Exploring the effect of fluid dynamics and kinetic mechanisms on n-heptane autoignition in transient jets

The influence of physical parameters and of flow patterns on the prediction of n-heptane ignition dynamic in transient reacting n-heptane jets, in high pressure environment under laminar conditions, has been explored by using different kinetic mechanisms. Some preliminary transient laminar flamelet computations have been performed, thus showing that the sensitivity of the ignition time to strain rate depends on the kinetic mechanism used.Therefore, the structure of the reacting jet, in particular the localization of ignition spots, is investigated. The results show that, if the initial temperature of the reacting mixture is out of the intermediate range (800–1000 K) towards lower values, the fluid dynamics has an essential role. In this case, the ignition delay time is almost insensitive to the specific kinetic mechanism adopted, conversely it is severely shortened by increasing the streamwise velocity. The burning spot is located in the core of fuel roll-up, where low values of scalar dissipation rate occur. Nevertheless, the most reactive mixture fraction conditions are well predicted by chemical kinetics, as they are in good agreement with those computed for the one-dimensional diffusion layer. When the initial temperature of fuel and air is increased in the intermediate range, ignition is strongly dependent on the kinetic mechanism used. In these cases, the choice of an accurate chemical scheme is fundamental in order to obtain reliable results.     

Limit cycles in nonlinear excitation of clusters of classical oscillators

In this paper we develop a numerical procedure for detecting the existence of limit cycles in nonlinear excitation of clusters of classical harmonic oscillators. Our technique is able to compute also the main parameters of a limit cycle, that is the amplitudes and the period. The numerical method, based on the propagation matrix formalism, is transparent and easy to apply. It may find application in various areas where nonlinear excitations are involved, e.g., sound and mechanic vibrations in musical instruments, ground vibrations in volcanic areas, and sea tides.     

Neural networks for blind-source separation of Stromboli explosion quakes

Independent component analysis (ICA) is used to analyze the seismic signals produced by explosions of the Stromboli volcano. It has been experimentally proved that it is possible to extract the most significant components from seismometer recorders. In particular, the signal, eventually thought as generated by the source, is corresponding to the higher power spectrum, isolated by our analysis. Furthermore, the amplitude of the source signals has been found by using a simple trick and so overcoming, for this specific case, the classical problem of ICA regarding the amplitude loss of the separated signals.     

Tissue engineering and the development of Apligraf, a human skin equivalent

In recent years, skin grafting has evolved from the initial autograft and allograft preparations to biosynthetic and tissue-engineered living skin replacements. This review details the pioneering work of numerous investigators that led to the following precursors of tissue-engineered skin replacement: cultured autologous keratinocyte grafts, cultured allogeneic keratinocyte grafts, autologous/allogeneic composites, acellular collagen matrices, and cellular matrices. It also discusses the rationale for the development of the newer products and describes the technical advances leading to the development of Apligraf, a tissue-engineered human skin product.     

In vitro evaluation of freeze-dried bone allografts combined with platelet rich plasma and human bone marrow stromal cells for tissue engineering

Freeze-dried bone allograft (FDBA) might be more effective in combination with platelet rich plasma (PRP) and bone marrow stromal cells (BMSC) in accelerating bone healing. The isolation of BMSC through density gradient (pBMSC) is not extensively applicable in clinical practice, because it increases the risk of infection. Alternatively, BMSC can be concentrated by simple centrifugation (wBMSC) directly in the operating room. However, we do not know if wBMSC act in the same way as pBMSC. BMSC from 10 donors were tested whether, in the presence of a combination of FDBA and autologous PRP, the osteogenic differentiation of the cells concentrated by simple centrifugation (wBMSC + FDBA + PRP) was similar to that of pBMSC. Cell-associated alkaline phosphatase, osterix and fibroblast growth factor-2 were higher in wBMSC + FDBA + PRP. In conclusion, the combination of FDBA and PRP had a favouring effect on the differentiation towards osteoblasts and allowed BMSC concentrated by simple centrifugation to differentiate as fast as BMSC purified by density gradient.     

Complex Refractive Indices of Cd<Subscript><Emphasis Type="Italic">x</Emphasis></Subscript>Zn<Subscript>1−<Emphasis Type="Italic">x</Emphasis></Subscript>O Thin Films Grown by Molecular Beam Epitaxy

The complex refractive indices of Cd _x Zn_1−x O thin films were determined by transmission spectrophotometry. Transmission spectra were modeled from 375 nm to 800 nm for samples having cadmium concentrations ranging from 2% to 77%. The transparent and absorptive regimes were fitted separately by Sellmeier and Forouhi–Bloomer models, respectively. Real refractive indices of Cd _x Zn_1−x O shift to higher values in the transparent region and the optical absorption edge shifts to longer wavelengths with increasing cadmium concentration. Spectroscopic ellipsometry was carried out on one sample from λ = 190 nm to 1.8 μm. Comparison between the two methods shows that the results are in general agreement.     

All-trans-retinoic acid counteracts endothelial cell procoagulant activity induced by a human promyelocytic leukemia-derived cell line (NB4)

Therapy with all-trans-retinoic acid (ATRA) can rapidly improve the coagulopathy of acute promyelocytic leukemia (APL). This study was designed to evaluate whether the APL cell line NB4 induces the procoagulant activity (PCA) of human endothelial cells (ECs) in vitro, and whether this property is modified after ATRA-induced NB4 maturation. EC monolayers were incubated for 4 hours at 37 degrees C with the conditioned media (CM) of NB4 treated with 1 mumol/L ATRA (ATRA-NB4-CM) or the vehicle (control-NB4-CM). EC lysates were tested for PCA. ATRA-NB4-CM induced significantly more PCA:tissue factor (TF) than control-NB4-CM (P < .01). To identify the cause of TF induction, interleukin (IL)-1 beta antigen levels were measured in CM samples. ATRA-NB4-CM contained significantly more IL-1 beta than control-NB4-CM. EC PCA was significantly inhibited by an anti-IL-1 beta antibody. The addition to the media of 10 mumol/L ATRA counteracted the EC TF expression induced by NB4-CM. These data indicate that ATRA increases the promyelocyte-induced EC TF, partly through increased IL-1 beta production. However, ATRA can protect the endothelium from the procoagulant stimulus of leukemic cells.     

Functional Characterization of Two Novel Mutations in SCN5A Associated with Brugada Syndrome Identified in Italian Patients

Background. Brugada syndrome (BrS) is an autosomal dominantly inherited cardiac disease characterized by “coved type” ST-segment elevation in the right precordial leads, high susceptibility to ventricular arrhythmia and a family history of sudden cardiac death. The SCN5A gene, encoding for the cardiac voltage-gated sodium channel Nav1.5, accounts for ~20–30% of BrS cases and is considered clinically relevant. Methods. Here, we describe the clinical findings of two Italian families affected by BrS and provide the functional characterization of two novel SCN5A mutations, the missense variant Pro1310Leu and the in-frame insertion Gly1687_Ile1688insGlyArg. Results. Despite being clinically different, both patients have a family history of sudden cardiac death and had history of arrhythmic events. The Pro1310Leu mutation significantly reduced peak sodium current density without affecting channel membrane localization. Changes in the gating properties of expressed Pro1310Leu channel likely account for the loss-of-function phenotype. On the other hand, Gly1687_Ile1688insGlyArg channel, identified in a female patient, yielded a nearly undetectable sodium current. Following mexiletine incubation, the Gly1687_Ile1688insGlyArg channel showed detectable, albeit very small, currents and biophysical properties similar to those of the Nav1.5 wild-type channel. Conclusions. Overall, our results suggest that the degree of loss-of-function shown by the two Nav1.5 mutant channels correlates with the aggressive clinical phenotype of the two probands. This genotype-phenotype correlation is fundamental to set out appropriate therapeutical intervention.     

Design and Characterization of a Peptide Mimotope of the HIV-1 gp120 Bridging Sheet

The Bridging Sheet domain of HIV-1 gp120 is highly conserved among the HIV-1 strains and allows HIV-1 binding to host cells via the HIV-1 coreceptors. Further, the bridging sheet domain is a major target to neutralize HIV-1 infection. We rationally designed four linear peptide epitopes that mimic the three-dimensional structure of bridging sheet by using molecular modeling. Chemically synthesized peptides BS3 and BS4 showed a fair degree of antigenicity when tested in ELISA with IgG purified from HIV(+) broadly neutralizing sera while the production of synthetic peptides BS1 and BS2 failed due to their high degree of hydrophobicity. To overcome this limitation, we linked all four BS peptides to the COOH-terminus of GST protein to test both their antigenicity and immunogenicity. Only the BS1 peptide showed good antigenicity; however, no envelope specific antibodies were elicited upon mice immunization. Therefore we performed further analyses by linking BS1 peptide to the NH2-terminus of the E2 scaffold from the Geobacillus Stearothermophylus PDH complex. The E2-BS1 fusion peptide showed good antigenic results, however only one immunized rabbit elicited good antibody titers towards both the monomeric and oligomeric viral envelope glycoprotein (Env). In addition, moderate neutralizing antibodies response was elicited against two HIV-1 clade B and one clade C primary isolates. These preliminary data validate the peptide mimotope approach as a promising tool to obtain an effective HIV-1 vaccine.     

Shuttle‐Mediated Nanoparticle Delivery to the Blood–Brain Barrier

Many therapeutic drugs are excluded from entering the brain due to their lack of transport through the blood–brain barrier (BBB). The development of new strategies for enhancing drug delivery to the brain is of great importance in diagnostics and therapeutics of central nervous diseases. To overcome this problem, a viral fusion peptide (gH625) derived from the glycoprotein gH of Herpes simplex virus type 1 is developed, which possesses several advantages including high cell translocation potency, absence of toxicity of the peptide itself, and the feasibility as an efficient carrier for delivering therapeutics. Therefore, it is hypothesized that brain delivery of nanoparticles conjugated with gH625 should be efficiently enhanced. The surface of fluorescent aminated polystyrene nanoparticles (NPs) is functionalized with gH625 via a covalent binding procedure, and the NP uptake mechanism and permeation across in vitro BBB models are studied. At early incubation times, the uptake of NPs with gH625 by brain endothelial cells is greater than that of the NPs without the peptide, and their intracellular motion is mainly characterized by a random walk behavior. Most importantly, gH625 peptide decreases NP intracellular accumulation as large aggregates and enhances the NP BBB crossing. In summary, these results establish that surface functionalization with gH625 may change NP fate by providing a good strategy for the design of promising carriers to deliver drugs across the BBB for the treatment of brain diseases.