Statistical and stability analyses of neural pulse frequency modulator Semiannual status report, period ending 1 Feb. 1969

Statistical analysis of neural pulse frequency modulato

Extension and application of a sequential estimator

Improved sequential estimation technique for nonlinear time varying system

Synthesis and matrix properties of α-cyano-5-phenyl-2,4-pentadienic acid (CPPA) for intact proteins analysis by matrix-assisted laser desorption/ionization mass spectrometry

The effectiveness of a synthesized matrix, α-cyano-5-phenyl-2,4-pentadienic acid (CPPA), for protein analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in complex samples such as foodstuff and bacterial extracts, is demonstrated. Ultraviolet (UV) absorption along with laser desorption/ionization mass spectrometry (LDI-MS) experiments were systematically conducted in positive ion mode under standard Nd:YLF laser excitation with the aim of characterizing the matrix in terms of wavelength absorption and proton affinity. Besides, the results for standard proteins revealed that CPPA significantly enhanced the protein signals, reduced the spot-to-spot variability and increased the spot homogeneity. The CPPA matrix was successful employed to investigate intact microorganisms, milk and seed extracts for protein profiling. Compared to conventional matrices such as sinapinic acid (SA), α-cyano-4-hydroxycinnamic acid (CHCA) and 4-chloro-α-cyanocinnamic acid (CClCA), CPPA exhibited better signal-to-noise (S/N) ratios and a uniform response for most examined proteins occurring in milk, hazelnut and in intact bacterial cells of E. coli. These findings not only provide a reactive proton transfer MALDI matrix with excellent reproducibility and sensitivity, but also contribute to extending the battery of useful matrices for intact protein analysis

Evidence for immunomodulation and apoptotic processes induced by cationic polystyrene nanoparticles in the hemocytes of the marine bivalve Mytilus

none8sìPolymeric nanoparticles can reach the marine environment from different sources as weathering of plastic debris and nanowaste. Nevertheless, few data are available on their fate and impact on marine biota. Polystyrene nanoparticles (PS NPs) can be considered as a model for studying the effects of nanoplastics in marine organisms: recent data on amino-modified PS NPs (PS-NH2) toxicity in sea urchin embryos underlined that marine invertebrates can be biological targets of nanoplastics. Cationic PS NPs have been shown to be toxic to mammalian cells, where they can induce apoptotic processes; however, no information is available on their effects and mechanisms of action in the cells of marine organisms. In this work, the effects of 50 nm PS-NH2 were investigated in the hemocytes of the marine bivalve Mytilus galloprovincialis. Hemocytes were exposed to different concentrations (1, 5, 50 μg/ml) of PS-NH2 suspension in ASW. Clear signs of cytoxicity were evident only at the highest concentrations (50 μg/ml). On the other hand, a dose dependent decrease in phagocytic activity and increase in lysozyme activity were observed. PS-NH2 NPs also stimulated increase in extracellular ROS (reactive oxygen species) and NO (nitric oxide) production, with maximal effects at lower concentrations. Moreover, at the highest concentration tested, PS-NH2 NPs induced apoptotic process, as evaluated by Flow cytometry (Annexin V binding and mitochondrial parameters). The results demonstrate that in marine invertebrates the immune function can represent a significant target for PS-NPs. Moreover, in Mytilus hemocytes, PS-NH2 NPs can act through mechanisms similar to those observed in mammalian cells. Further research is necessary on specific mechanisms of toxicity and cellular uptake of nanoplastics in order to assess their impact on marine biota.openCanesi, L; Ciacci, Caterina; Bergami, E; Monopoli, M. P; Dawson, K. A; Papa, Stefano; Canonico, Barbara; Corsi, I.Canesi, L; Ciacci, Caterina; Bergami, E; Monopoli, M. P; Dawson, K. A; Papa, Stefano; Canonico, Barbara; Corsi, I

Multifunctional halloysite and hectorite catalysts for effective transformation of biomass to biodiesel

Halloysite surface was modified with tetrabutylammonium iodide, and then the obtained nanomaterial was used as support for ZnO nanoparticles. After characterization, the nanomaterial was used as a catalyst for fatty acid methyl esters (FAMEs) production. The recyclability of the nanomaterial was also investigated, and the optimization of reaction conditions by the design of experiments approach was performed as well. In addition, the synthesized nanomaterial was tested as a catalyst for FAME production from a series of waste lipids affording biodiesel in moderate to good yields (35–95%), depending on the matrix. To fully exploit the feasibility of clay minerals as catalysts in biodiesel formation, a screening of different clays and clay minerals with different morphologies and compositions, such as sepiolite, palygorskite, bentonite, and hectorite was also performed in the esterification of FFAs (a mixture of 1:1 palmitic and stearic acids). Finally, hectorite, chosen as a model of 2:1 clay minerals, was covalently modified, and tested as a catalyst in the esterification of FFAs

Randomized clinical trial on short-time compression with Kaolin-filled pad: a new strategy to avoid early bleeding and subacute radial artery occlusion after percutaneous coronary intervention.

BACKGROUND: Despite the increasing use of transradial techniques for cardiac percutaneous procedures, none of the strategies commonly utilized for hemostasis has been able to reduce the occurrence of radial artery occlusion (RAO). The aim of this study was to evaluate the occurrence of 24-hour RAO and the rate of bleeding of a novel hemostatic device for radial closure after percutaneous interventions, in adjunct to short-time compression.METHODS: Once the radial access was obtained, patients were randomized to 3 different strategies of radial closure: a short compression with the QuikClot® Interventional™ pad (Z-Medica Corporation, Wallingford, CT, USA) (15 minutes, group 1), a short compression (15 minutes, group 2), and a conventional prolonged compression (2 hours, group 3) both without QuikClot® utilization.RESULTS: Fifty patients in group 1, 20 in group 2, and 50 in group 3 were enrolled. The three groups were homogenous for baseline and procedural characteristics. None of patients in group 1 developed RAO, 1 (5%) occurred in group 2, and 5 (10%) in group 3 (P = 0.05). Active bleeding after compression removal occurred in 10 patients (20%) in group 1, 18 (90%) in group 2, and 1 (2%) in group 3 (P < 0.001). Among patients in group 1, at univariate analysis, the predictors of acute bleeding resulted in chronic therapy with clopidogrel (Odds Ratio 28.78, 95% Confidence Intervals 4.79-172.82, P < 0.001) and high levels of activated clotting time (ACT) at the time of sheath removal (OR 1.02, 95% CI 1.00-1.03, P = 0.009). At ROC analysis, the cutoff value of ACT for the risk of bleeding with a sensitivity of 80% and specificity of 75% was 287 seconds.CONCLUSIONS: Early sheet removal and short-time compression with QuikClot® Interventional™ can reduce the rate of RAO after diagnostic or interventional procedures especially in patients not on double antiplatelet therapy

An environmentally benign antimicrobial nanoparticle based on a silver-infused lignin core

Silver nanoparticles have antibacterial properties, but their use has been a cause for concern because they persist in the environment. Here, we show that lignin nanoparticles infused with silver ions and coated with a cationic polyelectrolyte layer form a biodegradable and green alternative to silver nanoparticles. The polyelectrolyte layer promotes the adhesion of the particles to bacterial cell membranes and, together with silver ions, can kill a broad spectrum of bacteria, including Escherichia coli, Pseudomonas aeruginosa and quaternary-amine-resistant Ralstonia sp. Ion depletion studies have shown that the bioactivity of these nanoparticles is time-limited because of the desorption of silver ions. High-throughput bioactivity screening did not reveal increased toxicity of the particles when compared to an equivalent mass of metallic silver nanoparticles or silver nitrate solution. Our results demonstrate that the application of green chemistry principles may allow the synthesis of nanoparticles with biodegradable cores that have higher antimicrobial activity and smaller environmental impact than metallic silver nanoparticles

Dimensionality of Carbon Nanomaterials Determines the Binding and Dynamics of Amyloidogenic Peptides: Multiscale Theoretical Simulations

Experimental studies have demonstrated that nanoparticles can affect the rate of protein self-assembly, possibly interfering with the development of protein misfolding diseases such as Alzheimer's, Parkinson's and prion disease caused by aggregation and fibril formation of amyloid-prone proteins. We employ classical molecular dynamics simulations and large-scale density functional theory calculations to investigate the effects of nanomaterials on the structure, dynamics and binding of an amyloidogenic peptide apoC-II(60-70). We show that the binding affinity of this peptide to carbonaceous nanomaterials such as C60, nanotubes and graphene decreases with increasing nanoparticle curvature. Strong binding is facilitated by the large contact area available for π-stacking between the aromatic residues of the peptide and the extended surfaces of graphene and the nanotube. The highly curved fullerene surface exhibits reduced efficiency for π-stacking but promotes increased peptide dynamics. We postulate that the increase in conformational dynamics of the amyloid peptide can be unfavorable for the formation of fibril competent structures. In contrast, extended fibril forming peptide conformations are promoted by the nanotube and graphene surfaces which can provide a template for fibril-growth

Adenosine A2A receptor modulation of hippocampal CA3-CA1 synapse plasticity during associative learning in behaving mice

© 2009 Nature Publishing Group All rights reservedPrevious in vitro studies have characterized the electrophysiological and molecular signaling pathways of adenosine tonic modulation on long-lasting synaptic plasticity events, particularly for hippocampal long-term potentiation(LTP). However, it remains to be elucidated whether the long-term changes produced by endogenous adenosine in the efficiency of synapses are related to those required for learning and memory formation. Our goal was to understand how endogenous activation of adenosine excitatory A2A receptors modulates the associative learning evolution in conscious behaving mice. We have studied here the effects of the application of a highly selective A2A receptor antagonist, SCH58261, upon a well-known associative learning paradigm - classical eyeblink conditioning. We used a trace paradigm, with a tone as the conditioned stimulus (CS) and an electric shock presented to the supraorbital nerve as the unconditioned stimulus(US). A single electrical pulse was presented to the Schaffer collateral–commissural pathway to evoke field EPSPs (fEPSPs) in the pyramidal CA1 area during the CS–US interval. In vehicle-injected animals, there was a progressive increase in the percentage of conditioning responses (CRs) and in the slope of fEPSPs through conditioning sessions, an effect that was completely prevented (and lost) in SCH58261 (0.5 mg/kg, i.p.)-injected animals. Moreover, experimentally evoked LTP was impaired in SCH58261- injected mice. In conclusion, the endogenous activation of adenosine A2A receptors plays a pivotal effect on the associative learning process and its relevant hippocampal circuits, including activity-dependent changes at the CA3-CA1 synapse.This study was supported by grants from the Spanish Ministry of Education and Research (BFU2005-01024 and BFU2005-02512), Spanish Junta de Andalucía (BIO-122 and CVI-02487), and the Fundación Conocimiento y Cultura of the Pablo de Olavide University (Seville, Spain).B. Fontinha was in receipt of a studentship from a project grant (POCI/SAU-NEU/56332/2004) supported by Fundação para a Ciência e Tecnologia (FCT, Portugal), and of an STSM from Cost B30 concerted action of the EU

Identifying New Therapeutic Targets via Modulation of Protein Corona Formation by Engineered Nanoparticles

We introduce a promising methodology to identify new therapeutic targets in cancer. Proteins bind to nanoparticles to form a protein corona. We modulate this corona by using surface-engineered nanoparticles, and identify protein composition to provide insight into disease development.Using a family of structurally homologous nanoparticles we have investigated the changes in the protein corona around surface-functionalized gold nanoparticles (AuNPs) from normal and malignant ovarian cell lysates. Proteomics analysis using mass spectrometry identified hepatoma-derived growth factor (HDGF) that is found exclusively on positively charged AuNPs ((+)AuNPs) after incubation with the lysates. We confirmed expression of HDGF in various ovarian cancer cells and validated binding selectivity to (+)AuNPs by Western blot analysis. Silencing of HDGF by siRNA resulted s inhibition in proliferation of ovarian cancer cells.We investigated the modulation of protein corona around surface-functionalized gold nanoparticles as a promising approach to identify new therapeutic targets. The potential of our method for identifying therapeutic targets was demonstrated through silencing of HDGF by siRNA, which inhibited proliferation of ovarian cancer cells. This integrated proteomics, bioinformatics, and nanotechnology strategy demonstrates that protein corona identification can be used to discover novel therapeutic targets in cancer