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

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

Non

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

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)

Neanderthal at the south-easternmost edge: the spread of Levallois Mousterian in the Indian Subcontinent

Description of the Middle Palaeolithic, Levalloisian, Mousterian assemblages from the western banks of the Indus, in Lower Sindh (Pakistan) and considerations on the south-easternmore distribution of the Neanderthal Levalloisian assemblage

Technological choices and lithic production in the Indus period: Case studies from Sindh (Pakistan) Paolo Biagi

The Indus Civilisation flourished in part of the Indian Subcontinent during the Bronze Age. It was a complex urban civilisation, with a writing system, still undeciphered. It is also famous for its sophisticated handicrafts, painted pottery, stoneware, steatite and semiprecious beads, faience and metalwork, which were traded to long distances across the Persian Gulf and the Arabian Sea. Nevertheless chipped stone technology and flint artefacts production still represented important aspects of the economic system, especially in connection with specialised craft productions, which led to an intensive exploitation of the flint raw material sources of the Rohri Hills, in Upper Sindh. Here thousands of flint mines were exploited for a mass production of blades and bladelets, which were later transformed into sophisticated micro-drill points in the craft activity areas of the cities, where they are found in association with semiprecious stone bead making workshops. This paper analyses the complexity of the lithic production of the Indus Civilisation. It describes the technology and methods of production of such blades, according to the evidence collected during several years of research carried out in the Rohri Hills. Here, besides the mines, a good number of flint knapping workshops were excavated by the Italo-Pakistani expedition. The analytical study of the lithic assemblages recovered from these excavations and the experimental reproduction of the debitage sequence, favoured the reconstruction of the techniques and the methods of the Indus flint working