“ri-” e “di-”

Introduzione alla Special Section ri- e di-: Prefissi e paradigmi per rifare e disfare gli Stati Uniti dentro e fuori i confini

The intracrystalline microstructure of Monte Fico lizardite, by optics, μ -Raman spectroscopy and TEM

Abstract. The Monte Fico lizardite crystals have an internal skeletal spongy microstructure, formed by two micrometric domains having different optical reliefs. This intracrystalline microstructure parallels the previously reported intercrystalline arrangement, consisting of lizardite prisms within a chrysotile plus polygonal serpentine matrix. In the high-wavenumber region, the larger and more abundant domains (that represent approximately 87 % of the total field view) produce μ-Raman spectra characterized by two major peaks at 3686 and 3705 cm−1. The smaller, less abundant domains present a wide band confined between these wavenumbers. These features are interpreted as lizardite and chrysotile, respectively. Raman results are confirmed by TEM, which emphasizes the presence of well-recognizable polygonal serpentine too. Tight crystallographic control exists between lizardite and this first serpentine generation. A second serpentine generation occurs perpendicularly to the first one. The lizardite crystals grew up with a skeletal habit, whereas chrysotile fibres and polygonal serpentine filled the voids, growing epitactically on the lizardite crystals, with fast crystal growth in a fluid-rich environment

Crossmodal Semantic Congruence Interacts with Object Contextual Consistency in Complex Visual Scenes to Enhance Short-Term Memory Performance

Object sounds can enhance the attentional selection and perceptual processing of semanticallyrelated visual stimuli. However, it is currently unknown whether crossmodal semantic congruence also affects the post-perceptual stages of information processing, such as short-term memory (STM), and whether this effect is modulated by the object consistency with the background visual scene. In two experiments, participants viewed everyday visual scenes for 500 ms while listening to an object sound, which could either be semantically related to the object that served as the STM target at retrieval or not. This defined crossmodal semantically cued vs. uncued targets. The target was either in- or out-of-context with respect to the background visual scene. After a maintenance period of 2000 ms, the target was presented in isolation against a neutral background, in either the same or different spatial position as in the original scene. The participants judged the same vs. different position of the object and then provided a confidence judgment concerning the certainty of their response. The results revealed greater accuracy when judging the spatial position of targets paired with a semantically congruent object sound at encoding. This crossmodal facilitatory effect was modulated by whether the target object was in- or out-of-context with respect to the background scene, with out-of-context targets reducing the facilitatory effect of object sounds. Overall, these findings suggest that the presence of the object sound at encoding facilitated the selection and processing of the semantically related visual stimuli, but this effect depends on the semantic configuration of the visual scene

A SYSTEMATIC STUDY REGARDING THE IMPORTANCE OF OBTAINING ECOLABEL IN ROMANIA

The purpose of this paper is to review and present a short synthesis of the scientific literature on Ecolabel and an analysis of the types of products and services in Romania that obtained this environmental label. European eco-label is the only environmental quality label (type I; ISO 14024), awarded at institutional level (EC) valid all around the Europe, and it represents a unique opportunity to satisfy consumer expectations. In this way is promotes the design, production and marketing of products with lower environmental impact during their entire life cycle compared to other products in the same category. The EU Ecolabel covers a wide range of product groups, from major areas of manufacturing to tourist accommodation services. Key experts, in consultation with main stakeholders, develop the criteria for each product group in order to decrease the main environmental impacts over the entire life cycle of the product. Because the life cycle of every product and service is different, the criteria are tailored to address the unique characteristics of each product type. The European Ecolabel was introduced in Romania in 2002

A SYSTEMATIC STUDY REGARDING THE IMPORTANCE OF OBTAINING ECOLABEL IN ROMANIA

The purpose of this paper is to review and present a short synthesis of the scientific literature on Ecolabel and an analysis of the types of products and services in Romania that obtained this environmental label. European eco-label is the only environmental quality label (type I; ISO 14024), awarded at institutional level (EC) valid all around the Europe, and it represents a unique opportunity to satisfy consumer expectations. In this way is promotes the design, production and marketing of products with lower environmental impact during their entire life cycle compared to other products in the same category. The EU Ecolabel covers a wide range of product groups, from major areas of manufacturing to tourist accommodation services. Key experts, in consultation with main stakeholders, develop the criteria for each product group in order to decrease the main environmental impacts over the entire life cycle of the product. Because the life cycle of every product and service is different, the criteria are tailored to address the unique characteristics of each product type. The European Ecolabel was introduced in Romania in 2002

The Titanium Surface Modulates the Expression of Beta-Catenin and DLX5 Genes in Pancreatic Ductal Carcinoma in Vitro. Can the Metallic Stent Increase PDAC Aggressiveness?

Context Adenoductal pancreas (PDAC) is a fatal cancer. Its aggressiveness is associated in part with the EMT process of metastasis. Two genes specifically involved in these phenomena are b-catenin and DLX5. While the first gene has been widely studied also in pancreatic cancer, few data are associated with DLX5. However, its over-expression has been recently associated with the formation of metastases in breast cancer in vivo. An exogenous factor involved in the modulation of the expression of these genes seems to be titanium. This compound is usually employed for the pallia action of patients with PDAC, to reduce choledochal stenosis due to compression. Objective The purpose of this study was to assess whether titanium is able to modulate the expression of these two genes in vitro. Methods We used a primary cell culture of PADC (PP78). The cells were seeded and cultivated in contact with two different titanium surfaces for 10 days. After this period the total mRNA was extracted and the quantification of β-catenin and DLX5 genes was performed by RT-PCR according to the ΔΔCt analysis. Then cells were stained using the immunofluorescence technique (IF) to quantify the b-catenin protein expression .using a computerized high-resolution acquisition system (D-Sight, Menarini, Florence, Italy) The cells were scored evaluating the cytoplasmic positivity as follows (0 absent, 1 low, 2 middle, 3 strong). The experiment was carried out in triplicate and untreated cells (without titanium contact) were used as control. Results Quantitative analyses showed that both titanium surfaces positively affected beta-catenin (mean 2.8 fold) and DLX5 (2.0 fold) mRNA expressions with respect to the controls (P<0.0007). Both titanium surfaces also increased the protein score 3 values of β-catenin in treated cells with respect to their controls (P=0.0158). Conclusion Our data showed that several titanium surfaces positively modulated the expression of two genes associated with the increase of the aggressiveness of PDAC in vitro. Clinical studies are needed to find out which type of stent can be used in the surgical operation with palliative intent

Unveiling Novel Therapeutic Targets for CAR Therapy in Multiple Myeloma through Single-Cell RNA Sequencing

Multiple Myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells. Among the different therapeutic options in this setting, chimeric antigen receptor (CAR) T cells recently showed unprecedent achievements in term of progression free survival. However, despite advancements in current therapies, the disease's heterogeneity remains a major challenge and all patients unavoidably relapse, rendering innovative approaches to identify precise therapeutic targets eagerly awaited. Along this line, the revolution of single-cell (sc) technologies brings new opportunities to identify precise therapeutic targets, including abundant and unique surface proteins for CAR therapy. In this study, by analyzing individual cancer cells at sc level, we aim to identify novel surface targets, facilitating the development of novel personalized cellular therapies as well as treatment sequences. To this end, we used samples collected from 9 publicly available single-cell RNA sequencing (scRNA-seq) datasets (GEO accession numbers: GSE176131, GSE189460, GSE223060, GSE210079, GSE145977, GSE124310, GSE161801, GSE163278, GSE161722) obtained from 156 patients affected by monoclonal gammopathies (19 monoclonal gammopathy of undetermined significance (MGUS), 10 smoldering multiple myeloma (SMM), 78 MM and 25 relapsed/refractory multiple myeloma (RRMM)) and 24 normal bone marrows (NBM), to conduct an unbiased search for genes showing specific expression in plasma cells (PCs), regardless of disease status. We found 15 genes showing differential expression in PCs (adj.pval<0.01 and logFC>1) and coding for surface proteins: TNFRSF17(BCMA), SDC1 (CD138), FCRL5 (GPRC5D), TNFRSF13B (TACI), CD38, SLAMF7 (CS1), CD59, FCGR2B, FGFR3, SLC44A1 (CTL1), CD320, FCRL2, IL15RA, INSR and SLAMF1. As expected, most of these molecules already represent critical therapeutic targets. After completing our initial analysis, we compared PCs transcriptomes from MM/RRMM patients with NBM, MGUS, and SMM samples. Among previously identified genes, CD320 only was significantly overexpressed in MM PCs. Next, we investigated associations between cytogenetic-related cell subclusters and previously identified surface markers. Interestingly, we found a significant association between the expression levels of TACI/CD59 and the overexpression of CCND2 and MAF, both associated with the presence of t(14:16). Next, we decided to focus on the first five genes (according to expression ranking) that do not currently have an active clinical development program in advanced phases, namely: TNFRSF13B, CD59, FCGR2B, SLC44A1, and CD320 (Fig. 1 A, values dichotomized based on their median) to uncover their (potential) impact/association with patient's outcome. In our analysis of different available expression profiling datasets (GSE4204, GSE2658, GSE57317, GSE4581, GSE4452, GSE9782, the CoMMpass study NCT01454297) involving around 2000 MM patients, we observed TNFRSF13B, CD59, and FCGR2B expression correlated with improved outcome while CD320 and SLC44A1 expression associated with worse outcome (Fig. 1 B). In conclusion, we integrated results from both scRNAseq and bulk-RNAseq/microarray data to identify new targets genes to be used in the context of personalized medicine. Interestingly, CD320 emerges as a potential candidate biomarker useful for monitoring disease evolution and predicting worse outcomes. Additionally, this approach led us to identify a series of potential new targets for MM patients, depicting a new scenario where each patient could be “screened” to identify the best molecule to be targeted. While further investigation is necessary to assess off-target toxicity and confirm clinical relevance, our analyses significantly streamline the search for tumor markers with a method potentially applicable to different malignancies, bringing us closer to identifying the best candidates for effective CAR therapy

Phase II trial of bevacizumab and dose/dense chemotherapy with cisplatin and metronomic daily oral etoposide in advanced non-small-cell-lung cancer patients.

Bevacizumab, is a humanized monoclonal antibody to vasculo-endothelial- growth-factor, with anticancer activity in non-small-cell-lung cancer (NSCLC) patients. Our previous results from a dose/finding phase I trial in NSCLC patients, demonstrated the anti-angiogenic effects and toxicity of a newest bevacizumab-based combination with fractioned cisplatin and daily oral etoposide. We designed a phase II trial to evaluate in advanced NSCLC patients the antitumor activity and the safety of this novel regimen. In particular, 45 patients (36 males and 9 females), with a mean age of 54 years, an ECOG ≤2, stage III B/IV and NSCLC (28 adenocarcinomas, 11 squamous-cell carcinomas, 2 large-cell carcinomas, 4 undifferentiated carcinomas), were enrolled. They received cisplatin (30 mg/sqm, days 1-3), oral etoposide (50 mg, days 1-15) and bevacizumab (5 mg/kg, day 3) every 3 weeks (mPEBev regimen). Patients who achieved an objective response or stable disease received maintenance treatment with bevacizumab in combination with erlotinib until progression. Grade I-II hematological, mucosal toxicity and alopecia were the most common adverse events. The occurrence of infections (17%), thromboembolic events (4.4%) and severe mood depression (6.7%) was also recorded. A partial response was achieved in 31 (68.8%) patients, disease remained stable in 8 (17.8%) and disease progressed in 6 (13.3%) with a progression-free-survival of 9.53 months (95% CI, 7.7-11.46). Our bio-chemotherapy regimen resulted very active in advanced NSCLC, however, the toxicity associated with the treatment requires strict selection of the patients to enroll in future studies. © 2011 Landes Bioscience