Nanoparticles-cell association predicted by protein corona fingerprints

In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a "protein corona" layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø ≈ 100-250 nm) and surface chemistry (unmodified and PEGylated) to investigate the relationships between NP physicochemical properties (nanoparticle size, aggregation state and surface charge), protein corona fingerprints (PCFs), and NP-cell association. We found out that none of the NPs' physicochemical properties alone was exclusively able to account for association with human cervical cancer cell line (HeLa). For the entire library of NPs, a total of 436 distinct serum proteins were detected. We developed a predictive-validation modeling that provides a means of assessing the relative significance of the identified corona proteins. Interestingly, a minor fraction of the HC, which consists of only 8 PCFs were identified as main promoters of NP association with HeLa cells. Remarkably, identified PCFs have several receptors with high level of expression on the plasma membrane of HeLa cells

Nanoparticles-cell association predicted by protein corona fingerprints

In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a "protein corona" layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø ≈ 100-250 nm) and surface chemistry (unmodified and PEGylated) to investigate the relationships between NP physicochemical properties (nanoparticle size, aggregation state and surface charge), protein corona fingerprints (PCFs), and NP-cell association. We found out that none of the NPs' physicochemical properties alone was exclusively able to account for association with human cervical cancer cell line (HeLa). For the entire library of NPs, a total of 436 distinct serum proteins were detected. We developed a predictive-validation modeling that provides a means of assessing the relative significance of the identified corona proteins. Interestingly, a minor fraction of the HC, which consists of only 8 PCFs were identified as main promoters of NP association with HeLa cells. Remarkably, identified PCFs have several receptors with high level of expression on the plasma membrane of HeLa cells

Firms’ Proactiveness During the Crisis: Evidence from European Data

none3This paper contributes to the literature on the entrepreneurial behavior of firms during the economic crisis by investigating the determinants of proactive behavior on a large sample of European companies during the 2008–2009 financial crisis. We explore various dimensions of proactive behavior, including: investments in innovation, expanding product offer, undergoing quality certification, investing in tangible assets and avoiding layoff. Our findings show a surprising heterogeneity of determinants in the case of different proactivity measures, especially when considering the impact of public policies which support entrepreneurship. We also provide some evidence supporting the organizational learning hypothesis with regard to proactiveness, as we show that the previous crisis experience matters in the case of the adoption of proactive or reactive strategy by a firm.openJan Brzozowski; Marco Cucculelli; Valentina PeruzziBrzozowski, Jan Pawel; Cucculelli, Marco; Peruzzi, Valentin

Family firms and regional entrepreneurship. The European evidence

none3noopenRICCARDO CAPPELLI, MARCO CUCCULELLI, VALENTINA PERUZZICappelli, Riccardo; Cucculelli, Marco; Peruzzi, Valentin

Finite element analysis applied to redesign of submerged entry nozzles for steelmaking

The production of steel by continuous casting is facilitated by the use of refractory hollow-ware components. A critical component in this process is the submerged entry nozzle (SEN). The normal operating conditions of the SEN are arduous, involving large temperature gradients and exposure to mechanical forces arising from the flow of molten steel; experimental development of the components is challenging in so hazardous an environment. The effects of the thermal stress conditions in relation to a well-tried design were therefore simulated using a finite element analysis approach. It was concluded from analyses that failures of the type being experienced are caused by the large temperature gradient within the nozzle. The analyses pointed towards a supported shoulder area of the nozzle being most vulnerable to failure and practical in-service experience confirmed this. As a direct consequence of the investigation, design modifications, incorporating changes to both the internal geometry and to the nature of the intermediate support material, were implemented, thereby substantially reducing the stresses within the Al2O3/graphite ceramic liner. Industrial trials of this modified design established that the component reliability would be significantly improved and the design has now been implemented in series production

Nuclear functions of the tyrosine kinase Src

Src is the representative member of the Src-family kinases (SFKs), a group of tyrosine kinases involved in several cellular processes. Its main function has been for long confined to the plasma membrane/cytoplasm compartment, being a myristoylated protein anchored to the cell membrane and functioning downstream to receptors, most of them lacking intrinsic kinase activity. In the last decades, new roles for some SFKs have been described in the nuclear compartment, suggesting that these proteins can also be involved in directly regulating gene transcription or nucleoskeleton architecture. In this review, we focused on those nuclear functions specifically attributable to Src, by considering its function as both tyrosine kinase and adapting molecule. In particular, we addressed the Src involvement in physiological as well as in pathological conditions, especially in tumors

Proof-of-principle of a new geometry for sampling calorimetry using inorganic scintillator plates

A novel geometry for a sampling calorimeter employing inorganic scintillators as an active medium is presented. To overcome the mechanical challenges of construction, an innovative light collection geometry has been pioneered, that minimises the complexity of construction. First test results are presented, demonstrating a successful signal extraction. The geometry consists of a sampling calorimeter with passive absorber layers interleaved with layers of an active medium made of inorganic scintillating crystals. Wavelength-shifting (WLS) fibres run along the four long, chamfered edges of the stack, transporting the light to photodetectors at the rear. To maximise the amount of scintillation light reaching the WLS fibres, the scintillator chamfers are depolished. It is shown herein that this concept is working for cerium fluoride (CeF$_3$) as a scintillator. Coupled to it, several different types of materials have been tested as WLS medium. In particular, materials that might be sufficiently resistant to the High-Luminosity Large Hadron Collider radiation environment, such as cerium-doped Lutetium-Yttrium Orthosilicate (LYSO) and cerium-doped quartz, are compared to conventional plastic WLS fibres. Finally, an outlook is presented on the possible optimisation of the different components, and the construction and commissioning of a full calorimeter cell prototype is presented.Comment: Submitted to Proceedings CALOR 2014, the 16th International Conference on Calorimetry in High-Energy Physics, Giessen (Germany) 6 - 11 April 2014. To be published in Journal of Physics: Conference Series (10 pages, 15 figures

Aortic regurgitation in athletes. Pieces of the puzzle we have so far omitted

The prevalence of valvular heart disease (VHD) rises with age, reaching 11.7% in individuals older than 75 years.1 In young individuals, VHD is usually related to the presence of a congenital valve abnormality, as bicuspid aortic valve (BAV) or mitral valve prolapse. This is also the case for athletes, where in the presence of these abnormalities few restrictions exist in eligibility for competitive sports participation, even if a strict follow-up would be desirable. BAV is the most common congenital valve abnormality (1%) found in the general population and in athletes. BAV is more prevalent in males and it can lead to aortic regurgitation (AR), aortic stenosis and/or aortic root dilation. At present, no definitive studies have proved that intensive sports participation could worsen the progression of BAV and limited data are available on athletes

The influence of non-living mulch, mechanical and thermal treatments on weed population and yield of rainfed fresh-market tomato (Solanum lycopersicum L.)

Weed control is often a major limitation for vegetable crops, since compared to arable crops fewer herbicides are available and the crops are more sensitive to weeds. Field experiments were carried out in the province of Pisa (Central Italy) to determine the effect of two different mulches (black biodegradable plastic film and wheat straw) and mechanical and thermal treatments on weed population and yield of rain-fed fresh market tomato (Solanum lycopersicum L.). Rolling harrow, flaming machine and precision hoe for weed control, which were either built, enhanced or modified by the University of Pisa were used separately (mechanical-thermal strategy) or in combination with a straw mulch (mechanical-thermal-straw strategy). These two innovative strategies were compared with the traditional farming system, which uses a biodegradable plastic mulch film. The strategies were compared in terms of machine performance, weed density, total labour requirement, weed dry biomass, and crop fresh yield at harvest. The total operative time for weed control was on average ~25 h ha-1 for the two systems, which included mulching, and over 30 h ha-1 for the mechanical-thermal strategy. The three strategies controlled weeds effectively, with only 30 g m-2 in each treatment. Tomato yield, however, was 35% higher for strategies that included mulching (both biodegradable film and straw)

Hot foam and hot water for weed control: a comparison

Thermal weed control plays an important role in managing weeds in synthetic herbicide-free systems, particularly in organic agriculture and in urban areas where synthetic herbicides are prohibited. This study compares the impact on weed control of increased doses of hot water and hot foam (i.e. 0, 0.67, 1.67, 3.33, 5.00, 6.67 and 8.33 kg m–2). The doses were applied using the same machine. The temperatures, weed control effectiveness, weed regrowth after the death of the aboveground vegetative weed tissues, and weed dry biomass 30 days after the treatments were studied in two experimental fields with a different weed composition (i.e. Site I and Site II). The results showed that difficult weeds to control, such as Cynodon dactylon (L.) Pers., Digitaria sanguinalis (L.) Scop. and Taraxacum officinale Weber, like all the other species in the initial weed populations in the two experiments, died after lower doses of hot foam compared to hot water. Adding foam to hot water made it possible to lower the required dose of water by at least 2.5-fold compared to hot water used alone. By insulating the weeds, the foam led to higher peak temperatures and slower temperature decay, thus determining an effective weed control with lower doses compared to hot water. Starting from 11 days and 16 days after treatments (for Site I and Site II, respectively), there were no statistically significant differences in weed regrowth between hot foam and hot water at all the doses applied. There were no differences between the dry biomass of weeds collected 30 days after treatments when the same doses of hot foam and hot water were used