phyML (Guindon et al., 2010) after codon model selection in HYPHY (Delport et al., 2010) To investigate whether episodic positive selection acted on the internal branches of HCV phylogenies, we applied the branch-site tests from PAML (Zhang et al., 2005) and BUSTED (branch-site unrestricted statistical test for episodic diversification) (Murrell et al., 2015) The p-values from both methods were FDR-corrected to account for multiple tested branches A branch was considered positively selected when statistically significant evidence was obtained with both methods Positively selected sites were then identified through the BEB analysis from model MA (with a posterior probability cutoff of 0.90) (Zhang et al., 2005) and with BUSTED (with a p-value cutoff of 0.05) (Murrell et al., 2015) Sites were called as positively selected if they were detected by both methods BEB and BUSTED were in good general agreement 63.07% of BEB sites were also detected by BUSTED and 65.68% of BUSTED sites were also identified by BEB This metric is preferred over the conventional dN/dS ratio as this latter is rendered to infinite for dS values equal to 0 Although SLAC and FEL use different methodologies to estimate substitution rates (Kosakovsky Pond and Frost, 2005) they yielded very similar results (for all sites in the HCV genome Spearman’s correlation coefficient = 0.73 SLAC and FEL were used to estimate the evolutionary rate at RAV vs The dN-dS statistics was also exploited to provide an overall view of HCV genome evolution only SLAC results are shown (those obtained with FEL were very similar) A total of 127 RAVs in NS3, NS4B, NS5A, and NS5B were included in the study (Supplementary Table S4). RAVs were obtained by merging six recently compiled lists of naturally occurring variants associated with DAA resistance (Rai and Deval, 2011; Bartenschlager et al., 2013; Lontok et al., 2015; Cannalire et al., 2016; Chen et al., 2016; Patino-Galindo et al., 2016) a list of positions where RAVs have been reported was compiled irrespective of the viral genotype carrying the RAV six RAVs that occur at codons pruned from the alignment by GUIDANCE were removed The overall probability of RAV occurrence was calculated over the number of non-pruned codons in NS3 these observations indicate that the binding interaction pose obtained with the two docking methods is reliable The 3D structures were rendered using PyMOL (The PyMOL Molecular Graphics System Host receptors that mediate virus entry often evolve under positive selection (a situation that favors amino acid replacements over silent substitutions) to avoid viral recognition (Sironi et al., 2015) Four cell-surface molecules, CD81, occludin (OCLN), claudin 1 (CLDN1), and scavenger receptor class B member 1 (SRB1), are particularly important for HCV cell entry, although only CD81 and OCLN determine the species-specificity of infection (Bartenschlager et al., 2013; Lindenbach and Rice, 2013) We thus reasoned that if primates experienced long-term interactions with HCV or closely related hepaciviruses signals of positive selection should be detectable at the genes encoding HCV receptors if selection is evident in other mammalian orders these may represent the ancestral HCV reservoirs We retrieved coding sequences of the four genes for mammalian species belonging to different orders, superorders or clades (Supplementary Table S1). Due to the hypothesized role of bats as reservoir hosts for mammalian hepaciviruses, Chiroptera were analyzed separately from other species in the Laurasiatheria superorder. Evidence of positive selection was searched for using models that allow dN/dS to vary among sites in the alignment (Yang, 2007) Likelihood ratio test statistics for models of variable selective pressure among sites Positions involved in HCV binding and/or infectivity are highlighted in yellow both on the structure (circle) and on the protein alignment Positively selected sites Chiroptera are indicated in red LEL: large extracellular loop; SEL: short extracellular loop Positions refer to the human sequence (Accession ID: NM_004356) The observation that the positively selected sites are involved in HCV binding and infectivity suggests that hepaciviruses contributed to shape the genetic diversity of CD81 in bats It is well known that the temporal variation in rates of nucleotide substitutions often results in underestimation of the age of viral lineages (Duchene et al., 2014; Aiewsakun and Katzourakis, 2016). Purifying selection and substitution saturation are strongly associated with temporal rate variation (Duchene et al., 2014) FIGURE 2. tMRCA estimation. (A) Comparison of branch lengths obtained using the aBS-REL and the GTR models for the NS5B abd EHV phylogenies. (B) Timescaled phylogenetic tree estimated for 67 HCV subtypes. The scale bar below the phylogeny represents years before present. The tMRCAs of analyzed nodes are reported in red with 95% confidence intervals. (C) Geographic distribution of HCV endemic transmissions (Simmonds, 2013) Horse-to-human hepaciviral transmission was hypothesized as the origin of HCV (Pfaender et al., 2014; Scheel et al., 2015). EHV isolates show limited divergence and high levels of purifying selection (Simmonds, 2013; Pfaender et al., 2014). We thus used the same approach described above to obtain the tMRCA of extant EHV/CHV strains (Figure 2A) (Supplementary Table S3) producing an estimate of 863 years ago (95% CI: 1726–377) A number of studies have explored the recent selective events that generated intra-genotype and within-host genetic diversity (Jackowiak et al., 2014), whereas the deeper evolutionary history of HCV has remained largely unexplored. We thus used complete sequence information for the 67 recognized HCV subtypes (Smith et al., 2014) to search for selective events that occurred during the radiation of the seven genotypes The structural and non-structural coding regions were analyzed separately, and the core region was excluded due to the presence of a putative alternative reading frame (Xu et al., 2001) Maximum-likelihood phylogenetic trees for E1/E2 region Branch thickness is proportional to the number of positively selected sites Branch lengths are proportional to the number of nucleotide substitutions per site Evidence of episodic positive selection along the internal branches of the phylogenies was searched for using two different branch-site methods, which rely on different assumptions of dN/dS variation among branches (Zhang et al., 2005; Murrell et al., 2015). The two methods provided evidence of positive selection on multiple branches in the structural and non-structural region alignments (Figure 3 A total of 102 sites were found to be targeted by positive selection nine of them selected on more than one branch (Supplementary Table S6) the two positions evolve in concert in the HCV phylogeny with a charged residue always observed at either position 131 or 134 Positively selected sites are colored in red and labeled when located at the NS5B-sphingomyelin binding interface (E) Ligand interaction diagram of best docked pose of NS5B-sphingomyelin Residues within a 6Å distance and hydrogen bonds are shown (see legend) suggesting that HCV adaptation to new hosts does not necessarily entail changes at the direct binding interface with CD81 Recently, a large-scale analysis of patients mostly infected with HCV genotype 3a, identified 30 sites in the viral polyprotein showing association with one or more HLA alleles (Ansari et al., 2017). We found three of these sites (561 in E2, 620 in NS3, and 48 in NS4B) to be positively selected, with site 620 in NS3 (position 1646 in the polyprotein) representing one of the strongest association detected in the study (Ansari et al., 2017) A recent analysis indicated that several RAVs occurred de novo on external branches of HCV phylogenies, although a minority appeared on internal branches, indicating a common origin in multiple strains (Patino-Galindo et al., 2016) the evolutionary history of RAVs has remained a poorly investigated issue (A) Standard box-and-whisker plot representation (thick line: median; box: quartiles; whiskers: 1.5 × interquartile range) of dN-dS (SLAC method) at RAV and non-RAV positions Positively selected RAVs are shown with two flanking amino acid residues for few representative HCV subtypes RAVs are in red depending on the branch they are selected on (B) Plot of dN-dS (SLAC method) across the HCV genome (with the exclusion of the core region) Positively selected sites are denoted with a red dot and RAVs with a blue circle The dashed line represents the median value Positions refer to the H77 strain (AF009606.1) To gain a comprehensive view of the action of selection, we plotted dN-dS along the HCV genome and we superimposed the location of positively selected sites and of RAVS (Figure 6B). In agreement with a previous work that analyzed conservation and selection in HCV-1a and HCV-1b genomes (Patino-Galindo and Gonzalez-Candelas, 2017) dN-dS tended to be higher in the E1 and E2 regions A non-negligible fraction of codons showed almost complete conservation: about 7% displayed dS = 0 and most of these (89%) also had dN = 0 Both RAV positions and positively selected sites displayed variable dN-dS values We note that this is not unexpected for positively selected sites as they were identified using branch-site tests and are thus not selected across the entire HCV phylogeny may date the origin of this virus further back Horse domestication begun around 5000 years ago in Central Asia (Outram et al., 2009): where EHV found to be older close contacts between horses and humans may have resulted in zoonotic cross-species transmission or in the acquisition of HCV and EHV from a common source (possibly bat or rodent) Active sampling of horse and donkeys worldwide will be required to address this important point The time frame of HCV origin and the geographic distribution of the endemic strains are not consistent with the possibility that HCV dispersed with humans following the major out-of-Africa colonization routes across the Old World (65000–45000 years ago) (Nielsen et al., 2017) The dating we estimated for HCV origin instead suggests that the (possible) zoonotic transmission and subsequent spread in human populations occurred in a time-frame when long-distance trade routes were being established The deepest tMRCA for HCV genotypes was obtained for genotype 6 possibly indicating an Asian origin of extant strains Several historical situations may help explain the diffusion of HCV in Asia and Africa Although the present-day distribution of these STIs may not necessarily reflect the historical prevalence of the causative bacteria the hypothesis of STI-facilitated HCV transmission warrants further consideration but the molecular details of the interaction with this virus are unknown we cannot rule out the possibility that pathogens other than hepaciviruses were responsible for the selection signatures we detected at CD81 in bats they provide a proof of principle for the hypothesis that human genetic diversity exerted a selective pressure on HCV and possibly contributed to the radiation of the seven genotypes Clearly, it remains to be evaluated whether changes at positions Y93 and H54 exert their effects via modulation of OAS1 binding, as the docking analysis suggests, at least for position 93. Alternatively, other mechanisms may be at play: a lysine insertion between NS5A positively selected sites K68 and N69, which are not at the binding interface with OAS1, regulates PKR and IRF-3 activity (Pflugheber et al., 2002; Sumpter et al., 2004) In general, the positively selected sites we identified herein represent excellent candidates for future functional studies as they are expected to modulate viral phenotypes. For instance, selected sites in NS5B account for genotype differences in terms of sphingomyelin-driven polymerase activation (Sakamoto et al., 2005; Weng et al., 2010) and the C298I change that arose in the common ancestor of genotypes 1 and 4 may help explain the poor response of these genotypes to IFN therapy that most RAVs investigated here were described for genotype 1 and might confer little or no drug resistance to other HCV genotypes most RAV sites were positively selected on branches different than that leading to genotype 1 Their functional relevance will thus need to be analyzed further RC and CP performed the evolutionary analysis in mammals DF performed the molecular dating analyses and DF performed the evolutionary analysis of HCV phylogenies UP provided support during the bioinformatic analyses The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmicb.2018.00854/full#supplementary-material Association between variants in the interferon lambda 4 locus and substitutions in the hepatitis C virus non-structural protein 5A Accuracy and power of the likelihood ratio test in detecting adaptive molecular evolution doi: 10.1093/oxfordjournals.molbev.a003945 Accuracy and power of Bayes prediction of amino acid sites under positive selection doi: 10.1093/oxfordjournals.molbev.a004152 Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus The molecular and structural basis of advanced antiviral therapy for hepatitis C virus infection Recombination detection under evolutionary scenarios relevant to functional divergence Different domains of CD81 mediate distinct stages of hepatitis C virus pseudoparticle entry Adaptation of hepatitis C virus to mouse CD81 permits infection of mouse cells in the absence of human entry factors Serology-enabled discovery of genetically diverse hepaciviruses in a new host A journey around the medicinal chemistry of hepatitis C virus inhibitors targeting NS4B: from target to preclinical drug candidates Different requirements for scavenger receptor class B type I in hepatitis C virus cell-free versus cell-to-cell transmission Sexually acquired hepatitis C virus infection: a review Global prevalence of pre-existing HCV variants resistant to direct-acting antiviral agents (DAAs): mining the GenBank HCV genome data ClusPro: a fully automated algorithm for protein-protein docking Highly divergent hepaciviruses from African cattle Distinct patterns of natural selection in the reverse transcriptase gene of HIV-1 in the presence and absence of antiretroviral therapy CodonTest: modeling amino acid substitution preferences in coding sequences The impact of hepatitis C virus entry on viral tropism Infectious diseased and human population history CrossRef Full Text | Google Scholar Structural basis for cytosolic double-stranded RNA surveillance by human oligoadenylate synthetase 1 Evidence for novel hepaciviruses in rodents Mutagenesis of a conserved fusion peptide-like motif and membrane-proximal heptad-repeat region of hepatitis C virus glycoprotein E1 Identification of the hepatitis C virus E2 glycoprotein binding site on the large extracellular loop of CD81 The performance of the date-randomization test in phylogenetic analyses of time-structured virus data Analyses of evolutionary dynamics in viruses are hindered by a time-dependent bias in rate estimates Diverse CD81 proteins support hepatitis C virus infection Molecular evolution of human coronavirus genomes Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes Control of PKR protein kinase by hepatitis C virus nonstructural 5A protein: molecular mechanisms of kinase regulation Identification of a novel determinant for membrane association in hepatitis C virus nonstructural protein 4B Estimating maximum likelihood phylogenies with PhyML New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0 OPLS3: a force field providing broad coverage of drug-like small molecules and proteins Dual function of CD81 in influenza virus uncoating and budding Time-dependent estimates of molecular evolutionary rates: evidence and causes Coastal connectivity: long-term trading networks across the South China Sea CrossRef Full Text | Google Scholar Phylogeny and molecular evolution of the hepatitis C virus Characterization of a canine homolog of hepatitis C virus Identification of rodent homologs of hepatitis C virus and pegiviruses Kosakovsky Pond Not so different after all: a comparison of methods for detecting amino acid sites under selection Kosakovsky Pond Automated phylogenetic detection of recombination using a genetic algorithm The ClusPro web server for protein-protein docking Determinants for membrane association of the hepatitis C virus NS2 protease domain Identification of conserved residues in hepatitis C virus envelope glycoprotein E2 that modulate virus dependence on CD81 and SRB1 entry factors PubMed Abstract | CrossRef Full Text | Google Scholar Origin of hepatitis C virus genotype 3 in Africa as estimated through an evolutionary analysis of the full-length genomes of nine subtypes Mutagenesis of the fusion peptide-like domain of hepatitis C virus E1 glycoprotein: involvement in cell fusion and virus entry The ins and outs of hepatitis C virus entry and assembly The evolution and genetics of virus host shifts Hepatitis C virus drug resistance-associated substitutions: state of the art summary An algorithm for progressive multiple alignment of sequences with insertions Full-length genomes of 16 hepatitis C virus genotype 1 isolates representing subtypes 1c and four unclassified variants reveal ancestral relationships among subtypes RDP: detection of recombination amongst aligned sequences Detecting and analyzing genetic recombination using RDP4 Global distribution and prevalence of hepatitis C virus genotypes Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence The effect of genetic structure on molecular dating and tests for temporal signal Gene-wide identification of episodic selection Detecting individual sites subject to episodic diversifying selection A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates with application to the chloroplast genome Tracing the peopling of the world through genomics IFN-lambda4: the paradoxical new member of the interferon lambda family Comparative analysis of variation and selection in the HCV genome Comprehensive screening for naturally occurring hepatitis C virus resistance to direct-acting antivirals in the NS3 and NS5B genes in worldwide isolates of viral genotypes 1 to 6 Protein synthesis and endoplasmic reticulum stress can be modulated by the hepatitis C virus envelope protein E2 through the eukaryotic initiation factor 2alpha kinase PERK Google Scholar Interferon lambda 4 variant rs12979860 is not associated with RAV NS5A Y93H in hepatitis C virus genotype 3a Interferon lambda 4 genotypes and resistance-associated variants in patients infected with hepatitis C virus genotypes 1 and 3 Response of hepatitis C virus to long-term passage in the presence of alpha interferon: multiple mutations and a common phenotype Natural reservoirs for homologs of hepatitis C virus Regulation of PKR and IRF-1 during hepatitis C virus RNA replication Evaluation of methods for detecting recombination from DNA sequences: computer simulations Improving the performance of positive selection inference by filtering unreliable alignment regions The epidemic behavior of the hepatitis C virus Investigating the endemic transmission of the hepatitis C virus Hepacivirus cross-species transmission and the origins of the hepatitis C virus Bats are a major natural reservoir for hepaciviruses and pegiviruses New opportunities in anti-hepatitis C virus drug discovery: targeting NS4B PubMed Abstract | Google Scholar PubMed Abstract | CrossRef Full Text | Google Scholar Mutational analysis of the hepatitis C virus E1 glycoprotein in retroviral pseudoparticles and cell-culture-derived H77/JFH1 chimeric infectious virus particles Host sphingolipid biosynthesis as a target for hepatitis C virus therapy R8s: inferring absolute rates of molecular evolution and divergence times in the absence of a molecular clock Statistical tests for detecting gene conversion Google Scholar High diversity of West African bat malaria parasites and a tight link with rodent Plasmodium taxa Surveying the global virome: identification and characterization of HCV-related animal hepaciviruses Schneidman-Duhovny PatchDock and SymmDock: servers for rigid and symmetric docking GUIDANCE2: accurate detection of unreliable alignment regions accounting for the uncertainty of multiple parameters Global epidemiology of hepatitis C virus infection CrossRef Full Text | Google Scholar Novel procedure for modeling ligand/receptor induced fit effects Hepatocyte CD81 is required for Plasmodium falciparum and Plasmodium yoelii sporozoite infectivity Evolutionary insights into host-pathogen interactions from mammalian sequence data Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource Less is more: an adaptive branch-site random effects model for efficient detection of episodic diversifying selection Viral evolution and interferon resistance of hepatitis C virus RNA replication in a cell culture model Hepatitis C virus NS5A protein interacts with 2’,5’-oligoadenylate synthetase and inhibits antiviral activity of IFN in an IFN sensitivity-determining region-independent manner Hepatitis C virus NS4B targets lipid droplets through hydrophobic residues in the amphipathic helices Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein CrossRef Full Text | Google Scholar Tellinghuisen Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase Detection and characterization of homologues of human hepatitis viruses and pegiviruses in rodents and bats in Vietnam Differential infection patterns and recent evolutionary origins of equine hepaciviruses in donkeys Sphingomyelin activates hepatitis C virus RNA polymerase in a genotype-specific manner RevTrans: multiple alignment of coding DNA from aligned amino acid sequences A case for the ancient origin of coronaviruses Purifying selection can obscure the ancient age of viral lineages Evolutionary origins of human herpes simplex viruses 1 and 2 Manifestations and management of lymphogranuloma venereum Synthesis of a novel hepatitis C virus protein by ribosomal frameshift Hepatocyte permissiveness to Plasmodium infection is conveyed by a short and structurally conserved region of the CD81 large extracellular domain PAML 4: phylogenetic analysis by maximum likelihood Bayes empirical Bayes inference of amino acid sites under positive selection Evaluation of an improved branch-site likelihood method for detecting positive selection at the molecular level A library of infectious hepatitis C viruses with engineered mutations in the E2 gene reveals growth-adaptive mutations that modulate interactions with scavenger receptor class B type I Clerici M and Sironi M (2018) Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV Copyright © 2018 Forni, Cagliani, Pontremoli, Pozzoli, Vertemara, De Gioia, Clerici and Sironi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) distribution or reproduction in other forums is permitted provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: Manuela Sironi, bWFudWVsYS5zaXJvbmlAYnAubG5mLml0 Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish IES PISA – The quintet of Paolo Campani, ninth in the standings and already safe, is finishing the season in good shape, as demonstrated in the narrow defeat in Livorno, on the field of the second-placed Chimenti. On Thursday the Biancoceleste quintet faces yet another play-off contender, Dinamo Rosignano, with the intention of closing the championship in the best possible way. most of which are in the very Museum of Stele Statues the only museum dedicated to these sacred objects) and finding one is not an everyday matter.The head in question dates back to the Copper Age (about 5,000 years ago) according to museum director Angelo Ghiretti It has the classic half-moon shape typical of the statues of group “B” (one of the three groups into which the stelae are divided: those with the crescent-shaped head detached from the torso are and the stylized earrings she wears near her eyes unquestionably reveal her gender which entered the catalog of stelae statues under the name “Pontremoli Monte Galletto 85” (each stelae statue is named after the site where it was found) details of workmanship were found on the surface of the piece that could not be reproduced by a contemporary craftsman: in particular the head shows obvious signs of wear resulting from the use of the technique of bushhammering with tenacious pebbles This was the method of workmanship by which stelae statues were made which were not produced with metal tools but with very hard and resistant stones which left marks on the surface that would later wear away due to the multi-millennial action of weathering The surface of the head was then also found to have some nicks from plowing with plows and mechanical hoes (the head was found fortuitously in a plowed field) The head went to enrich the collection of the Museum of Stele Statues on the occasion of the European Archaeology Days of June 18-19-20 organized in Italy by the Ministry of Culture - Directorate General for Museums: the six new finds were presented to the public and scholars on Saturday and as of the latter date they can be seen in the museum already in a condition of progressive deterioration due to weathering were removed from the outdoor environment and integrated into the museum itinerary and with the support of Rotary Club Lunigiana it was possible to replace the originals with identical outdoor casts the deposit of the Levanto stele head fragment was granted to the Museum of Lunigiana Stele Statues which was willing to provide copies to both the Archaeological Museum of La Spezia and the Permanent Exhibition of Material Culture in Levanto Along with the Levanto head will be exhibited indicates the geographical limits of distribution of the stele statues: the fragment from Levanto the maximum western limit the eighteenth-century gargoyle recently found at Piagnaro Castle and a singular sexed guardian fac iòn (the “faciòn,” i.e. “big face,” is an ancient apotropaic head typical of the folk art of Val di Vara and Val di Magra) recovered fifty years ago in the Rossano-Zeri valley purchased and donated to the Museum by director Angelo Ghiretti The facións’ connection with stelae lies in the fact that when heads of stelae statues were found they were sometimes reused on portals (Aulla-Calamazza) or in their immediate vicinity (Caprio) just as with the facións of the Lunigiana folk tradition Pictured is the Pontremoli Monte Galletto 85 I had no idea of how beautiful Pontremoli is Last night’s visit and this morning’s public greetings with the mayor surprised me – I really want to recommend having a tour of the town before leaving the Appennini mountains you leave the mountain chain behind you and enter the Lunigiana valley but quite overshadowed: surrounded by the Appennini mountains and by the famous Tuscan landscapes that we see in pictures and postcards Lunigiana tends to remain undervalued compared to its potential as a tourism destination dialects and gastronomy: another face of a vast and various region which should not identify in few popular locations and traditions I highly recommend a visit to explore such a hidden beauty Mayor of Pontremoli Lucia Baracchini is a charismatic and an inspiring example for women working in politics: I very much enjoyed speaking with her We walked together for a few kilometers and arrived in Filattiera where Lucia handed over the pilgrim’s stick to mayor Annalisa Folloni gave it to the mayor of Aulla – today the stick was handed over from mayor to mayor for the entire stage we crossed smaller picturesque villages (in Italian Many of these towns have been bombed during Second World War and reconstructed maintaining their original medieval aesthetics In none of these villages did we found a single tourist that has recently been restructured and transformed into a hostel which will open in March 2022 – what good news and important development for the increasing passage of pilgrims in this valley Today we were surrounded by an ocean of vineyards in the valley below the mountains where many rivers converge We soon arrived to the impressive Pieve di Sorano a parish church from the early Middle Ages and then stopped both in Filattiera and in Licciana Nardi for a refreshing break and to get our credentials stamped In Licciana Nardi we visited the Castle of Malaspina which is currently holding an exhibition about Dante Alighieri It seems that Dante got lost in a forest close by and took inspiration from it for the ‘Selva Oscura’ the Dark Forest in which he gets lost at the beginning of the Divine Comedy Tomorrow we walk into the region of Liguria – but it won’t be long before we return to Tuscan territory These almost-two Ligurian stages give us a chance to peek in this amazing land where mountains meet the Mediterranean Sea – Surprisingly beautiful town of Pontremoli and great talk with mayor Lucia Baracchini – Discovering the new pilgrim’s hostel in Canale inside a medieval tower – The Castle of Malaspina in Licciana Nardi and learning the true story of Dante Alighieri Group of local walkers from CAI Filattiera The week that has opened is very important for Pontremoli which after the reconfirmations has seen the transfer man Cocchi, busy in closing the negotiations with the midfielder Michele Moscatelli, and with the striker Sebastiano Ginesi with lightning operations. Edouard Schumacher (LS Group) becomes the official representative of the Dallara brand an ingenious alchemy of poetry and automotive design is born It was during an evening in mid-February that LS Group wanted to pay a retrofuturistic tribute to the car reinforcing the unique emotional bond it has always maintained with each of us the evening was orchestrated like an Italian love story who unveiled extraordinary vehicles to around a hundred distinguished clients and the media The event was held in a confidential location in Paris where Edouard Schumacher received all his guests « We have always believed in the men and women who make the cars of yesterday and tomorrow This meeting with the Dallara family inspired us to pay tribute to the love of automobiles as a vehicle for inspiration and sharing among enthusiasts It is our duty to remember the genius of a man who infused motorsport into the entire industry and whom we want to support in France. » The Dallara brand was born over half a century ago a talented graduate of the prestigious Politecnico di Milano who made his debut with Enzo Ferrari in the 1960s he joined some of the finest Italian brands eventually designing the Lamborghini Miura this inspiration ultimately led to the creation of a new car brand in his own workshops in 1972 He subsequently developed chassis for several renowned manufacturers and produced chassis for racing cars Giampaolo Dallara has accumulated unique expertise in performance worldwide with the secret of selecting noble materials for a noble passion « Our goal is to design and produce the fastest and safest cars in the world The partnership with the LS Group distribution family is a pivotal moment for Dallara in reaching out to the French public. » Explain Giampaolo Dallara and Andrea Pontremoli The Schumacher Group is a French automobile distributor founded in Paris in 1947 the family business joined the LS Group (Lamirault-Schumacher Group) while continuing to develop an independent division of Sport and Prestige Brands under the EF SCHUMACHER brand It is first and foremost a story of men and a friendship between Edouard Schumacher The complementary nature of their brands and regions was a key asset of the two former groups and their merger created a coherent geographic coverage and strong synergies LS Group's 63 dealerships are spread across five regions in France: Île-de-France The generalist brands that historically formed Lamirault-Schumacher's base are divided into three divisions: Groupe Renault LS GROUP has expanded into the Grand Ouest region under the Volvo brand Edouard Schumacher has created a sports division that includes brands such as Alpine 32 used cars and carries out 000 after-sales operations each year the brand makes extensive use of this preferred material the chassis of world-famous cars have raced on these carbon fiber chassis The best expertise in automotive engineering three versions of the Dallara Stradale were presented: a Racing cockpit Coupé version with two gullwing doors a Roadster version with a polycarbonate windshield a Barchetta version for those always looking for higher performance as well as two racing cars produced by Dallara: the Cadillac Dpi a car in the Daytona Prototype International category and sometimes accepts failure but always shares knowledge and overcomes difficulties with resilience... The greatest danger is believing you know " The company believes in keeping one's word and the seriousness of human relationships and a love of knowledge. Knowing how to question what exists in adaptable and new ways magazine lifestyle dedicated to the worlds of luxury Find Luxe Infinity Magazine on reading platforms Here you can see the webcast of the BMW Group Press Conference at the Auto Shanghai 2025 Task of understanding “DNA” of different LMDh brands has been “very interesting” for Dallara… Dallara CEO Andrea Pontremoli says that ‘understanding the DNA’ of Cadillac and BMW has been key in the company’s work developing two stylistically different LMDh cars Cadillac and BMW last month revealed the designs of their respective top-category prototypes that have been built on the Dallara spine and are due to debut next year While the Cadillac ‘Project GTP Hypercar’ was presented in high-resolution renders the General Motors brand has expressed that these are “pretty close” to the final look The BMW M V8 Hybrid The two vehicles appeared extremely different despite being developed on the same Dallara base chassis Pontremoli said that the “beauty” of the LMDh platform which is now being viewed in terms of produced and running cars is that it has required Dallara to closely understand the wishes of each manufacturer to enable those branding differences to stand out Dallara has already worked with Cadillac in this way on the American brand’s DPi car however BMW is entering prototypes for the first time in more than two decades “We are almost at the same level on the two cars and I think we have cars that are almost ready,” Pontremoli told Sportscar365 we will see the two cars on the racetrack to test “It’s a very interesting project because our job is not only to produce a car that is competitive on the racetrack It’s also to try to understand the DNA of the brand and to transfer this onto the car “We have the stylists from Cadillac and BMW working here in two different departments working with our aerodynamic people to try to accommodate the performance and style of the car you cannot believe they come from the same spine but they are both competitive with these very different styles and shapes “The beauty of our job is that we can build up the DNA of our customers to try to transfer to the fans the real DNA of their brand It is interesting and I am looking forward to seeing these cars on the racetrack very soon.” Pontremoli explained that Dallara has needed to closely understand each manufacturer’s ethos so that Cadillac and BMW can access the potential marketing value of LMDh which is valid in the FIA World Endurance Championship and the IMSA WeatherTech SportsCar Championship Cadillac is racing in both series while BMW is set for IMSA only next year “It is an enormous marketing tool where you can explain to the world which kind of innovation you have in your brand,” Pontremoli said “This is why it’s important for us to interpret and understand the DNA of the brand and try to have a car that represents this DNA but they are different in terms of expression on what they want to represent “It’s why I think endurance [racing] is closer to the real-life world “Because when you see the new Cadillac or the new BMW you can see styling points that you can also see on your everyday car.” Dallara received “several requests” from other brands wanting to use its chassis as the base for an LMDh car but the company is currently reluctant to expand beyond its two customers “I don’t want to work on quantity but I want to work on quality,” he said “So I want to assure our customers that we are doing the right things in the right way So I’m not following the money or business on this we will stay there [with two manufacturers] It is something that we have to look forward to in 2024 As it focuses on supporting Cadillac and BMW in LMDh, Dallara is also busy working with NASCAR and Hendrick Motorsports to modify a Next Gen Chevrolet Camaro ZL1 that will enter next year’s 24 Hours of Le Mans as an experimental Garage 56 entry “We have been involved to adapt this car for this kind of different [renewable] fuel,” Pontremoli said “We have some small changes from the actual car I think that they will announce what they want to do “We are doing simulation to understand the performance of the car at Le Mans but we are working to have something that is a good compromise.” Daniel Lloyd is a UK-based reporter for Sportscar365 covering the FIA World Endurance Championship Fanatec GT World Challenge Europe powered by AWS and the IMSA WeatherTech SportsCar Championship A look into the life of AWA tire specialist (and baking pro) Ashley Baily.. Bobby Rahal on improvements to BMW Team RLL's execution after recent misses.. Porsche pegged back in latest revision of IMSA's Balance of Performance.. Alec Udell confirmed as Robert Wickens' co-driver in No suffice it to say that in the last ten years there have been only four finds And always by chance: usually by hikers walking in the woods or The discovery of the Zignago stele caused quite a stir because no one had ever seen such an object an inscription in Etruscan characters (“MEZUNEMUNIUS,” a word whose meaning is still unknown today) had been added to the sculpture had led scholars of the time to believe it was an Etruscan artifact We have no written documents that can help us in the task of establishing the dating of the found statues so it is necessary to rely only on the archaeological contexts and stratigraphies or on the objects that are sometimes depicted in the stelae statues.Thus it is possible to establish that the stelae statues were produced along a time span from the beginning of theEneolithic with most of the statues being in the middle of theCopper Age (between 2800 and 2300 B.C.C.) The finds have occurred in a restricted area: almost all in the Magra River basin in historic Lunigiana although stele statues have also been found in the mountains The few stele statues outside the Val di Magra include those found in Lerici and La Spezia the Zignago stele itself (the only one found in the Val di Vara) and a small group of statues found in Minucciano the last village in Lunigiana before Garfagnana The stele statues were found mostly distributed in a few places: in the Selva di Filetto a wonderful chestnut forest that in ancient times was a sacred place of the Apuan Ligurians the people who inhabited these places (and who probably used the Selva for religious rites and ceremonies) as many as eleven stele statues were found Nine statues come instead from Pontevecchio and in the place where they were originally erected (in order of progressive height) if rare are the findings of statues tout court very rare and exceptional are those of statues in situ (the ones we know of were in fact almost all found out of their context) interesting answers about their function might come from the latter While it is indeed true that the modern history of stele statues begins in 1827 it can hardly be said that no one had seen the ancient statues of Lunigiana before this date To understand why most of the stele statues were found out of their original context it is necessary to start from another date: 658 the year in which the Council of Nantes was held during which a direct order was issued against the “lapides” worshipped in the woods it is decreed that all menhirs and in general ancient devotional stone statues be buried and that Christian temples be erected over these pits “It cannot be a coincidence,” wrote archaeologist Roberta Iardella “that many Christian places of worship (churches shrines or cemeteries) have arisen on or near sites where stele statues have been found or that these have been reused for the construction of the buildings themselves even with different intentions.” The cult of stelae statues endured even after the fall of the Roman Empire: this is well attested by an epitaph from the year 752 found in the church of San Giorgio in Filattiera in which the praises of a certain Leodgard (perhaps a bishop of Luni named Leodegario) are woven who “gentilium varia hic idola fregit” and “delinquentium convertit carmina fide,” or “destroyed the idols of the pagans and converted sinners.” This plaque has been read as a praise of a physical action on Leodegarius’ part: having materially destroyed the idols of the pagans of Lunigiana and having converted their worshippers to the Christian faith “It follows that stele statues,” Stefano Di Meo has written “still in the 8th century CE were seen by the official Christian world as potentially dangerous and therefore capable of hindering the process of Christianization.” many stele statues have been found near Christian shrines (such as the three statues in Minucciano) and others have been reused instead: this is the case of the Talavorno stele statue one of the most recent finds (dating back to 2007) which was reused as a step in the altar of the monastery of St a building already ruined in the 16th century of the Sorano VII statue (the stele statues are identified with the name of the place of discovery found in 2003 in the locality of Quartareccia and used as a slab in a Ligurian-Roman box tomb of the 2nd-1st century BC the Lerici stele was used as a parapet for a well was even used as a memorial plaque in the village church to commemorate some work that followed in 1779 (it had been bricked into the bell tower) there are the stele statues used simply as building material and in this sense the cases are many: one can mention for example the one in Codiponte Scholars have been debating for decades what the function of stele statues was most of these sculptures have been found out of their context There is no extensive archaeological record of the necropolises at the site although useful information could be gleaned from the few known burials We know virtually nothing about the settlements in the area And about the ancient inhabitants of these lands metalworking and little trade with neighboring peoples The first scholar to deal in depth with the stele statues was the La Spezia historian and journalist Ubaldo Mazzini (La Spezia the first director of the Biblioteca Civica della Spezia (which is now named after him): in 1908 studying the ancient sculptures of Lunigiana and believing them to be the product of the people of Celtic origin who inhabited these lands he came to the conclusion that they must have been funerary monuments this assumption has been better contextualized and it is believed to be valid especially for the more recent statues there are three groups into which the stele statues are classified: A sculptures that are much more realistic than the older stelae and probably animated by the desire to make a portrait of the deceased again in Etruscan characters (one is the aforementioned stele of Zignago one of the most famous because it is among the most conspicuous and the stele of Filetto II): it is not clear what the inscriptions referred to but it is likely that they were names of persons we need to consider the historical context in which they were made: this is the era during which copper processing began to take hold an activity that made it necessary to search for deposits and market the products Thus a decidedly different model of life was established than the previous one experienced an impulse toward a lifestyle based on farming would transform the Apuan Ligurians into decidedly warlike populations And it is precisely this lifestyle that is probably at the origin of the use of stelae statues as a method of marking routes are in any case concentrated in areas that have specific environmental characteristics: usually along important connecting areas and communication routes the hypothesis that the stele statues served as landmarks to be placed near travel routes population centers or areas that had considerable commercial importance depicting deities or great ancestors who were placed in these places for their protection All the stele statues found are made of sandstone a stone found in abundance in the Magra valley in the form of blocks: portions were detached rough-hewn to make the block part reach the desired shape and then worked in bas-relief to execute body parts for example) were made with rudimentary drills which were rotated on themselves while holding them in the hands the sculptors smoothed the whole thing with sand and in this they differ from other productions of prehistoric sculpture such as menhirs were not intended to resemble the figure of a human being the one that includes the oldest statues; Group B which at the present state of knowledge is the thickest; and Group C that of the most recent and realistic statues There is also a group of statues that have survived in too fragmentary a manner to fit into one of the three subgroups The statues of Group A are distinguished by the semicircle-shaped head attached to the body in relation to which it knows no solution of continuity (only a line at shoulder height is meant to represent separation in a stylized way) the arms and hands are represented in a very basic form on the central block that forms the body even in the earliest statues it is possible to recognize male and female statues: the latter found in 1910 and one of the best-preserved presents the unmistakable breast suggested with two sphere-shaped reliefs on the chest The male statues obviously do not present themselves with this element but are sometimes accompanied by objects such as the Sorano VII stele or like the Casola stele The female stele statues have been interpreted by Pia Laviosa Zambiotti as sculptures dedicated to the cult of fertility where the breasts can be identified as an attribute of motherhood (none of the statues which account for roughly a quarter of the total number of stelae found are presented with the depiction of sexual organs) The second group is probably the best known that of the stele statues most commonly associated with the collective imagination: these are the statues with half-moon-shaped heads divided from the rest of the body by an often stout neck (see and so are the objects (in the Canossa I stele we note a dagger with the pommel also shaped like a half-moon and the blade inserted in a ribbed scabbard) breasts also appear in female statues (in those of Falcinello and Treschietto we can also see nipples) which lacks a head but in which we can still make out a ringed goliath In some statues (such as Philetus VIII or the one discovered in 2021 at Monte Galletto) holes can be seen on either side of the eyes: it is still unclear whether these are ears or earrings where the human figure is made with more realistic features They are also characterized by workmanship that for some details (such as the head arms and legs are carved in relief and assume less stereotypical poses The head is round in shape and is often well defined which is the best known of the statues in this group This sculpture also has ears worked in relief more realistically than the clavicular line of the group A and B statues The Bigliolo stele moreover also features a belt some ancient statues were later reworked in later periods: this is the case with the Lerici stele carved in the late Iron Age (6th century B.C.) on an ancient stele from Group A today most of these ancient prehistoric sculptures are preserved at the Museum of Stele Statues at the Piagnaro Castle in Pontremoli the institute to visit if you want to have a good knowledge of stele statues since the sampler kept here offers a complete representation of everything we know about these works and in addition it allows you to see them displayed side by side with various objects found in the contexts of their discovery or in any case traceable to the uses of the Apuan Ligurians It is due to Augusto Cesare Ambrosi (Casola in Lunigiana one of the foremost experts on stele statues and author of numerous publications on the subject which has been housed in the castle since 1975 and is the heir to the first collection put together by Ambrosi between the 1950s and 1960s in the town hall of Casola in Lunigiana The museum in Pontremoli was renovated with a new layout in 2015 which provided the itinerary with new panels and new evocative lighting to better enhance these ancient sculptures plus the museum was also equipped with elevators that connect the castle to Pontremoli’s historic center Other statues are preserved in various museums: this is the case with some stelae such as the Zignago stele (which was the first to be found and is at the Museum of Ligurian Archaeology in Genoa) the Moncigoli I (kept at the National Archaeological Museum in Florence) the Fosdinovo stele (at the Castle of Castiglione del Terziere near Bagnone) several statues found in the Selva di Filetto (which are at the Museo Civico della Spezia) one of the most important of group C (kept at the Museo del Territorio dell’Alta Valle dell’Aulella in Casola in Lunigiana) is instead walled in the courtyard of Palazzo Bocconi in Pontremoli A special case is that of the Canossa II stele found in 1976 in the woods between Lusuolo and Canossa It is therefore necessary to travel to Lunigiana to discover the fascination of these extraordinary sculptures: as Augusto Cesare Ambrosi wrote “they are the surviving traces of a great religion that as the Stone Age passed and the great invention that was metals spread transformed stone into an object of worship into a sign of perennial memory capable of overcoming and conquering time.” As for the identification it matters little according to Ambrosi: more important is their function: “Whether they are real deities or just emerging figures who were wanted to be remembered and commemorated were certainly monuments in which a charge of affection and love was transfused must have flowed into that heated sentiment we now call idolatry.” Witnesses of a very distant past stele statues today preserve the memory of the ancient peoples who inhabited the Lunigiana and who Positive news for the Via Francigena and slow tourism comes from the approval of the 2024 budget law by the Italian government With reference to the revitalisation and tourist promotion of the ‘religious pilgrimage routes’ the fund for the infrastructure of the ‘walking routes system’ in Italy has been refinanced for 2024 it will be possible to fund many projects that were admitted in the Italian Ministry of Tourism’s recent call for proposals The Jubilee of 2025 is also at the core of the manoeuvre: a fund of 75 million euro in the year 2024 305 million euro in the year 2025 and 8 million euro in the year 2026 for the planning and implementation of works and interventions functional to the event has been established Share this articleand follow us on social media: 👉🏻 Itinerary 👉🏻 Where to sleep 👉🏻 I ❤️ Francigena 👉🏻 The Via by bicycle 👉🏻 Events Calendar The European Association of the Via Francigena unites municipalities and countries crossed by the Via Francigena We’re always on the lookout for new partners who share our values and who want to help us promote sustainable travel across Europe EAVF General Assembly, Pavia (Italy)  |  20 October 2023 Volume 7 - 2020 | https://doi.org/10.3389/fmats.2020.601645 This article is part of the Research TopicBioceramics and/or Bioactive Glass-based CompositesView all 7 articles Biodegradable composite materials represent one of the major areas of investigation for bone tissue engineering due to their tuneable compositional and mechanical properties which can potentially mimic those of bone and potentially avoid the removal of implants mitigating the risks for the patient and reducing the overall clinical costs the introduction of additive manufacturing technologies enables a strict control over the final morphological features of the scaffolds the optimisation of 3D printable resorbable composites made of biocompatible polymers and osteoinductive inorganic phases offers the potential to produce a chemically and structurally biomimetic implant The present work focuses on the development and process optimisation of two hybrid composite filaments to be used as feedstock for the fused filament fabrication 3D printing process A Poly L-lactic acid matrix was blended with either rod-like nano-hydroxyapatite (nano-HA) or nanoparticles of mesoporous bioactive glasses both partially substituted with strontium (Sr2+) due to the well-known pro-osteogenic effect of this ion Both inorganic phases were incorporated into Poly L-lactic acid using an innovative combination of processes obtaining a homogeneous distribution throughout the polymer whilst preserving their ability to release Sr2+ The filament mechanical properties were not hindered after the incorporation of the inorganic phases resulting in tensile strengths and moduli within the range of cancellous bone 50 ± 10 MPa and 3 ± 1 GPa the rheological characterization of the hybrid composites indicated a shear thinning behaviour ideal for the processing with fused filament fabrication proving the potential of these materials to be processed into 3D structures aiming bone regeneration this FDA approved polymer is biodegradable The previous examples underline the wide interest of the scientific community active in the field of bone regeneration towards composite systems based on bioactive micro and nanoparticles in order to stimulate bone reforming ability In this respect, the aim of this study is to produce a bioactive hybrid composite with mechanical properties similar to native bone, able to provide a sustained release of osteogenic ions as a measure of treatment, and suitable for the design of scaffolds by means of AM technologies (Navarro et al., 2008) Sr-substituted MBGs and nano-HA were synthesised and fully characterised with focus on their morphology and Sr2+ release kinetics and then used to produce the hybrid composites by soaking the polymer granules into a pre-formed aqueous-based paste dispersing the inorganic phases The resulting hybrid formulations were then easily inserted into an extruder and processed to produce a consistent filament The proposed approach is novel and allowed a straightforward incorporation of the inorganic phase into the polymeric matrix without requiring toxic or flammable chemicals the extrusion of the obtained hybrid systems allowed the homogeneous dispersion of the inorganic phase within the PLLA matrix The extruded filaments were characterized in terms of morphological PLLA granules (Purasorb PL 38) with average density of 1.24 g/cm3 were obtained from Corbion (Purac Biomaterials) The Sr2+ substituted nano-HA (HA_50%Sr) was obtained from FLUIDINOVA (Maia The MBGs were synthesised by the authors as described in next section MBG nanoparticles containing strontium (MBG_SG_10%Sr) were synthesized via a sol-gel route (molar ratio Sr/Ca/Si = 10/5/85), based on a modified procedure reported by Wu et al. (2012) The protocol implies the preparation of two solutions that are later combined solution A consisted of 25 ml of NH4OH (ammonium hydroxide solution Italy) mixed with 140 ml of ethanol (EtOH) 12 g of cetilmethylammoium bromide (CTAB were added to the solution and left to fully dissolve under stirring Solution B was obtained by dissolving 9.4 g of tetraethyl orthosilicate (TEOS Solution A was added to solution B and stirred for 20 min Then 0.94 g of calcium nitrate tetrahydrate (Ca(NO3)2·4H2O Italy) and 1.67 g of strontium nitrate (Sr(NO3)2 Italy) were added and stirred for 10 min 4.7 g of TEOS were added and stirred for 5 h The solution was centrifuged at 10,000 rpm for 3 min (Hermle Labortechnik Z326 This powder was washed three times with water The final precipitate was dried overnight at 70°C the powder was calcined at 600°C in air for 5 h (heating ramp 1°C/min The production of the composite filaments was based on two successive steps. Firstly, aqueous suspensions containing the inorganic phases were made, then combined with PLLA granules to promote a homogeneous mixing of both materials. The obtained mixture was then extruded using a twin-screw extruder to produce the filaments (Figure 1) FIGURE 1. Schematic representation of the process for the production of composite filaments containing MBG_SG_10%Sr (Melo, 2019) The same process was used for the filaments containing HA_50%Sr except for the preparation of the related suspension (provided by FLUIDINOVA) In-house suspensions were produced by dispersing the powders of each inorganic phase in water at a 15 wt% concentration The suspension was stirred for 20 min at room temperature at 300 rpm until completely homogeneous The incorporation of the inorganic phases into the polymer matrix was attained by contacting PLLA granules with the produced suspensions containing a percentage of inorganic phase of 5 wt% for HA_50%Sr and 2 wt% for MBG_SG_10%Sr The obtained soaked granules were distributed on weighing boats covered with pierced aluminium foil and placed under vacuum in a desiccator until complete water evaporation was achieved Every 12 h the granules were removed from vacuum and manually stirred with a spatula to guarantee the homogeneous pellet coverage To ensure the removal of the possible remaining moisture the granules were dried overnight in an oven at 50°C pelletized and re-extruded to promote the inorganic phase distribution The temperatures defined for the first extrusion process were 125/240/240/220/180°C The extruded material was inserted in a haul-off machine and pulled at 1.0 mm/s for a feed speed of 15 ± 2 rpm and extrusion speed of 40 ± 10 rpm The composite filaments were pelletized using a Rondol pelletizer and re-extruded with the following temperatures 125/200/200/180/160 C for a hopper feed speed of 17 ± 1 rpm and the extrusion speed of 19 ± 1 rpm A single extrusion was applied to produce PLLA filaments The morphology of the MBG_SG_10%Sr and HA_50%Sr particles was studied with Field-Emission Scanning Electron Microscopy (FE-SEM) using a ZEISS MERLIN instrument (Oberkochen 10 mg of powder were dispersed in 3 ml of isopropanol and sonicated using an ultrasonic bath (Digitec DT 103H Bandelin) for 10 min to obtain a stable suspension A drop of the suspension was deposited on a copper grid (3.05 mm Diam.200 MESH left at room temperature to evaporate the isopropanol and subsequently a chromium layer was sputtered to enhance the sample conductivity The effective presence of Sr2+ within the inorganic phase particles was investigated by means of Energy Dispersive X-Ray Spectroscopy (EDS) using the ZEISS MERLIN Instrument for the MBG_SG_10%Sr and a scanning electron microscopy (SEM) (Desktop SEM Phenom XL The particle’s specific surface area (SSA) was measured by applying the Brunaeur while the Density Functional Theory (DFT) method using the NLDFT kernel of equilibrium isotherms was applied to calculate the pore size distribution the sample was degassed at 150°C for 3 h Nitrogen adsorption-desorption isotherms were measured at the temperature of -196°C (ASAP2020 X-ray diffraction (XRD) measurements (X’Pert PRO Netherlands) were conducted only on HA_50%Sr samples exposing the powders to a CuKα radiation imposing a current of 40 mA and a voltage of 40 mV The analysed two theta (2θ) angles were between 10 and 80° with a step size of 0.013 2θ degrees and a scan step time of 45 s XRD spectrum analysis for phase identification was performed through the X’Pert HighScore software The hybrid composite filament characterization provided results about the inorganic phase distribution within the polymeric matrix as well as their mechanical and rheological properties filaments were cut into 4 ± 1 mm pieces and placed over an aluminium stub The samples were coated with a 7 nm chromium layer and the images were acquired using the Desktop SEM Phenom XL (Phenom-World B.V. Netherlands) at an accelerating voltage of 10 kV The presence of strontium ions was detected by EDS filaments (n = 3) underwent tensile testing The displacement-controlled tensile test used a speed of 30 mm/min with termination of the test defined at 300 mm of material displacement The gauge length for the samples was set as 300 mm Rheological analyses were conducted on a representative sample for each composite using a DHR-2 controlled stress rotational rheometer (TA Instruments United States) equipped with an environmental test chamber to guarantee the strict control over the temperature during the tests The analysis was done using a 25 mm parallel plate geometry keeping a constant temperature of 220°C to mimic the value used during FFF processing of the filaments The Sr2+ release behaviour of both inorganic phases and the produced composite filaments was investigated with Inductively Coupled Plasma Atomic Emission Spectrometry Technique (ICP-AES) (ICP-MS At each time point the samples were centrifuged at 10,000 rpm for 5 min (Hermle Labortechnik Z326 Half of the supernatant was collected and then replaced by the same amount of fresh buffer solution The release experiments were carried out in triplicate For the composite filaments, 0.3 g of material (n = 3) were immersed in 3 ml of Tris HCl buffer (same buffer as for the inorganic phases). The soaked fragments were stored in a static oven for 7 days. At each time point the medium was fully refreshed, being substituted with new media (Melo et al., 2019) Experimental data are reported as mean ± standard deviation Statistical differences between groups were analysed using one-way ANOVA with Tukey’s pairwise post-hoc test Statistical significance was represented as *p < 0.05 ***p < 0.001 Both inorganic phases were characterised, focusing on their morphology, composition, and presence of Sr2+, in the desired amount. The MBG_SG_10%Sr particles appeared spherical with nanometric dimensions comprising between 200 and 300 nm (Figure 2A). The EDS analysis confirmed the glass composition based on calcium and silicon oxide as well as the presence of incorporated Sr2+, as evidenced in Figure 2B (A) FE-SEM micrographs of MBG_SG_10%Sr nanoparticles; (B) EDS of MBG_SG_10%Sr showing peaks for Ca O and Sr (arrow) and Cr (from coating); (C) N2 adsorption-desorption curves of MBG_SG_10%Sr; (D) DFT pore size distribution Results from adsorption-desorption analysis on MBG_SG_10%Sr displayed a type IV isotherm, with a H2 hysteresis loop, typically associated with mesoporous materials containing both open and partially blocked mesopores (Figure 2C) (Thommes et al., 2015). The DFT method showed that pore size distribution is centred at 2–3 nm, with a maximum size of 6 nm (Figure 2D) The specific surface area and pore volume were calculated to be 190 m2/g and 0.13 cm3/g 222 and 213 peaks) as confirmed be the values registered in the ICDD database (A) FE-SEM micrographs of HA_50%Sr nanoparticles.; (B) EDS of HA_50%Sr marking peaks for Ca and Sr (arrows) with table indicating the atomic percentage estimated for each element; (C) XRD pattern of HA_50%Sr The ion release test from the MBGs, conducted with Tris-HCl medium, displayed a burst release after 3 h, approximately 60% of the incorporated ions. This was followed by a plateau, where the release continued until day 7, and 95% of the Sr2+ ions left the network (Figure 4A). The ion release test from nano-HA revealed that after 1 day, 20% of the incorporated Sr2+ was released from the sample (Figure 4B) The release kinetics from those particles appeared sustained as 45% of the incorporated ions was measured into the soaking medium (A) MBG_SG_10%Sr nanoparticles; (B) HA_50%Sr The results are expressed as mean ± SD The extruded composite filaments were characterised regarding the inorganic phase distribution into the polymer matrix and to assess its influence over the tensile and rheological properties of the extruded material SEM micrographs of produced filaments cross-section The white arrows indicate the inorganic phases embedded into the PLLA matrix Figure 6A displays representative curves from tensile testing. The ultimate tensile strength of the PLLA_MBG_SG_10%Sr composite was slightly increased when compared to the pure PLLA sample. On the contrary, the PLLA_HA_50%Sr composite displayed a reduction in the mechanical performance. The strain was greater for pure PLLA samples when compared with the composite materials, which were more brittle. The Young Modulus (Figure 6B) increased for PLLA_MBG_SG_10%Sr and decreased for PLLA_HA_50%Sr Tensile properties of the extruded filaments (A) Stress-strain curves; (B) Young Modulus PLLA_MBG_SG_10%Sr and PLLA_HA_50%Sr filaments at 220°C The frequency sweep tests confirmed the viscous behaviour and thus the liquid-state of the material at 220°C for all the analysed samples, where G’’ presented higher values compared to the G’ at lower frequencies (Supplementary Table 1) G’ and G’’ for pure PLLA at low frequencies were measured to be higher than the values shown by the composites storage modulus increased and overcame the loss modulus and indicating the solid-like behaviour of the materials The potential printability of the filaments was tested observing the correspondent flow ramps (Figure 7). All the materials proved to be shear-thinning as a decrease of the viscosity values was observed with increasing shear rates (Barnes, 2003) PLLA displayed the highest value of viscosity about 922 Pa s while the PLLA_MBG_SG_10%Sr samples showed the lowest value At the highest shear rates (100 s−1) all materials showed very low values of viscosity (between 8 and 12 Pa s) The ICP analysis conducted on the extracts of the composite filaments are reported in Table 3 which shows the ability to release of Sr2+ after 7 days with a slightly higher concentration detected for PLLA_HA_50%Sr Values of ultimate tensile strength and Young Modulus for PLLA and composite samples Values of viscosity at a shear rate of 1 and 100 s−1 for PLLA and composite samples Sr2+ ion released from the composite filaments after 7 days of soaking the amount of Sr2+ was further incremented to 10% molar aiming to enhance the final released concentration of this ion from the inorganic phases when embedded into the PLLA polymeric matrix The temperatures and parameters previously listed, for the first extrusion process, were already optimized for pure PLLA filaments, to attain a diameter of 1.7–1.75 mm, compatible with most of FFF printers (Gilmer et al., 2018; Nienhaus et al., 2019) As the material was not sufficiently homogenous upon a first extrusion a second extrusion process was introduced for the composites based on the direct mazing of the inorganic particles in a metal mode the immersion polymer granules in a paste containing the inorganic phase the MBGs are characterized not only by an excellent biocompatibility The ion release kinetics were assessed for both inorganic phases and the hybrid composite filaments in order to evaluate the ability of nano-HA and MBGs to deliver the therapeutic ions alone and when embedded in the polymer matrix for MBGs containing Sr2+ at lower amounts (4% mol.) a burst ion release is observed in the first 2 h of soaking commonly reported for substituted MBGs is due to the high surface area and accessible internal pore volume which greatly enhances the surface ion-exchange reactions especially for framework ions exposed at the pore entrances the majority (95%) of Sr2+ content was released from the silica network A small percentage remained within the mesoporous structure probably due to a partial dissolution and reprecipitation of MBGs framework at the mesopore entrance causing the inaccessibility to the soaking medium At variance, the release curve obtained for Sr2+-substituted nano-HA showed a controlled and prolonged ion delivery associated with the material dissolution. The solubility of nano-HA particles is expected to be affected by the inclusion of Sr2+ into the lattice, resulting higher if compared to non-substituted HA, as previously reported for other substituting ions (Zhu et al., 2018) the amount of MBGs loaded (2 wt%) into the extruded filaments was lower compared to the nano-HA which was 5 wt% and this difference could account for a higher exposure of the latter if fully embedded into the PLLA matrix the internal surface area associated to the mesoporous structure of MBGs would be inaccessible thus not available for ion-exchange reactions with the soaking medium Further degradation tests on the extruded composite filaments are required and will be the subject of future studies in order to investigate and compare the release behaviour over a longer period of time The need for improved devices targeting pathologies such as osteoporosis has created an increasing interest for additive manufactured scaffolds which are capable of mimicking bone composition and mechanical properties this work aims to optimize a hybrid formulation for AM of advanced bone scaffolds through the combination of a medical graded polymer able to promote bone regeneration by stimulating osteogenesis both MBGs and nano-HA were substituted with Sr2+ and the obtained particles combined with PLLA the authors aimed to develop and optimize new approach to produce composite filaments using a combination of manual mixing and solvent free twin-screw extrusion Composite filaments were successfully produced showed a satisfactory dispersion of the inorganic phase and a diameter comparable to the commercially available filaments Both inorganic phases alone when in contact with media mimicking the physiological conditions were able to release Sr2+ The composite extruded filaments also proved to release Sr2+ within 7 days although combined with PLLA matrix preserve their ability to deliver ions associated with pro-osteogenic and anti-clastogenic effects The characterisation of the elastic modulus strength and viscosity showed that the composite materials had broadly similar mechanical and fluid properties as the pure PLLA with the MBG-based composite showing higher strength PLLA and composite filaments showed a shear thinning rheological response highlighting their suitability for FFF printing The proposed composite manufacturing protocol could also be applied to other thermoplastics and inorganic phases which further extends the potential of this method to create bespoke structures it opens the possibility to use a myriad of material combinations The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: 10.5281/zenodo.4155423 RN and IC developed the manufacturing method and interpreted the results under the supervision of CV-B GM conducted the overall rheological characterization and related data interpretation CP synthesized and characterized MBG samples AA and PQ developed the formulations and protocols to produce the nano-HA with 50% Sr2+ substitution IC and GM have written the manuscript and all other authors revised the manuscript and contributed to the discussion of the results CV-B and KD have reviewed and edited the manuscript This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No Author AA and PQ were employed by the company FLUIDINOVA The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmats.2020.601645/full#supplementary-material Synergized poly(lactic acid)–hydroxyapatite composites: biocompatibility study CrossRef Full Text | Google Scholar A comprehensive review of biodegradable synthetic polymer-ceramic composites and their manufacture for biomedical applications CrossRef Full Text | Google Scholar In-situ monitoring of polymer flow temperature and pressure in extrusion based additive manufacturing CrossRef Full Text | Google Scholar Development and characterization of a PLGA-HA composite material to fabricate 3D-printed scaffolds for bone tissue engineering CrossRef Full Text | Google Scholar Fabrication of biocompatible composites of poly(lactic acid)/hydroxyapatite envisioning medical applications CrossRef Full Text | Google Scholar 3D printing of hierarchical scaffolds based on mesoporous bioactive glasses (MBGs)-Fundamentals and applications CrossRef Full Text | Google Scholar Oscillatory and steady shear viscosity: the Cox-Merz rule CrossRef Full Text | Google Scholar A review of the rheology of filled viscoelastic systems CrossRef Full Text | Google Scholar Recent trends in the application of widely used natural and synthetic polymer nanocomposites in bone tissue regeneration CrossRef Full Text | Google Scholar Hydroxyapatite reinforced polyethylene - a mechanically compatible implant material for bone replacement CrossRef Full Text | Google Scholar CrossRef Full Text | Google Scholar Hydroxyapatite (HA)coatings for biomaterials Effect of ceramic filler content on the mechanical and thermal behaviour of poly-l-lactic acid and poly-l-lactic-co-glycolic acid composites for medical applications CrossRef Full Text | Google Scholar 3D printing of scaffolds for tissue regeneration applications CrossRef Full Text | Google Scholar 3D printing of ceramic-based scaffolds for bone tissue engineering: an overview CrossRef Full Text | Google Scholar Fracture healing: mechanisms and interventions PubMed Abstract | CrossRef Full Text | Google Scholar biodegradation and biomedical applications of poly(lactic acid)/poly(lactic-co-glycolic acid) micro and nanoparticles Nanoscaled bioactive glass particles and nanofibres CrossRef Full Text | Google Scholar Accelerated in vitro degradation properties of polylactic acid/phosphate glass fibre composites CrossRef Full Text | Google Scholar The incorporation of strontium to improve bone-regeneration ability of mesoporous bioactive glasses PubMed Abstract | CrossRef Full Text | Google Scholar Enhanced cell proliferation and osteogenic differentiation in electrospun PLGA/hydroxyapatite nanofibre scaffolds incorporated with graphene oxide PubMed Abstract | CrossRef Full Text | Google Scholar The effects of strontium-substituted bioactive glasses on osteoblasts and osteoclasts in vitro CrossRef Full Text | Google Scholar Model analysis of feedstock behavior in fused filament fabrication: enabling rapid materials screening CrossRef Full Text | Google Scholar Substituted hydroxyapatite: a recent development CrossRef Full Text | Google Scholar Electrospun core-sheath poly(vinyl alcohol)/silk fibroin nanofibers with Rosuvastatin release functionality for enhancing osteogenesis of human adipose-derived stem cells PubMed Abstract | CrossRef Full Text | Google Scholar Nanocrystalline calcium phosphate ceramics in biomedical engineering CrossRef Full Text | Google Scholar Multiple and promising applications of strontium (Sr)-containing bioactive glasses in bone tissue engineering PubMed Abstract | CrossRef Full Text | Google Scholar Preparation and mechanical properties of polylactic acid composites containing hydroxyapatite fibers PubMed Abstract | CrossRef Full Text | Google Scholar and hydroxyapatite formation in 27-Tris-SBF for sol-gel based CaO-P2O5-SiO2-B2O 3-ZnO bioactive glasses PubMed Abstract | CrossRef Full Text | Google Scholar Strontium substituted hydroxyapatites: synthesis and determination of their structural properties CrossRef Full Text | Google Scholar Strontium-and cobalt-doped multicomponent mesoporous bioactive glasses (MBGS) for potential use in bone tissue engineering applications PubMed Abstract | CrossRef Full Text | Google Scholar Additive manufacturing methods for producing hydroxyapatite and hydroxyapatite-based composite scaffolds: a review CrossRef Full Text | Google Scholar Do Fabrication of poly(lactic acid)/Ti composite scaffolds with enhanced mechanical properties and biocompatibility via fused filament fabrication (FFF)–based 3D printing CrossRef Full Text | Google Scholar Differentiation of osteoblast and osteoclast precursors on pure and silicon-substituted synthesized hydroxyapatites PubMed Abstract | CrossRef Full Text | Google Scholar 3D printed PCL/SrHA scaffold for enhanced bone regeneration CrossRef Full Text | Google Scholar Effects of inorganic fillers on the thermal and mechanical properties of poly(lactic acid) CrossRef Full Text | Google Scholar Additive manufacturing of tissues and organs CrossRef Full Text | Google Scholar Osteoinduction of 3D printed particulate and short-fibre reinforced composites produced using PLLA and apatite-wollastonite CrossRef Full Text | Google Scholar Additive manufacturing of bioceramic and biocomposite devices for bone repair Short phosphate glass fiber - PLLA composite to promote bone mineralization CrossRef Full Text | Google Scholar Synthetic biodegradable polymers as orthopedic devices CrossRef Full Text | Google Scholar Poly (lactic acid)-based biomaterials for orthopaedic regenerative engineering CrossRef Full Text | Google Scholar CrossRef Full Text | Google Scholar Neščáková Multifunctional zinc ion doped sol – gel derived mesoporous bioactive glass nanoparticles for biomedical applications CrossRef Full Text | Google Scholar Investigations on nozzle geometry in fused filament fabrication CrossRef Full Text | Google Scholar Synthesis and characterization of Zn-Doped hydroxyapatite: scaffold application CrossRef Full Text | Google Scholar Major osteoporotic fragility fractures: risk factor updates and societal impact CrossRef Full Text | Google Scholar An aerosol-spray-assisted approach to produce mesoporous bioactive glass microspheres under mild acidic aqueous conditions CrossRef Full Text | Google Scholar Mesoporous bioactive glass-coated 3D printed borosilicate bioactive glass scaffolds for improving repair of bone defects CrossRef Full Text | Google Scholar The effects of strontium on bone mineral: a review on current knowledge and microanalytical approaches CrossRef Full Text | Google Scholar Melt flow behaviour of poly-ε-caprolactone in fused deposition modelling CrossRef Full Text | Google Scholar Hydroxyapatite–polymer biocomposites for bone regeneration: a review of current trends CrossRef Full Text | Google Scholar Review on the application ofsolid freeform fabrication technology to the production of tissue engineeringscaffolds CrossRef Full Text | Google Scholar Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly L-lactide (PLLA) Part II: practical properties of miniscrews and miniplates CrossRef Full Text | Google Scholar with special reference to the evaluation of surface area and pore size distribution (IUPAC Technical Report) CrossRef Full Text | Google Scholar Development of polymer based biocomposites: a review CrossRef Full Text | Google Scholar Advances in 3D printing of thermoplastic polymer composites and nanocomposites CrossRef Full Text | Google Scholar Developing bioactive composite materials for tissue replacement CrossRef Full Text | Google Scholar 3D printing of polymer matrix composites: a review and prospective CrossRef Full Text | Google Scholar Bioactive mesoporous calcium-silicate nanoparticles with excellent mineralization ability drug-delivery and antibacterial properties for filling apex roots of teeth CrossRef Full Text | Google Scholar Mesoporous bioactive glasses: structure characteristics drug/growth factor delivery and bone regeneration application CrossRef Full Text | Google Scholar Modification and cytocompatibility of biocomposited porous PLLA/HA-microspheres scaffolds CrossRef Full Text | Google Scholar Submicron bioactive glass tubes for bone tissue engineering CrossRef Full Text | Google Scholar CrossRef Full Text | Google Scholar Highly ordered mesoporous bioactive glasses with superior in vitro bone-forming bioactivities CrossRef Full Text | Google Scholar Co-doped hydroxyapatites as potential materials for biomedical applications CrossRef Full Text | Google Scholar Biodegradation and biocompatibility of poly L-lactic acid implantable mesh CrossRef Full Text | Google Scholar Biomimetic component coating on 3D scaffolds using high bioactivity of mesoporous bioactive ceramics CrossRef Full Text | Google Scholar Three dimensionally printed mesoporous bioactive glass and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) composite scaffolds for bone regeneration CrossRef Full Text | Google Scholar Nanostructural insights into the dissolution behavior of Sr-doped hydroxyapatite CrossRef Full Text | Google Scholar Vitale-Brovarone C and Fiorilli S (2020) Processing of Sr2+ Containing Poly L-Lactic Acid-Based Hybrid Composites for Additive Manufacturing of Bone Scaffolds Received: 01 September 2020; Accepted: 30 October 2020;Published: 24 November 2020 Copyright © 2020 Melo, Naseem, Corvaglia, Montalbano, Pontremoli, Azevedo, Quadros, Gentile, Ferreira, Dalgarno, Vitale-Brovarone and Fiorilli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited *Correspondence: Chiara Vitale-Brovarone, Y2hpYXJhLnZpdGFsZUBwb2xpdG8uaXQ= During the day of Sunday, October 23, 2022, four symbolic places of Pontremoli Baroque will be open to the public: theOratory of Nostra Donna, Palazzo Dosi - Magnavacca, Palazzo Pavesi - Ruschi Noceti and Villa Dosi Delfini. For more information 331 8866241 - 366 3712808 - segreteria@pontremolibarocca.it. At 3 p.m. and 4:30 p.m., however, there will be two rounds of tours of Villa Dosi Delfini. This guided tour, however, will need compulsory reservation and will require an entrance fee of €10.00. For more information and reservations 331 8866241 - 366 3712808 - info@sigeric.it. For a day of Baroque in Pontremoli, also not to be missed are visits to the Cathedral of Santa Maria Assunta, the church of San Geminiano and the church of San Francesco. by /// November 23 There are racing cars and there are supercars, but the Dallara Stradale is something else with its curvaceous carbon fiber body and those detachable gull-wing doors, not to mention its almighty 2.3-liter Ford EcoBoost engine. There is no doubt that the Dallara Stradale is one of the sexiest cars to hit the asphalt in the twenty-first century, and it’s no surprise that it hails from the Motor Valley he asked me to build up his dream,” tells Dallara CEO Andrea Pontremoli “He said: I build up cars for everybody I don’t have any car with a plate with my name Dallara wanted to create its first road car – a supercharged and supersexy car to drive to his favourite restaurant in Cinque Terre and then around the track in Mugello it had to look better than anything out there After a few seasons of delay due to prolonged projects development began in 2015 as a birthday promise Gian Paolo came to my office and said: I want to tell you that I am 78 years old And if you build up the car and I’m not still alive Pontremoli delivered the signature yellow Dallara Stradale on November 16 And it’s everything Dallara wanted – extraordinarily lightweight with detachable roof and windshield And Dallara would go on to build 600 units When asked about Motor Valley as a nexus of ingenuity Pontremoli says a lot comes from Italy’s enriched and broad educational programming which sets a great foundation while encouraging creativity and evolution in all sectors including automotive “You cannot build a beautiful car if you don’t have enough base And I think that this is what is needed by the world.” Dallara has decided it is time to evolve education just a little more and with that in mind, it launched Dallara Academy in 2018 The English-language university program is future-focused for the automotive and design world “Dallara Academy is awesome to see because it is where we teach the future engineers of the Motor Valley,” says Pontremoli Formula One and Dallara for a full immersion into practical experience as students study and test designs with the help of those automotive giants and their amazing tools like wind tunnels and driving simulators “We [in Emilia Romagna] have an incredible network of know-how,” explains Pontremoli but we have hundreds of different companies that are around here and they are very specialized in niche things Listen to full interview on the Ciao Bella podcast: Erica Firpo is a travel journalist based in Rome. Founder of CiaoBella and host of CiaoBella podcast. More on Erica at EricaFirpo.com by /// November 9 by /// November 16 by /// March 2 an email (in Italian) with selected contents and upcoming events by /// October 23 by /// November 28 by /// July 31 by /// December 4 For information, contact us: inemiliaromagna@aptservizi.com Il gruppo di Milano: da sinistra a destra Michele Bensi Castaing’s work at Santo Sospir includes a dining room with walls and ceiling covered in split bamboo—a room that inspired Jacques Grange in his work for Yves Saint Laurent and Pierre Bergé at their Villa Mabrouka in Tangier, another magical house set, like this one, high above the sea. The Villa Santo Sospir, breathtakingly situated and saturated in charm and magic, might just be my dream house too. There was just time (at least on Hamish-speed) to dart up the hill to the vast strawberry-pink Villa Ephrussi Rothschild. The villa’s chatelaine was something of an eccentric, with a menagerie of exotic animals amongst her various collections—cranes roamed the gardens, and one of the 18th century dog beds in her bedroom was intended for her pet mongoose. The American press breathlessly reported on a wedding party she had held for two of her lap dogs, complete with wedding gown. The gratin of society were summoned although the invitations were issued to their canine companions. When the baroness died in 1934, she bequeathed these memories, along with her house and gardens, to the Institut de France, to be enjoyed by all. Log in for full access to stabroeknews.com Only one active session is allowed per subscriber who notched up three successive feature race wins to take Formula 3 by storm this year also received the Dallara Award at the Formula 3 Prize Giving Ceremony here this week “It was the best season I’ve ever had in my career,” he said on accepting his prize anyone on the grid had a chance of winning so it was very difficult I made a few mistakes at the beginning of the year didn’t keep the car on track as much as I should’ve we were able to do a great job for the rest of the year So thank you to Trident for giving me the package each weekend I just had to go out there and drive as fast as I can finishing P2 in tricky wet-to-dry conditions before his total reversal of fortunes A sizeable crash in the Sprint Race at Spa-Francorchamps was overcome in the feature event as he claimed his first FIA F3 victory in style He followed that up with a determined drive to victory at Zandvoort up against title rival Victor Martins At the final round and with the Championship in the balance Maloney pulled off another highlight drive to win at the final time of asking doing all he could in pursuit of the Drivers’ Championship although he ended up just five points short of that accolade Red Bull Racing announced the F3 championship runner-up as the newest member of the its junior driver programme and one of the team’s F1 reserve drivers Maloney was 2019 British F4 Champion with Carlin before making the switch to Euroformula Open for 2020 the Bajan driver moved to Formula Regional European Championship by Alpine He took one win along with a further seven podiums on the way to fourth in the standings A FREE roundup of top news from Guyana you might otherwise miss Neighbors and friends gathered to remember Richard "Dickie" Phillips Friday night in Hopkinton was killed in a fire at his Meserve Street home earlier in the week Neighbors Ashley Pontremoli and Keyla Vorce organized the vigil Neighbors spoke aboutt he importance of keeping their community together after the death of their friend Quantum computation aims at the development of new computing devices and algorithms that by taking advantage of genuinely quantum resources such as superposition and entanglement can exponentially reduce the complexity of hard computational problems Continuous variable quantum computation is a specific paradigm that exploits peculiar states of light such as entangled photons and squeezed states to gain a quantum advantage with respect of classical computers for the solution of difficult problems and also to provide novel communication and cryptographic protocols Top racing drivers like Lewis Hamilton can race around the track at over 300km per hour like the way the wind flows around it and how it handles around the bend which substantially contributes to the speed of the car “The name of the game today is speed,” said Dr Andrea Pontremoli an Italian company founded in 1972 to design racing cars “It is really changing a lot of our economy and our way of working because every car wants to win so we need to innovate rapidly too,” he added The sports car design company has turned to supercomputing technology to ramp up its innovation capability A supercomputing cluster enables Dallara engineers to optimise a car’s aerodynamic contours which involves deciding its shape and then running simulations and testing in wind tunnels The company is using a NeXtScale cluster running Lenovo nx360 M5 compute nodes which are two-socket systems that run Intel’s Xeon E5-2600 processor and a software-defined storage solution running on Lenovo System x3650 M5 servers The setup also includes a V3700 V2 storage system and RackSwitch G8052 1/10 Ethernet switch The entire packages runs on Red Hat’s Enterprise Linux operating system Lenovo worked closely with Dallara to produce the cluster executive director of Lenovo’s Data Centre Group said it worked to provide the cluster according to Lenovo’s specifications Dr Pontremoli said that the supercomputer allows the company to work on a new design from a concept on paper to car in just nine months This is critical because eight months are spent on the car’s concept including designing collecting data and reiterating the process until an optimised racing car is completed billions of data points are collected and crunched by the supercomputer which can run aerodynamic features like computational fluid dynamic (CFD) models with 300 million cells in just 2.5 hours The supercomputer can also now run several simulations simultaneously so that different teams and departments do not need to wait to run their analyses Everything that we do is based on one key item the only way to be innovative is to have the possibility to make mistakes,” Dr Pontremoli emphasised “We can’t be novel if we do what we only know,” he told a group of journalists last week at Dallara’s headquarters in Varana de Melegari which is about two hours by car from Milan we’ve to accept that we will make mistakes and the only way to make these mistakes without going bankrupt is through technology,” he added the company cannot build so many real cars for testing because that would take too long and cost too much we go directly from simulation to production because we trust the simulation,” said Dr Pontremoli Lenovo entered the HPC market when it acquired IBM’s server group in 2014 It re-focused this enterprise business on data centres storage and networking hardware and services Technologies such as artificial intelligence (AI) Big Data and blockchain are often included in the systems supplying 174 supercomputer centres in the Top500 list of supercomputers its installations include the Leibniz Supercomputing Centre located near Munich Germany which is the ninth largest supercomputer in the world The iconic Barcelona Supercomputing Centre – located in a retrofitted church in the Spanish capital – also has Lenovo equipment as well as several service providers in China Lenovo’s supercomputing business is expanding in part because it is using commodity-based components like Intel’s Xeon chips in its HPC servers This means more affordable pricing for its customers Dallara may be unknown to sports car racing fans Nascars and other races then they would have seen Dallara’s technology in action Porsche and other top marques in the sports car racing circuit Its work focuses on designing and producing cars that are lightweight by using carbon fibre composite materials; aerodynamics through the use of wind tunnels and 3D modelling; and sports car design It defines the behaviour of a new design by leveraging its supercomputing capabilities to drive simulations and analysing data taken from the wind tunnels “We estimate that out of 100 percent performance of a sports car 15 per cent is contributed by the engine; 35 per cent by the weight and 50 per cent by the aerodynamics Dallara works on the aerodynamics and weight which means we are responsible for 85 per cent of the performance,” said Dr Pontremoli Critical to the development process is simulation which supports the aerodynamic development The HPC together with AI software let engineers accelerate the simulation process as well as find new “behavioural” patterns Dr Pontremoli explained: “We have one billion cells that we use to divide a car more cells mean that cells are smaller and we can get more precise.” “Let’s assume that in a Formula 1 car which has one billion cells and we need to do a calculation to try to understand that behaviour of the car given the shape that we’ve designed,” he added but the front wing will also interact with the rear wing and the flow underneath the car there are some parts of the calculation that will be the same as the previous one so we use AI to recognise a common part,” he said we do what has changed and we keep what is the same.” has poured all his 50 years of expertise into his dream car Production started late last year at the rate of one to two cars a week Only 600 will be produced as Dallara does not want to compete with its racing car customers about 300 Dallara-designed cars compete in racing circuits around the world The data collected from these cars and races adds to its knowledge base which it then leverages to design new cars This knowledge base is being used as Dallara expands its business into a consultancy providing services to other industries like industrial packaging systems and light weight material for aerospace industry This site uses Akismet to reduce spam. Learn how your comment data is processed. Started in June 2008 by technology journalists and ex-journalists in Singapore who share a common love for all things geeky and digital the site now includes segments on personal computing PONTREMOLESE Cacchioli, Franzoni, Miceli, (43' st Cucurnia), Scaldarella, Filippi, Vannucci, Di Santo, Grasselli, Mengali, Baudi, Mancini (36' st Mathibedi). Available: Santini, Lisi, Aliboni, Ceciarini, D'Antogiovanni, Vicairi. Coach Verdi LARCIANESE Cirillo, Porciani, Antonelli, Marianelli, Vallesi, Bagni, (6' pt Capetta, 36' st Romani), Lo Russo (30' st Iannello) Salerno, Ba, Sarti, Terisigni (24' st Ndiaye). Disposable Cannizzaro, Tafi, Maaoruf, Seghi, Mori. Coach Cerasa The match had started badly for the Larcianese, due to the injury suffered by the defender Bathrooms, caused by a fortuitous collision with their own goalkeeper. In the 25th minute the Viola came close to taking the lead, but a close-range shot from Ba just misses the post. In the 28th minute the Pontremoli with a diagonal shot from Of Santo: the ball goes just over the crossbar. At 34' there is a great intervention by Cyril, who saves a header from baudi.