Inflammation and TCR Signal Strength Determine the Breadth of the T Cell Response in a Bim-Dependent Manner.

Generating a diverse T cell memory population through vaccination is a promising strategy to overcome pathogen epitope variability and tolerance to tumor Ags. The effector and memory pool becomes broad in TCR diversity by recruiting high- and low-affinity T cells. We wanted to determine which factors dictate whether a memory T cell pool has a broad versus focused repertoire. We find that inflammation increases the magnitude of low- and high-affinity T cell responses equally well, arguing against a synergistic effect of TCR and inflammatory signals on T cell expansion. We dissect the differential effects of TCR signal strength and inflammation and demonstrate that they control effector T cell survival in a bim-dependent manner. Importantly, bim-dependent cell death is overcome with a high Ag dose in the context of an inflammatory environment. Our data define the framework for the generation of a broad T cell memory pool to inform future vaccine design.

IL-12-mediated STAT4 signaling and TCR signal strength cooperate in the induction of CD40L in human and mouse CD8(+) T cells.

CD40L is one of the key molecules bridging the activation of specific T cells and the maturation of professional and nonprofessional antigen-presenting cells including B cells. CD4(+) T cells have been regarded as the major T-cell subset that expresses CD40L upon cognate activation; however, we demonstrate here that a putative CD8(+) helper T-cell subset expressing CD40L is induced in human and murine CD8(+) T cells in vitro and in mice immunized with antigen-pulsed dendritic cells. IL-12 and STAT4-mediated signaling was the major instructive cytokine signal boosting the ability of CD8(+) T cells to express CD40L both in vitro and in vivo. Additionally, TCR signaling strength modulated CD40L expression in CD8(+) T cells after primary differentiation in vitro as well as in vivo. The induction of CD40L in CD8(+) T cells regulated by IL-12 and TCR signaling may enable CD8(+) T cells to respond autonomously of CD4(+) T cells. Thus, we propose that under proinflammatory conditions, a self-sustaining positive feedback loop could facilitate the efficient priming of T cells stimulated by high affinity peptide displaying APCs.

Single cell tuning of Myc expression by antigen receptor signal strength and interleukin-2 in T lymphocytes.

Myc controls the metabolic reprogramming that supports effector T cell differentiation. The expression of Myc is regulated by the T cell antigen receptor (TCR) and pro-inflammatory cytokines such as interleukin-2 (IL-2). We now show that the TCR is a digital switch for Myc mRNA and protein expression that allows the strength of the antigen stimulus to determine the frequency of T cells that express Myc. IL-2 signalling strength also directs Myc expression but in an analogue process that fine-tunes Myc quantity in individual cells via post-transcriptional control of Myc protein. Fine-tuning Myc matters and is possible as Myc protein has a very short half-life in T cells due to its constant phosphorylation by glycogen synthase kinase 3 (GSK3) and subsequent proteasomal degradation. We show that Myc only accumulates in T cells exhibiting high levels of amino acid uptake allowing T cells to match Myc expression to biosynthetic demands. The combination of digital and analogue processes allows tight control of Myc expression at the population and single cell level during immune responses.

Anomalous variation of thermal lens signal with concentration from rhodamine B in methanol solution

Thermal lens signals in solutions of rhodamine B laser dye in methanol are measured using the dual beam pump-probe technique. The nature of variations of signal strength with concentration is found to be different for 514 and 488 nm Ar + laser excitations. However, both the pump wavelengths produce an oscillatory type variation of thermal lens signal amplitude with the concentration of the dye solution. Probable reasons for this peculiar behaviour (which is absent in the case of fluorescent intensity) are mentioned.

Changes in a nanoparticle's spectroscopic signal mediated by the local environment

Using a first-principles theoretical model the adsorption of a methyl radical on different sized silver nanoparticles is compared to the adsorption of the same radical on model surfaces. Calculations of our structural, dynamical and electronic properties indicated that small changes in the local environment will lead to small changes in infrared (IR) wavenumbers, but in dramatic changes in the IR signal. Our calculations indicate the lower the adsorption site coordination, the higher is the signal strength, suggesting that small changes in the electronic charge distribution will result in bigger changes in the polarizability and hence in the spectroscopic signal intensity. This effect explains, among others, the signal magnification observed for nanoparticles in surface enhanced Raman spectroscopic (SERS) experiments.

A Time-based Passive Source Localization System for Narrow-band Signal

Time-based indoor localization has been investigated for several years but the accuracy of existing solutions is limited by several factors, e.g., imperfect synchronization, signal bandwidth and indoor environment. In this paper, we compare two time-based localization algorithms for narrow-band signals, i.e., multilateration and fingerprinting. First, we develop a new Linear Least Square (LLS) algorithm for Differential Time Difference Of Arrival (DTDOA). Second, fingerprinting is among the most successful approaches used for indoor localization and typically relies on the collection of measurements on signal strength over the area of interest. We propose an alternative by constructing fingerprints of fine-grained time information of the radio signal. We offer comprehensive analytical discussions on the feasibility of the approaches, which are backed up by evaluations in a software defined radio based IEEE 802.15.4 testbed. Our work contributes to research on localization with narrow-band signals. The results show that our proposed DTDOA-based LLS algorithm obviously improves the localization accuracy compared to traditional TDOA-based LLS algorithm but the accuracy is still limited because of the complex indoor environment. Furthermore, we show that time-based fingerprinting is a promising alternative to power-based fingerprinting.

Rectangular room dimensions estimation using narrowband signal and sectorized antennas

A system for estimation of unknown rectangular room dimensions based on two radio transceivers, both capable of full duplex operations, is presented. The approach is based on CIR measurements taken at the same place where the signal is transmitted (generated), commonly known as self- to-self CIR. Another novelty is the receiver antenna design which consists of eight sectorized antennas with 45° aperture in the horizontal plane, whose total coverage corresponds to the isotropic one. The dimensions of a rectangular room are reconstructed directly from radio impulse responses by extracting the information regarding features like round trip time, received signal strength and reverberation time. Using radar approach the estimation of walls and corners positions are derived. Additionally, the analysis of the absorption coefficient of the test environment is conducted and a typical coefficient for office room with furniture is proposed. Its accuracy is confirmed through the results of volume estimation. Tests using measured data were performed, and the simulation results confirm the feasibility of the approach.

Haptic teleoperation of mobile robots for augmentation of operator perception in environments with low-wireless signal

Wireless teleoperation of field robots for maintenance, inspection and rescue missions is often performed in environments with low wireless connectivity, caused by signal losses from the environment and distance from the wireless transmitters. Various studies from the literature have addressed these problems with time-delay robust control systems and multi-hop wireless relay networks. However, such approaches do not solve the issue of how to present wireless data to the operator to avoid losing control of the robot. Despite the fact that teleoperation for maintenance often already involves haptic devices, no studies look at the possibility of using this existing feedback to aid operators in navigating within areas of variable wireless connectivity. We propose a method to incorporate haptic information into the velocity control of an omnidirectional robot to augment the operators perception of wireless signal strength in the remote environment. In this paper we introduce a mapping between wireless signal strength from multiple receivers to the force feedback of a 6 Degree of Freedom haptic master and evaluate the proposed approach using experimental data and randomly generated wireless maps

Effect of Disease Severity on the Performance of Cirrus Spectral-Domain OCT for Glaucoma Diagnosis

PURPOSE. To evaluate the effect of disease severity on the diagnostic accuracy of the Cirrus Optical Coherence Tomograph (Cirrus HD-OCT; Carl Zeiss Meditec, Inc., Dublin, CA) for glaucoma detection. METHODS. One hundred thirty-five glaucomatous eyes of 99 patients and 79 normal eyes of 47 control subjects were recruited from the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS). The severity of the disease was graded based on the visual field index (VFI) from standard automated perimetry. Imaging of the retinal nerve fiber layer (RNFL) was obtained using the optic disc cube protocol available on the Cirrus HD-OCT. Pooled receiver operating characteristic (ROC) curves were initially obtained for each parameter of the Cirrus HD-OCT. The effect of disease severity on diagnostic performance was evaluated by fitting an ROC regression model, with VFI used as a covariate, and calculating the area under the ROC curve (AUCs) for different levels of disease severity. RESULTS. The largest pooled AUCs were for average thickness (0.892), inferior quadrant thickness (0.881), and superior quadrant thickness (0.874). Disease severity had a significant influence on the detection of glaucoma. For the average RNFL thickness parameter, AUCs were 0.962, 0.932, 0.886, and 0.822 for VFIs of 70%, 80%, 90%, and 100%, respectively. CONCLUSIONS. Disease severity had a significant effect on the diagnostic performance of the Cirrus HD-OCT and thus should be considered when interpreting results from this device and when considering the potential applications of this instrument for diagnosing glaucoma in the various clinical settings. (Invest Ophthalmol Vis Sci. 2010;51:4104-4109) DOI:10.1167/iovs.094716

Human GC-AG alternative intron isoforms with weak donor sites show enhanced consensus at acceptor exon positions

It has been previously observed that the intrinsically weak variant GC donor sites, in order to be recognized by the U2-type spliceosome, possess strong consensus sequences maximized for base pair formation with U1 and U5/U6 snRNAs. However, variability in signal strength is a fundamental mechanism for splice site selection in alternative splicing. Here we report human alternative GC-AG introns (for the first time from any species), and show that while constitutive GC-AG introns do possess strong signals at their donor sites, a large subset of alternative GC-AG introns possess weak consensus sequences at their donor sites. Surprisingly, this subset of alternative isoforms shows strong consensus at acceptor exon positions 1 and 2. The improved consensus at the acceptor exon can facilitate a strong interaction with U5 snRNA, which tethers the two exons for ligation during the second step of splicing. Further, these isoforms nearly always possess alternative acceptor sites and always possess alternative acceptor sites and exhibit particularly weak polypyrimidine tracts characteristic of AG-dependent introns. The acceptor exon nucleotides are part of the consensus required for the U2AF(35)-mediated recognition of AG in such introns. Such improved consensus at acceptor exons is not found in either normal or alternative GT-AG introns having weak donor sites or weak polypyrimidine,tracts. The changes probably reflect mechanisms that allow GC-AG alternative intron isoforms to cope with two conflicting requirements, namely an apparent need for differential splice strength to direct the choice of alternative sites and a need for improved donor signals to compensate for the central mismatch base pair (C-A) in the RNA duplex of U1 snRNA and the pre-mRNA. The other important findings include (i) one in every twenty alternative introns is a GC-AG intron, and (ii) three of every five observed GC-AG introns are alternative isoforms.

A Platform to Emulate Ambient Assisted Living Environments

According to the opinion of clinicians, emerging medical conditions can be timely detected by observing changes in the activities of daily living and/or in the physiological signals of a person. To accomplish such purpose, it is necessary to properly monitor both the person’s physiological signals as well as the home environment with sensing technology. Wireless sensor networks (WSNs) are a promising technology for this support. After receiving the data from the sensor nodes, a computer processes the data and extracts information to detect any abnormality. The computer runs algorithms that should have been previously developed and tested in real homes or in living-labs. However, these installations (and volunteers) may not be easily available. In order to get around that difficulty, this paper suggests the making of a physical model to emulate basic actions of a user at home, thus giving autonomy to researchers wanting to test the performance of their algorithms. This paper also studies some data communication issues in mobile WSNs namely how the orientation of the sensor nodes in the body affects the received signal strength, as well as retransmission aspects of a TDMA-based MAC protocol in the data recovery process.

Avaliação dos sistemas WiMAX e GSM-R para ambientes ferroviários

Com este trabalho pretende-se estudar o desempenho das tecnologias GSM-R e WiMAX em ambientes ferroviários. Este tipo de estudo tem uma importância elevada devido grande interesse na reestruturação dos sistemas de comunicações vocacionados para aplicações ferroviárias. Estes sistemas são cada vez mais complexos, apresentando níveis mais elevados de exigência, como a segurança, suporte de sinalização, tráfego ferroviário e interoperabilidade entre sistemas de diferentes países. Com tudo isto é necessário explorar e conhecer o comportamento de diversas tecnologias para este tipo de aplicações. Neste trabalho foi efectuado um primeiro estudo abrangendo a tecnologia WiMAX (Norma IEEE 802.16d) em ambientes interiores de edifícios, de forma a estudar o seu comportamento com e sem linha de vista e em proximidade e afastamento da estação base. Este estudo foi conclusivo quanto há não adequação desta tecnologia em ambientes ferroviários, visto ter sido observado que em situações de ausência de linha de vista a degradação da qualidade do sinal não conseguiria suportar os níveis de exigência necessários para a aplicação do mesmo em ambientes ferroviários. Analisou-se em segundo lugar a tecnologia GSM-R, onde se efectuou um estudo de campo em ambientes reais. Para o estudo desta tecnologia foram utilizados ambientes diversificados de forma a obter um estudo mais aprofundado do seu comportamento. Como objectivo têm-se a criação de melhores métodos de planeamento, mais vocacionados para as características específicas dos ambientes ferroviários e exigências das aplicações dos sistemas de comunicações ferroviários. Através deste estudo foi possível obter conclusões relativamente à variação da potência do sinal para as diversas condições e ambientes de propagação a que o sistema GSM-R foi sujeito, tendo sido possível também caracterizar o tipo de ambientes característicos das linhas ferroviárias. Foi possível também concluir que este tipo de sistemas consegue responder aos níveis de exigência e aplicações dos sistemas de comunicação ferroviários, trazendo uma mais-valia relativamente aos existentes actualmente a nível nacional.

BANMAC: an opportunistic MAC protocol for reliable communications in body area networks

We consider reliable communications in Body Area Networks (BAN), where a set of nodes placed on human body are connected using wireless links. In order to keep the Specific Absorption Rate (SAR) as low as possible for health safety reasons, these networks operate in low transmit power regime, which however, is known to be error prone. It has been observed that the fluctuations of the Received Signal Strength (RSS) at the nodes of a BAN on a moving person show certain regularities and that the magnitude of these fluctuations are significant (5 - 20 dB). In this paper, we present BANMAC, a MAC protocol that monitors and predicts the channel fluctuations and schedules transmissions opportunistically when the RSS is likely to be higher. The MAC protocol is capable of providing differentiated service and resolves co-channel interference in the event of multiple co-located BANs in a vicinity. We report the design and implementation details of BANMAC integrated with the IEEE 802.15.4 protocol stack. We present experimental data which show that the packet loss rate (PLR) of BANMAC is significantly lower as compared to that of the IEEE 802.15.4 MAC. For comparable PLR, the power consumption of BANMAC is also significantly lower than that of the IEEE 802.15.4. For co-located networks, the convergence time to find a conflict-free channel allocation was approximately 1 s for the centralized coordination mechanism and was approximately 4 s for the distributed coordination mechanism.