Percutaneous Coronary Intervention (PCI) Reprograms Circulating Extracellular Vesicles from ACS Patients Impairing Their Cardio-Protective Properties

Extracellular vesicles (EVs) are promising therapeutic tools in the treatment of cardiovascular disorders. We have recently shown that EVs from patients with Acute Coronary Syndrome (ACS) undergoing sham pre-conditioning, before percutaneous coronary intervention (PCI) were cardio-protective, while EVs from patients experiencing remote ischemic pre-conditioning (RIPC) failed to induce protection against ischemia/reperfusion Injury (IRI). No data on EVs from ACS patients recovered after PCI are currently available. Therefore, we herein investigated the cardio-protective properties of EVs, collected after PCI from the same patients. EVs recovered from 30 patients randomly assigned (1:1) to RIPC (EV-RIPC) or sham procedures (EV-naive) ({"type":"clinical-trial","attrs":{"text":"NCT02195726","term_id":"NCT02195726"}}NCT02195726) were characterized by TEM, FACS and Western blot analysis and evaluated for their mRNA content. The impact of EVs on hypoxia/reoxygenation damage and IRI, as well as the cardio-protective signaling pathways, were investigated in vitro (HMEC-1 + H9c2 co-culture) and ex vivo (isolated rat heart). Both EV-naive and EV-RIPC failed to drive cardio-protection both in vitro and ex vivo. Consistently, EV treatment failed to activate the canonical cardio-protective pathways. Specifically, PCI reduced the EV-naive Dusp6 mRNA content, found to be crucial for their cardio-protective action, and upregulated some stress- and cell-cycle-related genes in EV-RIPC. We provide the first evidence that in ACS patients, PCI reprograms the EV cargo, impairing EV-naive cardio-protective properties without improving EV-RIPC functional capability.     

Quantitation of lysinoalanine in dairy products by liquid chromatography–mass spectrometry with selective ion monitoring

The unnatural amino acid lysinoalanine (LAL) has been identified in milk and cheese products by liquid chromatography mass spectrometry (LC/ESI/MS) with selective ion monitoring (SIM) of the 9-fluorenyl-methylchloro-formate (FMOC) derivative. LAL is not present in raw milk or derived from Mozzarella cheese; however, high amounts of LAL are found in calcium caseinate and milk powder. As expected, milk fortified with caseinate or whey protein powder produces cheese with higher LAL content. Our analytical procedure is based on the simultaneous detection of specific ion masses of the FMOC–LAL derivative and the N-ε-methyl-lysine internal standard. A linear relationship was observed within the 0.2–20 ppm concentration range, in addition to a high correlation coefficient and ∼3% relative standard deviation.     

Mechanical fatigue analysis of gold microbeams for RF-MEMS applications by pull-in voltage monitoring

This work is focused on the reliability of gold microcantilevers under the effect of mechanical fatigue. A dedicated device for testing the material is designed and built; the material degradation is monitored during the tests by means of a novel technique based on the control of the pull-in voltage of the device, which was demonstrated to be related to the loss of mechanical strength. The fatigue effect is produced through the excitation of the device at a frequency near the resonance; the excitation frequency and the time of actuation are used as a counter for the number of cycles. The lifetime of the device is measured under variable levels of vibration amplitudes; the number of cycles to failure is estimated within a specific range of actuation voltages by means of the W?hler diagram obtained by experiments. The fatigue limit is also estimated following the stair-case method.     

ECHO: a digital library for historical film archives

Easy access to large information collections is of great importance in many aspects of everyday life. However, limitations in information and communication technologies have so far prevented the average person from taking much advantage of existing resources. Historical documentaries held by national archives constitute some of the most precious yet least accessible cultural information. The ECHO project has facilitated accessibility to this type of precious information by developing a digital library (DL) service for historical films belonging to large national audiovisual archives.     

Impact of negative feedback in metabolic noise propagation

Synthetic biology combines different branches of biology and engineering aimed at designing synthetic biological circuits able to replicate emergent properties useful for the biotechnology industry, human health and environment. The role of negative feedback in noise propagation for a basic enzymatic reaction scheme is investigated. Two feedback control schemes on enzyme expression are considered: one from the final product of the pathway activity, the other from the enzyme accumulation. Both schemes are designed to provide the same steady‐state average values of the involved players, in order to evaluate the feedback performances according to the same working mode. Computations are carried out numerically and analytically, the latter allowing to infer information on which model parameter setting leads to a more efficient noise attenuation, according to the chosen scheme. In addition to highlighting the role of the feedback in providing a substantial noise reduction, our investigation concludes that the effect of feedback is enhanced by increasing the promoter sensitivity for both schemes. A further interesting biological insight is that an increase in the promoter sensitivity provides more benefits to the feedback from the product with respect to the feedback from the enzyme, in terms of enlarging the parameter design space.Inspec keywords: biotechnology, enzymes, biological techniquesOther keywords: negative feedback impact, metabolic noise propagation, mathematical modelling, synthetic biological circuit, biotechnology industry, human health, environment, enzymatic reaction scheme, feedback control scheme, enzyme expression, enzyme accumulation, negative autoregulation, steady‐state average value, feedback performance, stochastic simulation algorithm, stochastic hybrid system modelling, noise attenuation, substantial noise reduction, feedback effect, parameter design space     

Dissimilar Resistance Spot Welding of Q&P and TWIP Steel Sheets

Dissimilar resistance spot welding of twinning induced plasticity (TWIP) and quenching and partitioning (Q&P) steel grades has been investigated by evaluating the effects of clamping force, welding current, and welding time on the microstructure, shear tension strength, and fracture of welded samples. The spot welding of TWIP and Q&P steels promotes the occurrence of an asymmetrical weld nugget with a greater dilution of TWIP steel because of its lower melting temperature and thermal conductivity. As a result, weld nuggets exhibit an austenitic microstructure. TWIP steel undergoes a grain coarsening in the HAZ, whereas Q&P steel undergoes some phase transformations. Welded samples tend to exhibit higher shear tension strength as they are joined at the highest welding current, even though an improper clamping force can promote excessive metal expulsion, thereby reducing the mechanical strength of the welded joints. Shear tension welded samples failed through interfacial fracture with partial thickness fracture mode for a low welding current, while partial thickness with button pull fractures were observed when a high welding current was used. The weld spots predominantly failed at the TWIP side. However, as TWIP steel can work harden significantly in the more resistant welded joints, the failures occur, instead, at the Q&P side.     

DILIGENT: integrating digital library and Grid technologies for a new Earth observation research infrastructure

This paper introduces DILIGENT, a digital library infrastructure built by integrating digital library and Grid technologies and resources. This infrastructure allows different communities to dynamically build specialised digital libraries capable to support the entire e-Science knowledge production and consumption life-cycle by using shared computing, storage, content, and application resources. The paper presents some of the main software services that implement the DILIGENT system. Moreover, it exemplifies the provided features by presenting how the DILIGENT infrastructure is being exploited in supporting the activity of user communities working in the Earth Science Environmental sector. This work is partially funded by the European Commission in the context of the DILIGENT project, under the 2nd call of FP6 IST priority.     

A linearized model for estimating the performance of submerged resonant wave energy converters

A realistic performance analysis of oscillating water column wave energy converters (WECs) addresses to a set of non-linear differential equations that need to be integrated in time, by using a stochastic approach, under the hypothesis of random wind-generated sea waves, for all the sea states which characterize the location of the system. Non-linearities of the differential equations have several origins:

• minor and major losses of the unsteady flow of water and air;

• compressibility of air and heat exchange with the walls of the air chamber;

• non-linear characteristics of the turbine.

Under the hypothesis of random sea waves with Gaussian distribution, the authors propose an original methodology for linearizing the differential equations that describe the flow motion inside a wholly submerged WEC. Under such hypothesis, the linearized model can be used for predicting the power output by means of the calculations in the frequency domain and for control design. The developed methodology has been applied to the estimation of the performance of the new “resonant sea wave energy converters”, called REWEC, patented by Boccotti in 1998, and consisting of several caissons, characterized by a structure similar to the caissons of the traditional breakwaters and placed on the seabed, close one to each other, to form a submerged breakwater. Each caisson is connected to a vertical duct wholly beneath the sea level, where a hydraulic Wells turbine is placed.The matching between turbine and resonance characteristic of the system is carefully analysed in order to maximize the energy conversion efficiency.Some results, given for a small installation in the Mediterranean sea, confirm that the REWEC system is able to absorb a large share of the incident wave energy due to a very simple regulation system which permits the tuning on sea states with different significant heights.     

Random amplified polymorphic DNA and amplified ribosomal DNA spacer polymorphism: powerful methods to differentiate Streptococcus thermophilus strains

66 inpatients who met the DSM-III-R and ICD-10 criteria for paranoid schizophrenia-active phase were assessed using the SAPS and CDS in order to establish interrelations between depressive and positive symptomatology. The results were then analyzed in reference do particular items of the scale CDS and the three stages of examinations. Numerous positive correlations were found between depressive symptoms and the symptoms from the subscale of Delusions and Hallucinations SAPS (Delusions of Sin or Guilt, of Mind Reading, of Being Controlled, of Reference, Somatic Delusions and Hallucinations) and negative correlations with the symptoms from the subscale of Positive Formal Thought Disorder.