F. De Angelis

The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation

We describe a pathway by which the master transcription factor PU.1 regulates human monocyte/macrophage differentiation. This includes miR-424 and the transcriptional factor NFI-A. We show that PU.1 and these two components are interlinked in a finely tuned temporal and regulatory circuitry: PU.1 activates the transcription of miR-424, and this up-regulation is involved in stimulating monocyte differentiation through miR-424-dependent translational repression of NFI-A. In turn, the decrease in NFI-A levels is important for the activation of differentiation-specific genes such as M-CSFr. In line with these data, both RNAi against NFI-A and ectopic expression of miR-424 in precursor cells enhance monocytic differentiation, whereas the ectopic expression of NFI-A has an opposite effect. The interplay among these three components was demonstrated in myeloid cell lines as well as in human CD34+ differentiation. These data point to the important role of miR-424 and NFI-A in controlling the monocyte/macrophage differentiation program.

6-Alkyl- and 5,6-Dialkyl-2-methoxy-4(3H)-pyrimidinones in the Transformations of Pyrimidines. Conversion into 2-Substituted Amino- and 4-Chloro-Pyrimidine-Derivatives

Abstract 6-Alkyl- and 5,6-dialkyl-2-methoxy-4(3H)-pyrimidinones are transformed into the 2-alkyl(and 2-aryl)amino-derivatives, in good yield, by reaction with the corresponding amines. Treatment with SOCl2 -DMF gives 6-alkyl- and 5,6-dialkyl-2-methoxy-4-chloro pyrimidines.

6-alkyl and 5,6-dialkyl-2-methoxy-4(3H)- pyrimidinones in the transformations of pyrimidines—2: Synthesis and conversion into alkyluracils and 2-alkoxy-4(3H)-pyrimidinones

Abstract The synthesis of 6-alkyl and 5,6-dialkyl-2-methoxy- 4 ( 3H )-pyrimidinones 3 is described. Their versatility to be transformed into 6-alkyl and 5,6-dialkyluracils 4 ( a-h ), 6-alkyl and 5,6-dialkyl-3-methyluracils 7 ( a , e , f ) and 6-alkyl and 5,6-dialkyl-2-alkoxy-4(3H)-pyrimidinones 5 ( a-i ) is also shown.

Mood and coping in clinically isolated syndrome and multiple sclerosis

Few studies have examined behavioural changes in the early phase of multiple sclerosis (MS). The aim of the study is to investigate mood alterations and to explore coping strategies regarding patients with clinically isolated syndrome (CIS) and relapsing‐remitting MS (RRMS).

Bleeding phenotype and correlation with factor XI (FXI) activity in congenital FXI deficiency: Results of a retrospective study from a single centre

Bleeding phenotype in factor XI (FXI)‐deficient patients is variable, and not related to baseline FXI:Act. Aims of our study were to describe the characteristics and the management of surgery and deliveries in FXI‐deficient patients, and to investigate the relationship between the haemorrhagic phenotype and the baseline FXI:Act. Ninety‐five patients were diagnosed and followed in our centre for a median follow‐up of 0.9 years (0.1–36.2); median FXI:Act of all patients: 38% (0.5–69%). Fifty‐six patients (59%) experienced bleeding episodes not surgery‐related. Prior to diagnosis, 64 patients underwent 132 surgeries, and after diagnosis, 23 patients underwent 36 surgeries. Globally 26 of 168 surgeries were prophylactically treated, whereas 142 of 168 were not. As regard as surgeries performed without prophylaxis, 30 bleeding events (21%) occurred in 21 patients. At diagnosis, the median FXI:Act of bleeding and non‐bleeding patients was 28% and 37%, respectively, without statistically significant difference between the two groups (P = 0.26). As regard as surgeries performed under prophylactic treatment just 1 bleeding event occurred. Prior to diagnosis, 31 spontaneous deliveries (SD) and eight caesarian sections (CS) were performed without prophylaxis: 4 postpartum haemorrhages (10.5%) occurred (patients FXI:Act: 2%, 6%, 27%, 52.3% respectively). After diagnosis, four SD and five CS were performed with prophylaxis: no postpartum haemorrhages occurred. We confirm the wide bleeding phenotype variability in FXI‐deficient patients, not related to the baseline FXI:Act levels. We highlight the importance of performing a correct diagnosis and follow‐up, because a good management of prophylactic treatment, dramatically reduces the bleeding rate in case of surgery or deliveries.

Experimental issues in magnetic force microscopy of nanoparticles

The development of magnetic nanoparticles for biomedical applications requires a detailed characterization of their magnetic properties, with relation not only to their chemical structure, but also their morphology and size. Magnetic force microscopy (MFM), thanks to its nanometric lateral resolution and its capability to detect weak magnetic fields, appears as a powerful tool for the characterization of the magnetic properties of single nanoparticles, together with their morphological characteristics. Nevertheless, the application of MFM to the quantitative measurements of magnetic properties at the nanoscale is still an open issue because of a certain incongruence between experimental data and existing theoretical models of the tip-sample magnetic interactions. In this work, MFM data acquired on different magnetic nanoparticles in different experimental conditions (magnetized and not magnetized probes, out-of-field and in-field measurements) are analyzed, with the aim of individuating the possible phenomena affecting MFM measurements. These include topography-induced artifacts resulting from the tip-sample capacitive coupling, which we propose here for the first time. In case of measurements performed in presence of an external magnetic field, much more intense MFM signals were detected as it produces the saturation of the magnetization of the nanoparticles, which is not completely obtained by the sole stray field produced by the tip. Nevertheless, even in in-field measurements, the results evidenced the presence of significant electrostatic effects in MFM images, which, therefore, appear as an important factor to be taken into account for the quantitative interpretation of MFM data.

Dehydration of tertiary bicyclo[3.3.1]nonan-9-ol-2-ones. Rearrangement to cis-fused hexahydroinden-1-ones

Abstract Dehydrations of the anti -ketol 5 and its isomer 10 have been studied. In both cases the 1-hydrindenones 6 and 7 have been almost quantitatively obtained (1:1 ratio) through skeletal rearrangement of the kinetically favoured 9-methylene bicyclononane 9 . This strongly supports the hypothesis of a stepwise rearrangement driven by the relative stabilities of the involved carbonium ions.

Antimicrobial activity of graphene nanoplatelets against Streptococcus mutans

In recent years, several studies have demonstrated the strong cytotoxicity toward bacteria of graphene-based materials, suggesting their use as antimicrobial agents. The objective of this study was to evaluate the antibacterial activity against Streptococcus mutans, the principal microbiological agent in the etiology of dental caries, of two types of graphene nanoplatelets (GNPs), characterized by different thickness and lateral dimensions of the flakes. The antimicrobial properties of GNPs were valued on some plaque and saliva samples extracted from children with dental caries. Our results show that the killing effect of GNPs on S. mutans cells is both lateral size and thickness dependent. In fact, lower thickness and smaller size GNPs exhibit stronger antibacterial activity than larger and thicker ones. Scanning electron microscopy analysis revealed that GNPs interact strongly with cells. This study suggests that GNPs may be highly effective against S. mutans and therefore caries.

Relationship between Prolactin Plasma Levels and White Matter Volume in Women with Multiple Sclerosis

Background. The role of prolactin (PRL) on tissue injury and repair mechanisms in multiple sclerosis (MS) remains unclear. The aim of this work was to investigate the relationship between PRL plasma levels and brain damage as measured by magnetic resonance imaging (MRI). Methods. We employed a chemiluminescence immunoassay for measuring plasma levels of PRL. We used a 1.5 T scanner to acquire images and Jim 4.0 and SIENAX software to analyse them. Results. We included 106 women with relapsing remitting (RR) MS and stable disease in the last two months. There was no difference in PRL plasma levels between patients with and without gadolinium enhancement on MRI. PRL plasma levels correlated with white matter volume (WMV) (rho = 0.284, p = 0.014) but not with grey matter volume (GMV). Moreover, PRL levels predicted changes in WMV (Beta: 984, p = 0.034). Conclusions. Our data of a positive association between PRL serum levels and WMV support the role of PRL in promoting myelin repair as documented in animal models of demyelination. The lack of an increase of PRL in the presence of gadolinium enhancement, contrasts with the view considering this hormone as an immune-stimulating and detrimental factor in the inflammatory process associated with MS.

A Data Center performance comparison analysis between Tier III architecture and a CCHP alternative solutions

Nowadays, the servers capabilities are on the increase at or beyond the rate of performance predicted by Moores Law. The IT services, with the advent of cloud computing, become an increasingly critical part of everyday business activities, and then the power consumption of todays data centers skyrockets due to the rapid growth of their scales and the high required reliability levels. These aspects aggravate, significantly, the operational cost of data centers. The Uptime Institutes Tier Classification System affords a reliable method to compare typically unique, customized facilities based on expected site infrastructure performance. During the last decades many Data Centers architecture solutions have been investigated in order to reducing the overall costs. The Combined Cooling, Heating, and Power (CCHP) systems have the potential to decrease carbon emission and air pollution and to increase resource energy efficiency significantly. To mitigate the negative loop between the IT service growth and power consumption and to evaluate the data center power infrastructure energy impact, on equivalent availability requirements contests, the aim of this paper is to propose a set of equivalent reference schemes for developing and comparing PUE evaluation. The construction of this set is made by comparing a standard TIERIII topology, in agreement to Uptime Institute gradient definition with CCHP solutions.