Mechanical and Electrical Properties of Cryo-worked Cu

For manufacturing the magnets of fusion machines pure copper of both high mechanical resistance and electrical conductivity is required. Though high purity copper guarantees high electrical conductivity, its mechanical properties may be not suitable for the applications in tokamaks. In this view, a new procedure developed for obtaining high purity copper with excellent mechanical strength is described in this work. Samples of oxygen free copper (OFC) have been worked by pressing in liquid nitrogen (77 K). It has been verified that the mechanical properties of the worked metal are strongly dependent on the strain rate. Very low strain rates permitted to attain values of tensile yield strength (550 MPa) significantly higher than those obtained by traditional cold-working at room temperature (450 MPa). The electrical conductivity of the cryo-worked Cu decreases with the tensile yield strength even though the hardest samples of tensile yield strength of 550 MPa exhibit still acceptable values of conductivity (about 94 % IACS at room temperature).     

45S5 bioactive glass coatings by atmospheric plasma spraying obtained from feedstocks prepared by different routes

45S5 bioactive glass powders with the composition of 45 SiO₂, 6 P₂O₅, 24.5 CaO and 24.5 wt% Na₂O were melted and quenched in water to obtain a frit. The frit was milled using two different routes: dry milling followed by sieving to obtain glass particles and wet milling followed by spray drying to obtain a powder comprising porous agglomerates. All feedstocks showed adequate characteristics that make them suitable to be deposited by atmospheric plasma spraying. The powders and coatings were characterised by field-emission gun environmental scanning electron microscope and X-ray diffraction. The roughness and the contact angle of the coatings were also determined. The bioactivity of the powders and coatings was assessed by immersion in simulated body fluid. It was found that bioactive glass prepared from bioglass frit by dry milling exhibited similar bioactivity as that of a commercial bioactive glass. All coatings produced showed good adhesion to the substrate as well as suitable surface properties to ensure efficient contact with body fluid. Regardless of the characteristics of the feedstocks or plasma spray conditions used, all coatings were exclusively made up of an amorphous phase. On the other hand, micrographs revealed that the characteristics of the feedstock strongly impact on the final coating microstructure. The most homogeneous microstructure was obtained when the feedstock was prepared by fine dry grinding of the frit. For this coating, the formation of a bioactive layer was also proved by Fourier transform infrared spectroscopy and X-ray diffraction.     

MaxPHOS Ligand: PH/NH Tautomerism and Rhodium‐ Catalyzed Asymmetric Hydrogenations

MaxPHOS is an active and robust P‐stereogenic ligand for asymmetric catalysis. The presence of an  NH bridge between the two phosphine moieties allows the NH/PH tautomerism to take place. The neutral ligand, in which the NH form predominates, is an air‐sensitive compound. However, protonation of MaxPHOS leads to the stable PH form of the ligand, in which the overall positive charge is distributed on both P centers. This protonation turns the MaxPHOS⋅HBF₄ salt 3 into an air‐stable compound both in the solid state and in solution. The salt 3 is also a convenient precursor for the preparation of rhodium(I) complexes by direct ligand exchange with the complex [Rh(acac)(cod)]. Finally, the corresponding rhodium(I)‐MaxPHOS complex was tested in the asymmetric hydrogenation of a wide range of substrates. The complex proved to be a highly selective and robust system in these reactions.

     

New Insights into Dose-Dependent Effects of Curcumin on ARPE-19 Cells

Opposing dose-dependent effects of curcumin (Cur) have been documented in Retinal Pigment Epithelium (RPE); therefore, to shed the light on the mechanisms of action is crucial for ophthalmic applications. On this basis we explored new insights about the dose-dependent mechanisms triggered by Cur in human retinal pigment epithelial cells (ARPE-19). Three concentrations (0.01 mM; 0.05 mM; 0.1 mM) of Cur were tested, followed by morphological, molecular, and functional analysis of the cells. Cur 0.01 mM promotes a significant increase in cell proliferation, not affecting cell cycle progression and apoptosis; by contrast, Cur 0.05 mM and 0.1 mM block cellular proliferation and trigger S-phase cell cycle arrest without inducing apoptosis. The observation of neuronal-like morphological changes in Cur 0.05 mM and 0.1 mM were not associated with neuronal differentiation, as observed by the quantification of Neurofilament-200 and by the analysis of voltage-dependent currents by patch clamp. Evaluation of autophagic markers LC3BII and p62 revealed significant modulations, suggesting an important activation of autophagy in ARPE-19 cells treated with Cur 0.05 mM and Cur 0.1 mM; conversely, Cur 0.01 mM did not affect autophagy. Altogether, our findings show new dose-dependent mechanisms of action of Cur that suggest a wide therapeutic application in ocular diseases with different pathogenesis (i.e., proliferative vitreoretinopathy or Age-Related Macular Degeneration).     

Effects of Physiological and Pathological Urea Concentrations on Human Microvascular Endothelial Cells

Urea is the uremic toxin accumulating with the highest concentration in the plasma of chronic kidney disease (CKD) patients, not being completely cleared by dialysis. Urea accumulation is reported to exert direct and indirect side effects on the gastrointestinal tract, kidneys, adipocytes, and cardiovascular system (CVS), although its pathogenicity is still questioned since studies evaluating its side effects lack homogeneity. Here, we investigated the effects of physiological and pathological urea concentrations on a human endothelial cell line from the microcirculation (Human Microvascular Endothelial Cells-1, HMEC-1). Urea (5 g/L) caused a reduction in the proliferation rate after 72 h of exposure and appeared to be a potential endothelial-to-mesenchymal transition (EndMT) stimulus. Moreover, urea induced actin filament rearrangement, a significant increase in matrix metalloproteinases 2 (MMP-2) expression in the medium, and a significant up- or down-regulation of other EndMT biomarkers (keratin, fibrillin-2, and collagen IV), as highlighted by differential proteomic analysis. Among proteins whose expression was found to be significantly dysregulated following exposure of HMEC-1 to urea, dimethylarginine dimethylaminohydrolase (DDAH) and vasorin turned out to be down-regulated. Both proteins have been directly linked to cardiovascular diseases (CVD) by in vitro and in vivo studies. Future experiments will be needed to deepen their role and investigate the signaling pathways in which they are involved to clarify the possible link between CKD and CVD.     

Is Melanoma Progression Affected by Thyroid Diseases?

Clinical and epidemiological evidence indicate a relationship between thyroid diseases and melanoma. In particular, the hypothyroidism condition appears to promote melanoma spread, which suggests a protective role of thyroid hormones against disease progression. In addition, experimental data suggest that, in addition to thyroid hormones, other hormonal players of the hypothalamic–pituitary–thyroid (HPT) axis, namely the thyrotropin releasing hormone and the thyrotropin, are likely to affect melanoma cells behavior. This information warrants further clinical and experimental studies in order to build a precise pattern of action of the HPT hormones on melanoma cells. An improved knowledge of the involved molecular mechanism(s) could lead to a better and possibly personalized clinical management of these patients.     

Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG2T(G3T)3] and Its Derivatives with an Abasic Site Replacing Single Thymidine

In this paper, we report our investigations on five {"type":"entrez-nucleotide","attrs":{"text":"T30175","term_id":"612273"}}T30175 analogues, prepared by replacing sequence thymidines with abasic sites (S) one at a time, in comparison to their natural counterpart in order to evaluate their antiproliferative potential and the involvement of the residues not belonging to the central core of stacked guanosines in biological activity. The collected NMR (Nuclear Magnetic Resonance), CD (Circular Dichroism), and PAGE (Polyacrylamide Gel Electrophoresis) data strongly suggest that all of them adopt G-quadruplex (G4) structures strictly similar to that of the parent aptamer with the ability to fold into a dimeric structure composed of two identical G-quadruplexes, each characterized by parallel strands, three all-anti-G-tetrads and four one-thymidine loops (one bulge and three propeller loops). Furthermore, their antiproliferative (MTT assay) and anti-motility (wound healing assay) properties against lung and colorectal cancer cells were tested. Although all of the oligodeoxynucleotides (ODNs) investigated here exhibited anti-proliferative activity, the unmodified {"type":"entrez-nucleotide","attrs":{"text":"T30175","term_id":"612273"}}T30175 aptamer showed the greatest effect on cell growth, suggesting that both its characteristic folding in dimeric form and its presence in the sequence of all thymidines are crucial elements for antiproliferative activity. This straightforward approach is suitable for understanding the critical requirements of the G-quadruplex structures that affect antiproliferative potential and suggests its application as a starting point to facilitate the reasonable development of G-quadruplexes with improved anticancer properties.     

Thymosin β4 is differentially expressed in the cerebrospinal fluid of Creutzfeldt‐Jakob disease patients: a MALDI‐TOF MS protein profiling study

MALDI‐TOF protein profiling analysis permits the detection of peptides and small proteins in complex protein mixtures with great accuracy. We applied this analysis to cerebrospinal fluid (CSF) from 15 patients affected by Creutzfeldt‐Jakob disease (CJD). We compared the levels of the normalized ion signals of 11 sporadic and 4 genetic CJD forms with those from ten healthy control subjects and eight non‐CJD relapsing‐remitting multiple sclerosis patients. In so doing, we detected 61 differentially expressed ion signals in CJD samples compared to controls. Among the 61 signals, 3 signals had significantly increased levels with high statistical significance (p <0.0001) and were located at 3238.3 m/z, 4963.7 m/z, and 8565.3 m/z. We characterized the 5.0 and 8.6 kDa proteins as thymosin β4 N‐acetylated and free ubiquitin, respectively, while the 3.2‐kDa peptide remained uncharacterized. Although elevated ubiquitin levels have previously been described in CJD, we have demonstrated for the first time the involvement of thymosin β4 in a neurodegenerative disease. To support the validity of thymosin β4 levels obtained by MALDI‐TOF analysis, an independent enzyme immunoassay analysis was performed. Moreover, a validation cohort consisting of CSF from three CJD patients, five healthy subjects, and six non‐CJD relapsing‐remitting multiple sclerosis patients was analyzed in a similar way, yielding superimposable results. We propose that thymosin β4 is a potential new candidate marker for the ante mortem diagnosis of CJD disease.     

Making Workflow Change Acceptable

Virtual professional communities are supported by network information systems composed from standard Internet tools. To satisfy the interests of all community members, a user-driven approach to requirements engineering is proposed that produces not only meaningful but also acceptable specifications. This approach is especially suited for workflow systems that support partially structured, evolving work processes. To ensure the acceptability, social norms must guide the specification process. The RENISYS specification method is introduced, which facilitates this process using composition norms as formal representations of social norms. Conceptual graph theory is used to represent four categories of knowledge definitions: type definitions, state definitions, action norms and composition norms. It is shown how the composition norms guide the legitimate user-driven specification process by analysing a case on the development of an electronic law journal.