Immersive Appian Way health infrastructure: human centric Digital Twin (The PAAA Archeological Park of the Appian Way 12km State-Own Section, Unesco Candidature)

From Rome to Benevento, the Appian Way (Via Appia Antica) was born as a military road, 'Regina Viarum'. In 312 b.C., consul Appio Claudio extended the infrastructure for 132 miles to Capua. Many transformations and integration occurred across the centuries, resulting in a unique multi-stratified world heritage (landscape, architecture, archaeological remains and tombs along the military way). In the 19th century, Luigi Canina conceived the Appian Way as an outdoor museum, realizing a first state-own section along the 12km here surveyed and described. This year, the Ministry of Culture (MIC) has launched the UNESCO nomination for the road. The article discusses aspects of the mass digitization undertaken by the Parco Archeologico dell'Appia Antica (PAAA, the Archaeological Park of the Appian Way). The aim is to build a Digital Twin of the infrastructure supporting knowledge enhancement, preservation, design, communication and fruition. A virtual space where digital technologies and eXtended Reality are the digital arms of the contemporary Vitruvian humanistic mission and vision of the PAAA Appian Way as a source of wealth and healthiness for all the users and visitors

From “Learning by Doing” to Closing the Cycle with a Demonstration Effect: the Story about Nuclear Fuel Reprocessing in Argentina

Entre los emprendimientos que lanzó en la década del 60 la Comisión Nacional de Energía Atómica (CNEA), organismo argentino responsable de la investigación, el desarrollo y el asesoramiento en materia nuclear, se destaca el reprocesamiento de combustibles nucleares gastados. Dicha tecnología separa, con distintos fines, uranio, plutonio y residuos radiactivos del combustible irradiado. Este artículo aborda los proyectos de reprocesamiento que se encadenaron en CNEA entre 1962 y 1976: las Plantas de Reprocesamiento 1 y 2 y el Ensamble de Reprocesamiento Experimental. El foco está puesto en las decisiones técnicas y políticas que orientaron cada proyecto, sus continuidades y discontinuidades, así como los contextos que los habilitaron. La hipótesis que guía la argumentación es que los proyectos se corresponden con distintos paradigmas de política científica y tecnológica. Más precisamente, se corresponden con diferentes lógicas de definición de objetivos y de prácticas de trabajo, de justificación de sus contenidos, de estrategias de toma de decisión y de expectativas en torno a las posibilidades y los efectos del desarrollo local de ciencia y tecnología.Entre os empreendimentos lançados na década de 60 pela Comissão Nacional de Energia Atómica (CNEA) - organismo argentino responsável pela pesquisa, desenvolvimento e consultoria nuclear, destaca-se o reprocessamento de combustíveis nucleares gastos. Essa tecnologia separa, com diversos fins, urânio, plutônio e resíduos radiativos do combustível irradiado. Este artigo aborda os projetos de reprocessamento que se encadearam na CNEA entre 1962 e 1976: as Instalações de Reprocessamento 1 e 2, e a Montagem de Reprocessamento Experimental. O foco está nas decisões técnicas e nas políticas que orientaram cada projeto, suas continuidades e descontinuidades, bem como os contextos em que foram habilitados. A hipótese que orienta a argumentação é que os projetos se correspondem com diferentes paradigmas de política científica e tecnológica. Mais precisamente, eles se correspondem com diferentes lógicas de definição de objetivos e de práticas de trabalho, de justificação de seus conteúdos, de estratégias de tomada de decisão e de expectativas em torno às possibilidades e os efeitos do desenvolvimento local de ciência e tecnologia.Among the initiatives introduced in the 1960s by the National Atomic Energy Commission (CNEA, due to its initials in Spanish), the Argentine agency responsible for nuclear research, development and consultancy, the reprocessing of spent nuclear fuels stands out. This technology separates uranium, plutonium and radioactive waste from irradiated fuel for different uses. This paper addresses the CNEA fuel reprocessing projects that were launched between 1962 and 1976: Reprocessing Plants 1 and 2 and the Experimental Reprocessing Assembly. The focus is placed on the technical and political decisions that guided each project, their continuities and discontinuities, as well as the environments that enabled them. The hypothesis that guides the arguments made is that these projects correspond to different scientific-technological policy paradigms. More precisely, they correspond to different logics used to define objectives and work practices, rationales to justify their content, decision-making strategies and expectations regarding the possibilities and effects of the local development of this science and technology.Fil: Quilici, Domingo. Comisión Nacional de Energía Atómica; ArgentinaFil: Spivak L'Hoste, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Sociales. Instituto de Desarrollo Económico y Social. Centro de Investigaciones Sociales; Argentin

A minimal cytomegalovirus intron A variant can improve transgene expression in different mammalian cell lines.

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Sustained Activation of Lyn Tyrosine Kinase In Vivo Leads to Autoimmunity

Genetic ablation of the Lyn tyrosine kinase has revealed unique inhibitory roles in B lymphocyte signaling. We now report the consequences of sustained activation of Lyn in vivo using a targeted gain-of-function mutation (Lynup/up mice). Lynup/up mice have reduced numbers of conventional B lymphocytes, down-regulated surface immunoglobulin M and costimulatory molecules, and elevated numbers of B1a B cells. Lynup/up B cells are characterized by the constitutive phosphorylation of negative regulators of B cell antigen receptor (BCR) signaling including CD22, SHP-1, and SHIP-1, and display attributes of lymphocytes rendered tolerant by constitutive engagement of the antigen receptor. However, exaggerated positive signaling is also apparent as evidenced by the constitutive phosphorylation of Syk and phospholipase Cγ2 in resting Lynup/up B cells. Similarly, Lynup/up B cells show a heightened calcium flux in response to BCR stimulation. Surprisingly, Lynup/up mice develop circulating autoreactive antibodies and lethal autoimmune glomerulonephritis, suggesting that enhanced positive signaling eventually overrides constitutive negative signaling. These studies highlight the difficulty in maintaining tolerance in the face of chronic stimulation and emphasize the pivotal role of Lyn in B cell signaling

The megalithic building of S.Erasmo di Cesi: architecture, astronomy, and landscape

Abstract. One of the most enigmatic megalithic buildings of Italy is the structure which lies on the S. Erasmo hill near Cesi, in Umbria, a huge complex encompassing an area of around 8000 square meters and enclosed by refined cyclopean walls. Although its date is uncertain, suggested dates comprise the Iron Age and archaic period, down to the third century B.C. The building’s function is also uncertain. Usually identified as a fortified structure, in fact there is a megalithic platform at the southern end of the enclosure which could have served as foundation of a temple or palace and, from the top of Monte Torre Maggiore, a complex of temples dating from the fourth century B.C. overlooks the hill. Similar combinations of megalithic buildings resting half-way to temples placed on high peaks are known to exist. In order to clarify the function of this structure and its position in relation to the surrounding landscape, with particular attention to its visibility and to the directions of visibility from the complex, as well as to the possible astronomical alignments, we present a multi-disciplinary approach to the study of the S. Erasmo complex, which includes the mapping of the sky at the various possible epochs of construction, the creation of a digital model of the landscape in forms of digital maps using Geographic Information System technologies, and a 3D model using various 3D software packages

Transcriptomic and metabolite analyses of Cabernet Sauvignon grape berry development

BACKGROUND: Grape berry development is a dynamic process that involves a complex series of molecular genetic and biochemical changes divided into three major phases. During initial berry growth (Phase I), berry size increases along a sigmoidal growth curve due to cell division and subsequent cell expansion, and organic acids (mainly malate and tartrate), tannins, and hydroxycinnamates accumulate to peak levels. The second major phase (Phase II) is defined as a lag phase in which cell expansion ceases and sugars begin to accumulate. Véraison (the onset of ripening) marks the beginning of the third major phase (Phase III) in which berries undergo a second period of sigmoidal growth due to additional mesocarp cell expansion, accumulation of anthocyanin pigments for berry color, accumulation of volatile compounds for aroma, softening, peak accumulation of sugars (mainly glucose and fructose), and a decline in organic acid accumulation. In order to understand the transcriptional network responsible for controlling berry development, mRNA expression profiling was conducted on berries of V. vinifera Cabernet Sauvignon using the Affymetrix GeneChip® Vitis oligonucleotide microarray ver. 1.0 spanning seven stages of berry development from small pea size berries (E-L stages 31 to 33 as defined by the modified E-L system), through véraison (E-L stages 34 and 35), to mature berries (E-L stages 36 and 38). Selected metabolites were profiled in parallel with mRNA expression profiling to understand the effect of transcriptional regulatory processes on specific metabolite production that ultimately influence the organoleptic properties of wine. RESULTS: Over the course of berry development whole fruit tissues were found to express an average of 74.5% of probes represented on the Vitis microarray, which has 14,470 Unigenes. Approximately 60% of the expressed transcripts were differentially expressed between at least two out of the seven stages of berry development (28% of transcripts, 4,151 Unigenes, had pronounced (≥2 fold) differences in mRNA expression) illustrating the dynamic nature of the developmental process. The subset of 4,151 Unigenes was split into twenty well-correlated expression profiles. Expression profile patterns included those with declining or increasing mRNA expression over the course of berry development as well as transient peak or trough patterns across various developmental stages as defined by the modified E-L system. These detailed surveys revealed the expression patterns for genes that play key functional roles in phytohormone biosynthesis and response, calcium sequestration, transport and signaling, cell wall metabolism mediating expansion, ripening, and softening, flavonoid metabolism and transport, organic and amino acid metabolism, hexose sugar and triose phosphate metabolism and transport, starch metabolism, photosynthesis, circadian cycles and pathogen resistance. In particular, mRNA expression patterns of transcription factors, abscisic acid (ABA) biosynthesis, and calcium signaling genes identified candidate factors likely to participate in the progression of key developmental events such as véraison and potential candidate genes associated with such processes as auxin partitioning within berry cells, aroma compound production, and pathway regulation and sequestration of flavonoid compounds. Finally, analysis of sugar metabolism gene expression patterns indicated the existence of an alternative pathway for glucose and triose phosphate production that is invoked from véraison to mature berries. CONCLUSION: These results reveal the first high-resolution picture of the transcriptome dynamics that occur during seven stages of grape berry development. This work also establishes an extensive catalog of gene expression patterns for future investigations aimed at the dissection of the transcriptional regulatory hierarchies that govern berry development in a widely grown cultivar of wine grape. More importantly, this analysis identified a set of previously unknown genes potentially involved in critical steps associated with fruit development that can now be subjected to functional testing.National Science Foundation Plant Genome Project (DBI-0217653); Bioinformatics program (DBI-0136561); National Institute of Health Biomedical Research Infrastructure Network (NIH-NCRR P20 RR16464; National Institute of Health IDeA Network of Biomedical Research Excellence (INBRE, RR-03-008); Nevada Agricultural Experimental Statio

Treatment of Cavernous Sinus Aneurysms with Flow Diversion: Results in 44 Patients

ABSTRACT BACKGROUND AND PURPOSE: Aneurysms of the cavernous segment of the ICA are difficult to treat with standard endovascular techniques, and ICA sacrifice achieves a high rate of occlusion but carries an elevated level of surgical complications and risk of de novo aneurysm formation. We report rates of occlusion and treatment-related data in 44 patients with cavernous sinus aneurysms treated with flow diversion

Multi-drug resistant Vibrio cholerae O1 variant El Tor isolated in northern Vietnam between 2007 and 2010

Since 2007, there has been a re-emergence of cholera outbreaks in northern Vietnam. To understand the molecular epidemiological relatedness and determine the antibiotic susceptibility profiles of responsible V. cholerae O1 outbreak strains, a representative collection of 100 V. cholerae O1 strains was characterized. V. cholerae O1 strains isolated from diarrhoeal patients in northern Vietnam between 2007 and 2010 were investigated for antibiotic susceptibility and characterized by using phenotypic and genotypic tests, including PFGE analysis. Ten clinical V. cholerae O1 isolates from Bangladesh and Zimbabwe were included for comparison. The results revealed that all isolates were resistant to co-trimoxazole and nalidixic acid, 29 % were resistant to tetracycline and 1 % were resistant to azithromycin. All strains were susceptible to ampicillin–sulbactam, doxycycline, chloramphenicol and ciprofloxacin and 95 % were susceptible to azithromycin. MIC values did show reduced susceptibility to fluoroquinolones and 63 % of the strains were intermediately resistant to tetracycline. The isolates expressed phenotypic traits of both serogroup O1 Ogawa and El Tor and harboured an rstR El Tor and ctxB classical biotype. Among the outbreak isolates, only a single PFGE pattern was observed throughout the study period. This study shows that multi-drug resistant V. cholerae altered El Tor producing classical CT strains are now predominant in northern Vietnam

A tetracationic porphyrin with dual anti-prion activity

Prions are deadly infectious agents made of PrPSc, a misfolded variant of the cellular prion protein (PrPC) which self-propagates by inducing misfolding of native PrPC. PrPSc can adopt different pathogenic conformations (prion strains), which can be resistant to potential drugs, or acquire drug resistance, hampering the development of effective therapies. We identified Zn(II)-BnPyP, a tetracationic porphyrin that binds to distinct domains of native PrPC, eliciting a dual anti-prion effect. Zn(II)-BnPyP binding to a C-terminal pocket destabilizes the native PrPC fold, hindering conversion to PrPSc; Zn(II)-BnPyP binding to the flexible N-terminal tail disrupts N- to C-terminal interactions, triggering PrPC endocytosis and lysosomal degradation, thus reducing the substrate for PrPSc generation. Zn(II)-BnPyP inhibits propagation of different prion strains in vitro, in neuronal cells and organotypic brain cultures. These results identify a PrPC-targeting compound with an unprecedented dual mechanism of action which might be exploited to achieve anti-prion effects without engendering drug resistance

Eff ectiveness of one dose of oral cholera vaccine in response to an outbreak: a case-cohort study

Background Oral cholera vaccines represent a new eff ective tool to fi ght cholera and are licensed as two-dose regimens with 2–4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the fi rst fi eld deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine eff ectiveness study in conjunction with this large public health intervention. Methods We did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the fi rst day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confi rmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India). Findings Between Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classifi ed as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine eff ectiveness was 80·2% (95% CI 61·5–100·0) and after adjusting for potential confounders was 87·3% (70·2–100·0). Interpretation One dose of Shanchol was eff ective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological settings