Effect of β-amyloid block of the fast-inactivating K+ channel on intracellular Ca2+ and excitability in a modeled neuron

β-Amyloid peptide (Aβ), one of the primary protein components of senile plaques found in Alzheimer disease, is believed to be toxic to neurons by a mechanism that may involve loss of intracellular calcium regulation. We have previously shown that Aβ blocks the fast-inactivating potassium (A) current. In this work, we show, through the use of a mathematical model, that the Aβ-mediated block of the A current could result in increased intracellular calcium levels and increased membrane excitability, both of which have been observed in vitro upon acute exposure to Aβ. Simulation results are compared with experimental data from the literature; the simulations quantitatively capture the observed concentration dependence of the neuronal response and the level of increase in intracellular calcium.

Small viscosity asymptotics for the inertial range of local structure and for the wall region of wall-bounded turbulent shear flow.

The small viscosity asymptotics of the inertial range of local structure and of the wall region in wallbounded turbulent shear flow are compared. The comparison leads to a sharpening of the dichotomy between Reynolds number dependent scaling (power-type) laws and the universal Reynolds number independent logarithmic law in wall turbulence. It further leads to a quantitative prediction of an essential difference between them, which is confirmed by the results of a recent experimental investigation. These results lend support to recent work on the zero viscosity limit of the inertial range in turbulence.

The cell wall components peptidoglycan and lipoteichoic acid from Staphylococcus aureus act in synergy to cause shock and multiple organ failure.

Although the incidence of Gram-positive sepsis has risen strongly, it is unclear how Gram-positive organisms (without endotoxin) initiate septic shock. We investigated whether two cell wall components from Staphylococcus aureus, peptidoglycan (PepG) and lipoteichoic acid (LTA), can induce the inflammatory response and multiple organ dysfunction syndrome (MODS) associated with septic shock caused by Gram-positive organisms. In cultured macrophages, LTA (10 micrograms/ml), but not PepG (100 micrograms/ml), induces the release of nitric oxide measured as nitrite. PepG, however, caused a 4-fold increase in the production of nitrite elicited by LTA. Furthermore, PepG antibodies inhibited the release of nitrite elicited by killed S. aureus. Administration of both PepG (10 mg/kg; i.v.) and LTA (3 mg/kg; i.v.) in anesthetized rats resulted in the release of tumor necrosis factor alpha and interferon gamma and MODS, as indicated by a decrease in arterial oxygen pressure (lung) and an increase in plasma concentrations of bilirubin and alanine aminotransferase (liver), creatinine and urea (kidney), lipase (pancreas), and creatine kinase (heart or skeletal muscle). There was also the expression of inducible nitric oxide synthase in these organs, circulatory failure, and 50% mortality. These effects were not observed after administration of PepG or LTA alone. Even a high dose of LTA (10 mg/kg) causes only circulatory failure but no MODS. Thus, our results demonstrate that the two bacterial wall components, PepG and LTA, work together to cause systemic inflammation and multiple systems failure associated with Gram-positive organisms.

Inhibition of nuclear vesicle fusion by antibodies that block activation of inositol 1,4,5-trisphosphate receptors.

Inositol 1,4,5-trisphosphate (IP3) receptors are ligand-gated channels that release intracellular Ca2+ stores in response to the second messenger, IP3. We investigated the potential role of IP3 receptors during nuclear envelope assembly in vitro, using Xenopus egg extracts. Previous work suggested that Ca2+ mobilization is required for nuclear vesicle fusion and implicated IP3 receptor activity. To test the involvement of IP3 receptors using selective reagents, we obtained three distinct polyclonal antibodies to the type 1 IP3 receptor. Pretreatment of membranes with two of the antibodies inhibited IP3-stimulated CA2+ release in vitro and also inhibited nuclear vesicle fusion. One inhibitory serum was directed against 420 residues within the "coupling" domain, which includes several potential regulatory sites. The other inhibitory serum was directed against 95 residues near the C terminus and identifies an inhibitory epitope(s) in this region. The antibodies had no effect on receptor affinity for IP3. Because nuclear vesicle fusion was inhibited by antibodies that block Ca2+ flux, but not by control and preimmune antibodies, we concluded that the activation of IP3 receptors is required for fusion. The signal that activates the channel during fusion is unknown.

Microenvironment and microvascular wall modulate cancer cell progression

Tumour progression is a complex process that frequently brings to cancer metastasis, the first cause of poor prognosis of cancer affected patients. Metastasis are generated by cells escaped from a primary mass and able to enter in the circulation, survive and proliferate in a new, distant site of the organism. To reach all these goal, many different phenomena had occur within both the cancer cells and the surrounding microenvironment. In the first part of this thesis, the focus was pointed on the metastatic potential of a leiomyosarcoma cell model. The studied cancer cells demonstrated a strong invasive capacity of the ECM in vitro, principally by production of matrix metalloproteinases 2 and 9, and robust pro-angiogenic activity in the chick CAM model, that facilitate its dissemination through same chick embryo internal organs. This study, with the title “MMPs and angiogenesis affect the metastatic potential of a human vulvar leiomyosarcoma cell line”, is presented in the published form. In the second part of this work, the emphasis was given to the microvascular element of the tumour microenvironment and specifically to the perivascular pericytes. These are intriguing cells due to their uncertain involvement in the biology of cancer. It is not clear how pericytes change within the tumour microenvironment and which is their contribute during the tumour dissemination. After the characterization of the chosen pericytic cell model, an in vitro study of the interaction between pericytes and different cancer cell lines where performed. Indirect and direct cell-cell interaction as well as movement of cancer cells in presence of pericytes conditioned media was analysed, in order to investigate the reciprocal influence of pericytes and tumour cells in the context of cancer progression.

Tecnologia construtiva de fachada em chapas delgadas estruturadas em light steel framing.

Aumento da produtividade, melhorias na qualidade dos produtos, redução de custos e de impactos ambientais são essenciais para a capacidade competitiva das empresas. A execução da fachada faz parte do caminho crítico da obra, por ser um subsistema que associa as funções de fechamento, acabamento, iluminação e ventilação e ainda por incorporar sistemas prediais; apresenta, por isso também, um alto custo direto em relação aos outros subsistemas do edifício. A tecnologia construtiva de fachadas em chapas delgadas com estrutura em Light Steel Framing (LSF) é uma alternativa viável para aumentar a produtividade e reduzir os prazos de obra, com qualidade e desempenho, e pode trazer benefícios em relação a atividades intensas em mão de obra como é o caso da alvenaria de vedação e de seus revestimentos. O presente trabalho tem por objetivo sistematizar e analisar o conhecimento relativo a essa tecnologia construtiva de fachada. O método adotado compreende revisão bibliográfica. Como contribuição, o trabalho reúne um conjunto organizado de informações sobre os principais sistemas disponíveis no mercado contemplando: a caracterização do sistema de fachada, de suas camadas e dos perfis leves de aço e a sistematização das principais avaliações técnicas de sistemas existentes em outros países, reunindo normas técnicas de produtos e de execução. Acredita-se que a reunião e organização das informações, antes dispersas em diversas referências, têm potencial para subsidiar o meio técnico para tomada de decisão quanto ao uso adequado da nova tecnologia.

A public key cryptosystem based on block upper triangular matrices

We propose a public key cryptosystem based on block upper triangular matrices. This system is a variant of the Discrete Logarithm Problem with elements in a finite group, capable of increasing the difficulty of the problem while maintaining the key size. We also propose a key exchange protocol that guarantees that both parties share a secret element of this group and a digital signature scheme that provides data authenticity and integrity.

Dynamic investigation of an ancient masonry bell tower with operational modal analysis: a non-destructive experimental technique to obtain the dynamic characteristics of a structure

This paper shows the results of an experimental analysis on the bell tower of “Chiesa della Maddalena” (Mola di Bari, Italy), to better understand the structural behavior of slender masonry structures. The research aims to calibrate a numerical model by means of the Operational Modal Analysis (OMA) method. In this way realistic conclusions about the dynamic behavior of the structure are obtained. The choice of using an OMA derives from the necessity to know the modal parameters of a structure with a non-destructive testing, especially in case of cultural-historical value structures. Therefore by means of an easy and accurate process, it is possible to acquire in-situ environmental vibrations. The data collected are very important to estimate the mode shapes, the natural frequencies and the damping ratios of the structure. To analyze the data obtained from the monitoring, the Peak Picking method has been applied to the Fast Fourier Transforms (FFT) of the signals in order to identify the values of the effective natural frequencies and damping factors of the structure. The main frequencies and the damping ratios have been determined from measurements at some relevant locations. The responses have been then extrapolated and extended to the entire tower through a 3-D Finite Element Model. In this way, knowing the modes of vibration, it has been possible to understand the overall dynamic behavior of the structure.

Single wall carbon nanotubes loaded with Pd and NiPd nanoparticles for H2 sensing at room temperature

Pd and bimetallic Ni50Pd50 nanoparticles protected by polyvinylpyrrolidone (PVP) have been synthesized by the reduction-by-solvent method and deposited on single wall carbon nanotubes (SWCNTs) to be tested as H2 sensors. The SWCNTs were deposited by drop casting from different suspensions. The Pd nanoparticles-based sensors show a very reproducible performance with good sensitivity and very low response times (few seconds) for different H2 concentrations, ranging from 0.2% to 5% vol. H2 in air at atmospheric pressure. The influence of the metal nanoparticle composition, the quality of SWCNTs suspension and the metal loading have been studied, observing that all these parameters play an important role in the H2 sensor performance. Evidence for water formation during the H2 detection on Pd nanoparticles has been found, and its repercussion on the behaviour of the assembled sensors is discussed. The sensor preparation procedure detailed in this work has proven to be simple and reproducible to prepare cost-effective and highly efficient H2 sensors that perform very well under real application conditions.

Seismic behavior of a masonry chimney with severe cracking condition: preliminary study

This paper presents a structural analysis of a masonry chimney built in the 1940s, which is currently being cataloged as local interest heritage. This structure has not served any industrial purpose for the last thirty years. The chimney is located in the town of Agost (Alicante - Spain) and directly exposed to the prevailing winds from the sea, as it is approximately 12 km away from the waterfront and there are not any significant barriers, which could protect the structure against the wind. There are longitudinal cracks and fissures all along the shaft because of the chimney’s geometrical characteristics, the effect of the masonry creep and especially the lack of maintenance. Moreover, there is also a permanent bending deformation in the upper 1/3 of the height due to the wind pressure. A numerical analysis for the static behavior against gravity and wind loads was performed using the structure’s current conditions after a detailed report of its geometry, its construction system and the cracking pattern. Afterwards, the dynamic behavior was studied, i.e. a seismic analysis using both response spectra and accelerograms in order to examine the structural stability. This work shows the pre-monitoring analysis before any experimental testing. Using the current results the future test conditions will be determined (e.g. number of sensors and monitoring point location, excitation systems, etc) prior to a possible structural reinforcement by applying composite material (fiber reinforced polymers).

Optimal model through identified frequencies of a masonry building structure with wooden floors

The paper presents the analysis of an important historical building: the Saint James Theater in the city of Corfù (Greece) actually used as the Municipality House. The building, located in the center of the city, is made of carves stones and is characterized by a stocky shape and by the presence of wooden floors. The study deals with the structural identification of such structure through the analysis of its ambient vibrations recorded by means of accelerometers with high accuracy. A full dynamic testing was developed using ambient vibrations to identify the main modal parameters and to make a non-destructive characterization of this building. The results of these dynamic tests are compared with the modal analysis of a complex finite element (FE) simulation of the structure. This analysis may present several problems and uncertainties for this stocky building. Due to the presence of wooden floors, the local modes can be highly excited and, as a consequence, the evaluation of the structural modal parameters presents some difficulties.

Electrochemical behaviour of different redox probes on single wall carbon nanotube buckypaper-modified electrodes

In the present work, the electrochemical properties of single-walled carbon nanotube buckypapers (BPs) were examined in terms of carbon nanotubes nature and preparation conditions. The performance of the different free-standing single wall carbon nanotube sheets was evaluated via cyclic voltammetry of several redox probes in aqueous electrolyte. Significant differences are observed in the electron transfer kinetics of the buckypaper-modified electrodes for both the outer- and inner-sphere redox systems. These differences can be ascribed to the nature of the carbon nanotubes (nanotube diameter, chirality and aspect ratio), surface oxidation degree and type of functionalities. In the case of dopamine, ferrocene/ferrocenium, and quinone/hydroquinone redox systems the voltammetric response should be thought as a complex contribution of different tips and sidewall domains which act as mediators for the electron transfer between the adsorbate species and the molecules in solution. In the other redox systems only nanotube ends are active sites for the electron transfer. It is also interesting to point out that a higher electroactive surface area not always lead to an improvement in the electron transfer rate of various redox systems. In addition, the current densities produced by the redox reactions studied here are high enough to ensure a proper electrochemical signal, which enables the use of BPs in sensing devices.

A first approach to earthquake damage estimation in Haiti: advices to minimize the seismic risk

This study is in the frame of the cooperative line that several Spanish Universities and other foreign partners started with the Haitian government in 2010. According to our studies (Benito et al. in An evaluation of seismic hazard in La Hispaniola, after the 2010 Haiti earthquake, 33rd General Assembly of the European Seismological Commission, Moscow, Russia, 2012) and recent scientific literature, the earthquake hazard in Haiti remains high (Calais et al. in Nat Geosci 3:794–799, 2010). In view of this, we wonder whether the country is currently ready to face another earthquake. In this sense, we estimated several damage scenarios in Port-au-Prince and Cap-Haitien associated to realistic possible major earthquakes. Our findings show that almost 50 % of the building stock of both cities would result uninhabitable due to structural damage. Around 80 % of the buildings in both cities have reinforced concrete structure with concrete block infill; however, the presence of masonry buildings becomes significant (between 25 and 45 % of the reinforced concrete buildings) in rural areas and informal settlements on the outskirts, where the estimated damage is higher. The influence of the soil effect on the damage spatial distribution is evident in both cities. We have found that the percentage of uninhabitable buildings in soft soil areas may be double the percentage obtained in nearby districts located in hard soil. These results reveal that a new seismic catastrophe of similar or even greater consequences than the 2010 Haiti earthquake might happen if the earthquake resilience is not improved in the country. Nowadays, the design of prevention actions and mitigation policies is the best instrument the society has to face seismic risk. In this sense, the results of this research might contribute to define measures oriented to earthquake risk reduction in Haiti, which should be a real priority for national and international institutions.

Tom Johnson and John Ghindia block for Don Peterson vs Purdue, UM Football, 1949

[Tom Johnson, #76, John Ghindia, #23, Don Peterson, #23]