Warm Up! An Experimental Project on Design for Social Innovation and Urban Regeneration.

The research aims to share the results from the “Warm Up” Workshop—an experimental project held by PhD Product Design students from Sapienza University of Rome in collaboration with St. Petersburg University (SPbU)— involving students from SPbU’s Graphic Design Master Degree Program. The objective is to apply the topics of Design for Social Innovation and Design for Public Space to investigate the opportunities for new sociability in the social context of Vasilyevsky Island in St. Petersburg. The experimental aspect of the workshop is due to the fusion of methods and approaches typical of Product Design, such as human-centered design (HCD), and the Avant-Garde heritage of the Russian School. By illustrating their concepts of products/services, the students have developed a new practice within the fields of Product Design and User Experience. The final result is to serve a hypothetical urban regeneration in terms of Social Innovation, designing the user experiences as storyboards with the classical structure of “before and after” that would narrate the final change in users’ behaviors

The simultaneous insertion of two ligands in gD for the cultivation of oncolytic HSVs in non-cancer cells and the retargeting to cancer receptors

Insertion of a single chain antibody (scFv) to HER2 (human epidermal growth factor receptor 2) in gD, gH, or gB gives rise to herpes simplex viruses (HSVs) specifically retargeted to HER2-positive cancer cells, hence in highly specific non-attenuated oncolytic agents. Clinical grade virus production can not rely on cancer cells. Recently, we developed a double retargeting strategy whereby gH carries the GCN4 peptide for retargeting to the non-cancer producer Vero-GCN4R cell line, and gD carries the scFv to HER2 for cancer retargeting. Here, we engineered double retargeted recombinants, which carry both the GCN4 peptide and the scFv to HER2 in gD. Novel, more advantageous detargeting strategies were devised, so as to optimize the cultivation of the double-retargeted recombinants. Nectin1 detargeting was achieved by deletion of aa 35-39, 214-223, or 219-223, and replacement of the deleted sequences with one of the two ligands. The latter two deletions were not attempted before. All recombinants exhibited the double retargeting to HER2 and to the Vero-GCN4R cells, as well as detargeting from the natural receptors HVEM and nectin1. Of note, some recombinants grew to higher yields than others. The best performing recombinants carried a gD deletion as small as 5 amino acids, and grew to titers similar to those exhibited by the singly retargeted R-LM113, and by the non-retargeted R-LM5. This study shows that double retargeting through insertion of two ligands in gD is feasible and, when combined with appropriate detargeting modifications, can result in recombinants highly effectivein vitroandin vivo.IMPORTANCEThere is increasing interest in oncolytic viruses, following FDA and EMA approval of the oncolytic HSV OncovexGM-CSF, and, mainly, because they greatly boost the immune response to the tumor and can be combined with immunotherapeutic agents, particularly immune checkpoint inhibitors. A strategy to gain high cancer specificity and avoid virus attenuation is to retarget the virus tropism to cancer-specific receptors of choice. However, cultivation of retargeted oncolytics in cells expressing the cancer receptor may not be approvable by regulatory agencies. We devised a strategy for their cultivation in non-cancer cells. Here, we describe a double retargeting strategy, based on the simultaneous insertion of two ligands in gD, one for retargeting to a producer, universal Vero cell derivative, one for retargeting to the HER2 cancer receptor. These insertions were combined with novel, minimally-disadvantageous detargeting modifications. The current and accompanying studies teach how to best achieve the clinical-grade cultivation of retargeted oncolytics

A Cationic [60] Fullerene Derivative Reduces Invasion and Migration of HT-29 CRC Cells in Vitro at Dose Free of Significant Effects on Cell Survival

Nanomaterials with unique characteristics exhibit favorable therapeutic and diagnostic properties, implying their enormous potential as biomedical candidates. C60 has been used in gene- and drug-delivery, as imaging agents, and as photosensitizers in cancer therapy. In this study, the influences of a cationic functionalized fullerene on cellular behavior of human colorectal cancer cell line (HT-29) were investigated. Results indicated that HT-29 treated with the studied compound showed a lower sensitivity but a significant impairment in migration and invasion by interfering with the activities of matrix metalloproteinases (MMP-2 and 9). The presence of fullerene also altered the capacity of adhesion-related proteins to perform their activity, thereby inducing dramatically adverse effects on the cell physiological functions such as cell adhesion. Thus, our study suggests that this compound is a new potential anti-metastatic effector and a therapeutic component for malignant colorectal cancer

Bright, point X-ray source based on a commercial portable 40 ps Nd:YAG laser system

We present some experimental results on X-ray spectra obtained from plasmas produced using a compact Nd:YAG laser system. The beam was focused on different targets (Cu, Al, Ge,…) and both high resolution and low resolution X-ray spectra were recorded

polyphenols from vitis vinifera lambrusco by products leaves from pruning extraction parameters evaluation through design of experiment

Vitis vinifera L. leaves from pruning are by-products of the wine industry and represent an important source of secondary raw material, thanks to their polyphenols content. Optimization of the extraction processes is a key factor for their valorization, and Design of Experiment (DOE) could be a tool to obtain the most performing extract in terms of polyphenols quality/quantity and bioactivity. Vitis vinifera Lambrusco leaves were subjected to ultrasound-assisted extractions guided by a 23 factorial design. Three independent parameters (% solvent, time of extraction, and solvent:solid ratio) were considered to evaluate the extraction process by analyzing the extraction yield, the total phenolic content (Folin-Ciocalteu assay), and the antioxidant capacity (DPPH assay). Moreover, the content of the main molecules was identified and quantified by reversed-phase high-performance liquid chromatography coupled with diode array detection and mass spectrometry. The DOE highlighted the best extraction conditions that showed slight changes considering the different evaluating parameters. The highest extraction yield was obtained by extraction with 100% water, 60 minutes of extraction time, and 30:1 solvent:solid ratio, but it was neither the richest in polyphenols nor antioxidant capacity. The latter 2 characteristics were associated with the extraction performed using 50% ethanol, 35 minutes of extraction time, and a 20:1 solvent:solid ratio. That extract also exhibited the highest quantity of flavonols

Efficacy of Systemically Administered Retargeted Oncolytic Herpes Simplex Viruses—Clearance and Biodistribution in Naïve and HSV-Preimmune Mice

We investigated the anticancer efficacy, blood clearance, and tissue biodistribution of systemically administered retargeted oncolytic herpes simplex viruses (ReHVs) in HSV-naive and HSV-preimmunized (HSV-IMM) mice. Efficacy was tested against lung tumors formed upon intravenous administration of cancer cells, a model of metastatic disease, and against subcutaneous distant tumors. In naive mice, HER2- and hPSMA-retargeted viruses, both armed with mIL-12, were highly effective, even when administered to mice with well-developed tumors. Efficacy was higher for combination regimens with immune checkpoint inhibitors. A significant amount of infectious virus persisted in the blood for at least 1 h. Viral genomes, or fragments thereof, persisted in the blood and tissues for days. Remarkably, the only sites of viral replication were the lungs of tumor-positive mice and the subcutaneous tumors. No replication was detected in other tissues, strengthening the evidence of the high cancer specificity of ReHVs, a property that renders ReHVs suitable for systemic administration. In HSV-IMM mice, ReHVs administered at late times failed to exert anticancer efficacy, and the circulating virus was rapidly inactivated. Serum stability and in vivo whole blood stability assays highlighted neutralizing antibodies as the main factor in virus inactivation. Efforts to deplete mice of the neutralizing antibodies are ongoing

Variable Stars and Stellar Populations in Andromeda XXVII. IV. An Off-centered, Disrupted Galaxy

We present B and V time-series photometry of the M31 satellite galaxy Andromeda XXVII (And XXVII) that we observed with the Large Binocular Cameras of the Large Binocular Telescope. In the field of And XXVII we have discovered a total of 90 variables: 89 RR Lyrae stars and 1 Anomalous Cepheid. The average period of the fundamental mode RR Lyrae stars (RRab) < {P}{ab}> =0.59 {days} (σ = 0.05 day) and the period–amplitude diagram place And XXVII in the class of Oosterhoff I/Intermediate objects. Combining information from the color–magnitude diagram (CMD) and the variable stars, we find evidence for a single old and metal-poor stellar population with [Fe/H] ∼ ‑1.8 dex and t ∼ 13 Gyr in And XXVII. The spatial distributions of RR Lyrae and red giant branch (RGB) stars give clear indication that And XXVII is a completely disrupted system. This is also supported by the spread observed along the line of sight in the distance to the RR Lyrae stars. The highest concentration of RGB and RR Lyrae stars is found in a circular area of 4 arcmin in radius, centered about 0.°2 in the southeast direction from Richardson et al.’s center coordinates of And XXVII. The CMD of this region is well-defined, with a prominent RGB and 15 RR Lyrae stars (out of the 18 found in the region) tracing a very tight horizontal branch at < V({RR})> =25.24 {mag} σ = 0.06 mag (average over 15 stars). We show that And XXVII is a strong candidate building block of the M31 halo. Based on data collected with the Large Binocular Cameras at the Large Binocular Telescope, PI: G. Clementini

Dystonias: rehabilitation

Articles in the MedLine (PubMed) database and other research sources were reviewed, with no time limit. The search strategy used was based on structured questions in the PICO format from the initials: Patient, Intervention, Control and Outcome. The descriptors used were: dystonia and (benzodiazepines or baclofen or tizanidine or clodinine): dystonia and (anticholinergics or haloperidol or lisuride); dystonia and (botulinum toxin); dystonia cervical and (speech therapy or speech pathologist or botulinum toxin); focal dystonia and (botulinum toxin); dystonia and (sensory stimulation or sensory rehabilitation); dystonia and (biofeedback or electromyography biofeedback); dystonia and (transcranial magnetic stimulation); (dystonic disorders or dystonia) and (self help devices or assistive technology or assistive technologies or rehabilitation); dystonia and (activity daily living); dystonias and (neurosurgery not intrathecal baclofen).Foram revisados artigos nas bases de dados do MedLine (PubMed) e outras fontes de pesquisa, sem limite de tempo. A estratégia de busca utilizada baseou-se em perguntas estruturadas na forma P.I.C.O. (das iniciais "Paciente", "Intervençao", "Controle", "Outcome"). Foram utilizados como descritores: dystonia and (benzodiazepines or baclofen or tizanidine or clodinine): dystonia and (anticholinergics or haloperidol or lisuride); dystonia and (botulinum toxin); dystonia cervical and (speech therapy or speech pathologist or botulinum toxin); focal dystonia and (botulinum toxin); dystonia and (sensory stimulation or sensory rehabilitation); dystonia and (biofeedback or electromyography biofeedback); dystonia and (transcranial magnetic stimulation); (dystonic disorders or dystonia) and (self help devices or assistive technology or assistive technologies or rehabilitation); dystonia and (activity daily living); dystonias and (neurosurgery not intrathecal baclofen)

Genomewide association study for onset age in Parkinson disease

<p>Abstract</p> <p>Background</p> <p>Age at onset in Parkinson disease (PD) is a highly heritable quantitative trait for which a significant genetic influence is supported by multiple segregation analyses. Because genes associated with onset age may represent invaluable therapeutic targets to delay the disease, we sought to identify such genetic modifiers using a genomewide association study in familial PD. There have been previous genomewide association studies (GWAS) to identify genes influencing PD susceptibility, but this is the first to identify genes contributing to the variation in onset age.</p> <p>Methods</p> <p>Initial analyses were performed using genotypes generated with the Illumina HumanCNV370Duo array in a sample of 857 unrelated, familial PD cases. Subsequently, a meta-analysis of imputed SNPs was performed combining the familial PD data with that from a previous GWAS of 440 idiopathic PD cases. The SNPs from the meta-analysis with the lowest p-values and consistency in the direction of effect for onset age were then genotyped in a replication sample of 747 idiopathic PD cases from the Parkinson Institute Biobank of Milan, Italy.</p> <p>Results</p> <p>Meta-analysis across the three studies detected consistent association (p < 1 × 10^-5) with five SNPs, none of which reached genomewide significance. On chromosome 11, the SNP with the lowest p-value (rs10767971; p = 5.4 × 10^-7) lies between the genes <it>QSER1 </it>and <it>PRRG4</it>. Near the PARK3 linkage region on chromosome 2p13, association was observed with a SNP (rs7577851; p = 8.7 × 10^-6) which lies in an intron of the <it>AAK1 </it>gene. This gene is closely related to <it>GAK</it>, identified as a possible PD susceptibility gene in the GWAS of the familial PD cases.</p> <p>Conclusion</p> <p>Taken together, these results suggest an influence of genes involved in endocytosis and lysosomal sorting in PD pathogenesis.</p

The origins and spread of domestic horses from the Western Eurasian steppes

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: All collapsed and paired-end sequence data for samples sequenced in this study are available in compressed fastq format through the European Nucleotide Archive under accession number PRJEB44430, together with rescaled and trimmed bam sequence alignments against both the nuclear and mitochondrial horse reference genomes. Previously published ancient data used in this study are available under accession numbers PRJEB7537, PRJEB10098, PRJEB10854, PRJEB22390 and PRJEB31613, and detailed in Supplementary Table 1. The genomes of ten modern horses, publicly available, were also accessed as indicated in their corresponding original publications57,61,85-87.NOTE: see the published version available via the DOI in this record for the full list of authorsDomestication of horses fundamentally transformed long-range mobility and warfare. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling at Botai, Central Asia around 3500 BC. Other longstanding candidate regions for horse domestication, such as Iberia and Anatolia, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 BC, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 BC driving the spread of Indo-European languages. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium BC Sintashta culture