lHuman cytotoxic T lymphocytes with reduced sensitivity to Fas-induced apoptosis

Effector-memory T cells expressing Fas (Apo-1/CD95) are switched to an apoptotic program by cross-linking with Fas-ligand (FasL). Consequently, tumors that express FasL can induce apoptosis of infiltrating Fas-positive T lymphocytes and subdue any antitumor host immune response. Since Epstein-Barr virus (EBV)-associated tumors such as Hodgkin lymphoma (HL) and nasopharyngeal carcinoma (NPC) express FasL, we determined whether EBV-specific cytotoxic T lymphocytes (EBV-CTLs) could be modified to resist this evasion strategy. We show that long-term down-modulation of Fas can be achieved in EBV-CTLs by transduction with small interfering RNA (siRNA) encoded in a retrovirus. Modified T cells resisted Fas/FasL-mediated apoptosis compared with control cells and showed minimal cleavage of the caspase3 substrate poly(ADP-ribose) polymerase (PARP) protein after Fas engagement. Prolonged Fas stimulation selected a uniformly Fas(low) and FasL resistant population. Removal of responsiveness to this single death signal had no other discernible effects on EBV-CTLs. In particular, it did not lead to their autonomous growth since the modified EBV-CTLs remained polyclonal, and their survival and proliferation retained dependence on antigen-specific stimulation and on the presence of other physiologic growth signals. EBV-CTLs with knocked down Fas should have a selective functional and survival advantage over unmodified EBV-CTLs in the presence of tumors expressing FasL and may be of value for adoptive cellular therapy. (c) 2005 by The American Society of Hematology

The Prehistoric Fishers and Gatherers of the Northern and Western Coasts of the Arabian Sea

This chapter is a review of the prehistory of the fisher-gatherers who settled along the coasts of the Arabian Sea and the Gulf of Oman. Previous research and studies have been centred mainly on the western coasts of the Indian Ocean. They have presented and discussed the general patterns and chronological frame of the coastal human adaptation since the early Holocene, and the recurrent presence of shell middens located close to mangrove environments. More recent research has been focussed on the northern shores of the Arabian Sea. From this region we have new evidence of the presence of fisher-gatherers communities that seasonally settled along the ancient coastline and islands of south-western Sindh and Las Bela (Balochistan) since the end of the eighth millennium BP indicating that early navigation already took place in that period. According to the archaeological evidence, the subsistence activities of these human groups were varied though seasonally based mainly on fishing and shellfish gathering. Broadly speaking marine and mangrove resources were widespread exploited along the two coasts of the Arabian Sea during favourable, well-defined periods of coastal adaptation following the varied environmental conditions and sea-level changes that took place since the beginning of the Holocene

A fixed combination of probiotics and herbal extracts attenuates intestinal barrier dysfunction from inflammatory stress in an in vitro model using Caco-2 cells.

Background: Inflammatory Bowel Diseases (IBD), are considered a growing global disease, with about ten million people being affected worldwide. Maintenance of intestinal barrier integrity is crucial for preventing IBD onset and exacerbations. Some recent patents regarding oily formulations containing probiotics (WO2010122107A1 and WO2010103374A9) and the use of probiotics for gastrointestinal complaints (US20110110905A1 and US9057112B2) exist, or are pending application. Objective: In this work, we studied the effect of a fixed combination of registered Lactobacillus reuteri and Lactobacillus acidophilus strains and herbal extracts in an in vitro inflammation experimental model. Methods: Caco-2 cell monolayer was exposed to INF-\u3b3+TNF-\u3b1 or to LPS; Trans Epithelial Electrical Resistance (TEER) and paracellular permeability were investigated. ZO-1 and occludin Tight Junctions (TJs) were also investigated by mean of immunofluorescence. Results: Pre-treatment with the fixed combination of probiotics and herbal extracts prevented the inflammation-induced TEER decrease, paracellular permeability increase and TJs translocation. Conclusions: In summary, the fixed combination of probiotics and herbal extracts investigated in this research was found to be an interesting candidate for targeting the re-establishment of intestinal barrier function in IBD conditions

Hard macrocells for DC/DC converter in automotive embedded mechatronic systems

A novel configurable DC/DC converter architecture, to be integrated as hard macrocell in automotive embedded systems, is proposed in the paper. It aims at realizing an intelligent voltage regulator. With respect to the state of the art, the challenge is the integration into an automotive-qualified chip of several advanced features like dithering of switching frequency, nested control loops with both current and voltage feedback, asynchronous hysteretic control for low power mode, slope control of the power FET gate driver, and diagnostic block against out-of-range current or voltage or temperature conditions. Moreover, the converter macrocell can be connected to the in-vehicle digital network, exchanging with the main vehicle control unit status/diagnostic flags and commands. The proposed design can be configured to work both in step-up and step-down modes, to face a very wide operating input voltage range from 2.5 to 60 V and absolute range from −0.3 to 70 V. The main target is regulating all voltages required in the emerging hybrid/electric vehicles where, besides the conventional 12 V DC bus, also a 48 V DC bus is present. The proposed design supports also digital configurability of the output regulated voltage, through a programmable divider, and of the coefficients of the proportional-integrative controller inside the nested control loops. Fabricated in 0.35 μm CMOS technology, experimental measurements prove that the IC can operate in harsh automotive environments since it meets stringent requirements in terms of electrostatic discharge (ESD) protection, operating temperature range, out-of-range current, or voltage condition

Conservative non-surgical management of horizontal root-fractured maxillary incisors in a young male with angle class ii, division 2, malocclusion

Horizontal root fractures are a rare emergency in a dental office. The injury involves periodontal ligament, cementum, dentine and pulp. The healing is influenced by the location of the root fracture, the displacement of the fragments and the status of the pulp. This report presents a clinical case of horizontal fractures to both maxillary central incisors due to an act of violence. The type of occlusion has avoided a severe diastasis of the coronal parts with a subsequent damage to the pulp and periodontum. The fractures were treated with an orthodontic splint without any further therapy and hard tissue healing was observed. A careful diagnosis and well-timed treatment planning usually allow a cost-efficient and biologically-oriented therapy with a favorable outcome

A Competitive Approach for Designing Multi-Antenna Cognitive Access Networks

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Modeling brain connectivity dynamics in functional Magnetic Resonance Imaging via Particle Filtering

Interest in the studying of functional connections in the brain has grown considerably in the last decades, as many studies have pointed out that alterations in the interaction among brain areas can play a role as markers of neurological diseases. Most studies in this field treat the brain network as a system of connections stationary in time, but dynamic features of brain connectivity can provide useful information, both on physiology and pathological conditions of the brain. In this paper, we propose the application of a computational methodology, named Particle Filter (PF), to study non-stationarities in brain connectivity in functional Magnetic Resonance Imaging (fMRI). The PF algorithm estimates time-varying hidden parameters of a first-order linear time-varying Vector Autoregressive model (VAR) through a Sequential Monte Carlo strategy. On simulated time series, the PF approach effectively detected and enabled to follow time-varying hidden parameters and it captured causal relationships among signals. The method was also applied to real fMRI data, acquired in presence of periodic tactile or visual stimulations, in different sessions. On these data, the PF estimates were consistent with current knowledge on brain functioning. Most importantly, the approach enabled to detect statistically significant modulations in the cause-effect relationship between brain areas, which correlated with the underlying visual stimulation pattern presented during the acquisition

Experimental studies on the progressive collapse of building structures: A review and discussion on dynamic column removal techniques

Dynamic progressive collapse tests are becoming more and more popular in recent years since this approach captures the real structural behavior more robustly, and progressive collapse response more accurately. The results of dynamic tests are of great importance for defining computational models and improving current codes and guidelines. Even for static tests and simulations, the dynamic effects should be indirectly considered, namely by including the dynamic amplification factors. The adopted dynamic column removal approach is the most important and challenging aspect of the dynamic progressive collapse tests. While several methods for dynamic column removal have already been suggested and implemented, a comprehensive discussion of the techniques is missing. In this regard, a comprehensive review of the available literature is first presented. Current experimental techniques for dynamic column removal are categorized into three main groups, i.e., quick-release device, dummy column, and explosion technique, and the underlying concepts and applied methodologies are compared and contrasted. Finally, future needs are highlighted and possible improvements for the current methodologies are also discussed

foF2 seismo-ionospheric effect analysis: actual data and numerical simulations

Abstract. On the background of seasonal and helio-geomagnetic disturbances, disturbances of the ionization density near noon connected to earthquakes are investigated. The study is performed for some tens of earthquakes with magnitudes M>5 and depths h<70 km, which occur at distances from the vertical sounding stations "Tokyo", "Akita", and "Yamagawa" not larger than R=exp(M)+150 km. The analysis is performed using data registered by the three sounding stations every hour during 30 years. Especially methods of the statistical analysis are applied to search for regularities in the lithospheric-ionospheric links before and after earthquakes. The growth of the mean ionization density N at the F-layer electron density maximum Fof2 five-three days before earthquakes, and the decrease of N approaching the eruption and during a few days after the earthquake is investigated in dependence on both the magnitude of the earthquake M and the ionization density N near the F-layer maximum. It is found that some days before earthquakes the decrease of the ionization density ΔN is proportional to the values of M and N. After the earthquakes, ΔN depends much weaker on the magnitude M, and it is not influenced by the ionization density N. The variations of the ionization density three days before earthquakes do not depend on N and M (within the same order of approximation)