Embryonic stem cells express multiple Eph-subfamily receptor tyrosine kinases.

Eph and its homologues form the largest subfamily of receptor tyrosine kinases. Normal expression patterns of this subfamily indicate roles in differentiation and development, whereas their overexpression has been linked to oncogenesis. This study investigated the potential role of Eph-related molecules during very early embryonic development by examining their expression in embryonic stem (ES) cells and embryoid bodies differentiated from ES cells in vitro. By use of a strategy based on reverse transcriptase-mediated PCR, nine clones containing Eph-subfamily sequence were isolated from ES cells. Of these, eight were almost identical to one of four previously identified molecules (Sek, Nuk, Eck, and Mek4). However, one clone contained sequence from a novel Eph-subfamily member, which was termed embryonic stem-cell kinase or Esk. Northern analysis showed expression of Esk in ES cells, embryoid bodies, day 12 mouse embryos, and some tissues of the adult animal. Levels of expression were similar in ES cells and embryoid bodies. By comparison, Mek4 showed no significant transcription in the ES cell cultures by Northern analysis, whereas Eck displayed stronger signals in ES cells than in the embryoid bodies. These results suggest that Eph-subfamily molecules may play roles during the earliest phases of embryogenesis. Furthermore, the relative importance of different members of this subfamily appears to change as development proceeds.

Multiple calcium channel transcripts in rat osteosarcoma cells: selective activation of alpha 1D isoform by parathyroid hormone.

Osteoblasts express calcium channels that are thought to be involved in the transduction of extracellular signals regulating bone metabolism. The molecular identity of the pore-forming subunit (alpha 1) of L-type calcium channel(s) was determined in rat osteosarcoma UMR-106 cells, which express an osteoblast phenotype. A homology-based reverse transcriptase-polymerase chain reaction cloning strategy was employed that used primers spanning the fourth domain. Three types of cDNAs were isolated, corresponding to the alpha 1S (skeletal), alpha 1C (cardiac), and alpha 1D (neuroendocrine) isoforms. In the transmembrane segment IVS3 and the extracellular loop formed by the IVS3-S4 linker, a single pattern of mRNA splicing was found that occurs in all three types of calcium channel transcripts. Northern blot analysis revealed an 8.6-kb mRNA that hybridized to the alpha 1C probe and 4.8- and 11.7-kb mRNAs that hybridized to the alpha 1S and alpha 1D probes. Antisense oligonucleotides directed to the calcium channel alpha 1D transcript, but not those directed to alpha 1S or alpha 1C transcripts, inhibited the rise of intracellular calcium induced by parathyroid hormone. However, alpha 1D antisense oligonucleotides had no effect on the accumulation of cAMP induced by parathyroid hormone. When L-type calcium channels were activated with Bay K 8644, antisense oligonucleotides to each of the three isoforms partially inhibited the rise of intracellular calcium. The present results provide evidence for the expression of three distinct calcium channel alpha 1-subunit isoforms in an osteoblast-like cell line. We conclude that the alpha 1D isoform is selectively activated by parathyroid hormone.

The Multiple Signaling Systems Regulating Virulence in Pseudomonas aeruginosa

Cell-to-cell communication is a major process that allows bacteria to sense and coordinately react to the fluctuating conditions of the surrounding environment. In several pathogens, this process triggers the production of virulence factors and/or a switch in bacterial lifestyle that is a major determining factor in the outcome and severity of the infection. Understanding how bacteria control these signaling systems is crucial to the development of novel antimicrobial agents capable of reducing virulence while allowing the immune system of the host to clear bacterial infection, an approach likely to reduce the selective pressures for development of resistance. We provide here an up-to-date overview of the molecular basis and physiological implications of cell-to-cell signaling systems in Gram-negative bacteria, focusing on the well-studied bacterium Pseudomonas aeruginosa. All of the known cell-to-cell signaling systems in this bacterium are described, from the most-studied systems, i.e., N-acyl homoserine lactones (AHLs), the 4-quinolones, the global activator of antibiotic and cyanide synthesis (GAC), the cyclic di-GMP (c-di-GMP) and cyclic AMP (cAMP) systems, and the alarmones guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), to less-well-studied signaling molecules, including diketopiperazines, fatty acids (diffusible signal factor [DSF]-like factors), pyoverdine, and pyocyanin. This overview clearly illustrates that bacterial communication is far more complex than initially thought and delivers a clear distinction between signals that are quorum sensing dependent and those relying on alternative factors for their production.

Multi-wavelength regeneration of phase encoded signals based on phase sensitive amplifiers

Future high capacity optical links will have to make use of frequent signal regeneration to enable long distance transmission. In this respect, the role of all-optical signal processing becomes increasingly important because of its potential to mitigate signal impairments at low cost and power consumption. More substantial benefits are expected if regeneration is achieved simultaneously on a multiple signal band. Until recently, this had been achieved only for on-off keying modulation formats. However, as in future transmission links the information will be encoded also in the phase for enhancing the spectral efficiency, novel subsystem concepts will be needed for multichannel processing of such advanced signal formats. In this paper we show that phase sensitive amplifiers can be an ideal technology platform for developing such regenerators and we discuss our recent demonstration of the first multi-channel regenerator for phase encoded signals.

Simultaneous multiple channel all-optical NRZ to CSRZ and RZ to CSRZ format conversion using an SOA-NOLM

The optical conversion bandwidth for an all-optical modulation format converter, based on a semiconductor laser amplifier in a nonlinear optical loop mirror (SOA-NOLM), is investigated. 4 Â 10 Gbit/s channels are all- optically converted between both non-return-to-zero (NRZ) and return-to-zero (RZ) format to carrier- suppressed return-to-zero (CSRZ). WDM transmission of the converted signals over a 194 km fibre span is then demonstrated. The receiver sensitivity for the converted four wavelengths is measured and compared after transmission.

Simultaneous multiple channel all-optical NRZ to CSRZ and RZ to CSRZ format conversion using an SOA-NOLM

The optical conversion bandwidth for an all-optical modulation format converter, based on a semiconductor laser amplifier in a nonlinear optical loop mirror (SOA-NOLM), is investigated. 4 Â 10 Gbit/s channels are all- optically converted between both non-return-to-zero (NRZ) and return-to-zero (RZ) format to carrier- suppressed return-to-zero (CSRZ). WDM transmission of the converted signals over a 194 km fibre span is then demonstrated. The receiver sensitivity for the converted four wavelengths is measured and compared after transmission.

Simultaneous multiple channel all-optical NRZ to CSRZ and RZ to CSRZ format conversion using an SOA-NOLM

The optical conversion bandwidth for an all-optical modulation format converter, based on a semiconductor laser amplifier in a nonlinear optical loop mirror (SOA-NOLM), is investigated. 4×10 Gbit/s channels are all-optically converted between both non-return-to-zero (NRZ) and return-to-zero (RZ) format to carrier-suppressed return-to-zero (CSRZ). WDM transmission of the converted signals over a 194 km fibre span is then demonstrated. The receiver sensitivity for the converted four wavelengths is measured and compared after transmission. © 2014 Elsevier B.V. All rights reserved.

Multi-wavelength regeneration of phase encoded signals based on phase sensitive amplifiers

Future high capacity optical links will have to make use of frequent signal regeneration to enable long distance transmission. In this respect, the role of all-optical signal processing becomes increasingly important because of its potential to mitigate signal impairments at low cost and power consumption. More substantial benefits are expected if regeneration is achieved simultaneously on a multiple signal band. Until recently, this had been achieved only for on-off keying modulation formats. However, as in future transmission links the information will be encoded also in the phase for enhancing the spectral efficiency, novel subsystem concepts will be needed for multichannel processing of such advanced signal formats. In this paper we show that phase sensitive amplifiers can be an ideal technology platform for developing such regenerators and we discuss our recent demonstration of the first multi-channel regenerator for phase encoded signals.

Direction Finding Estimators of Cyclostationary Signals in Array Processing for Microwave Power Transmission

A solar power satellite is paid attention to as a clean, inexhaustible large- scale base-load power supply. The following technology related to beam control is used: A pilot signal is sent from the power receiving site and after direction of arrival estimation the beam is directed back to the earth by same direction. A novel direction-finding algorithm based on linear prediction technique for exploiting cyclostationary statistical information (spatial and temporal) is explored. Many modulated communication signals exhibit a cyclostationarity (or periodic correlation) property, corresponding to the underlying periodicity arising from carrier frequencies or baud rates. The problem was solved by using both cyclic second-order statistics and cyclic higher-order statistics. By evaluating the corresponding cyclic statistics of the received data at certain cycle frequencies, we can extract the cyclic correlations of only signals with the same cycle frequency and null out the cyclic correlations of stationary additive noise and all other co-channel interferences with different cycle frequencies. Thus, the signal detection capability can be significantly improved. The proposed algorithms employ cyclic higher-order statistics of the array output and suppress additive Gaussian noise of unknown spectral content, even when the noise shares common cycle frequencies with the non-Gaussian signals of interest. The proposed method completely exploits temporal information (multiple lag ), and also can correctly estimate direction of arrival of desired signals by suppressing undesired signals. Our approach was generalized over direction of arrival estimation of cyclostationary coherent signals. In this paper, we propose a new approach for exploiting cyclostationarity that seems to be more advanced in comparison with the other existing direction finding algorithms.

Space division multiple access for wireless sensor networks

This dissertation proposed a self-organizing medium access control protocol (MAC) for wireless sensor networks (WSNs). The proposed MAC protocol, space division multiple access (SDMA), relies on sensor node position information and provides sensor nodes access to the wireless channel based on their spatial locations. SDMA divides a geographical area into space divisions, where there is one-to-one map between the space divisions and the time slots. Therefore, the MAC protocol requirement is the sensor node information of its position and a prior knowledge of the one-to-one mapping function. The scheme is scalable, self-maintaining, and self-starting. It provides collision-free access to the wireless channel for the sensor nodes thereby, guarantees delay-bounded communication in real time for delay sensitive applications. This work was divided into two parts: the first part involved the design of the mapping function to map the space divisions to the time slots. The mapping function is based on a uniform Latin square. A Uniform Latin square of order k = m 2 is an k x k square matrix that consists of k symbols from 0 to k-1 such that no symbol appears more than once in any row, in any column, or in any m x in area of main subsquares. The uniqueness of each symbol in the main subsquares presents very attractive characteristic in applying a uniform Latin square to time slot allocation problem in WSNs. The second part of this research involved designing a GPS free positioning system for position information. The system is called time and power based localization scheme (TPLS). TPLS is based on time difference of arrival (TDoA) and received signal strength (RSS) using radio frequency and ultrasonic signals to measure and detect the range differences from a sensor node to three anchor nodes. TPLS requires low computation overhead and no time synchronization, as the location estimation algorithm involved only a simple algebraic operation.

Peak -to -average power ratio reduced parallel interference cancellation Multicarrier-Code Division Multiple Access system with anti -interference property

Orthogonal Frequency-Division Multiplexing (OFDM) has been proved to be a promising technology that enables the transmission of higher data rate. Multicarrier Code-Division Multiple Access (MC-CDMA) is a transmission technique which combines the advantages of both OFDM and Code-Division Multiplexing Access (CDMA), so as to allow high transmission rates over severe time-dispersive multi-path channels without the need of a complex receiver implementation. Also MC-CDMA exploits frequency diversity via the different subcarriers, and therefore allows the high code rates systems to achieve good Bit Error Rate (BER) performances. Furthermore, the spreading in the frequency domain makes the time synchronization requirement much lower than traditional direct sequence CDMA schemes. There are still some problems when we use MC-CDMA. One is the high Peak-to-Average Power Ratio (PAPR) of the transmit signal. High PAPR leads to nonlinear distortion of the amplifier and results in inter-carrier self-interference plus out-of-band radiation. On the other hand, suppressing the Multiple Access Interference (MAI) is another crucial problem in the MC-CDMA system. Imperfect cross-correlation characteristics of the spreading codes and the multipath fading destroy the orthogonality among the users, and then cause MAI, which produces serious BER degradation in the system. Moreover, in uplink system the received signals at a base station are always asynchronous. This also destroys the orthogonality among the users, and hence, generates MAI which degrades the system performance. Besides those two problems, the interference should always be considered seriously for any communication system. In this dissertation, we design a novel MC-CDMA system, which has low PAPR and mitigated MAI. The new Semi-blind channel estimation and multi-user data detection based on Parallel Interference Cancellation (PIC) have been applied in the system. The Low Density Parity Codes (LDPC) has also been introduced into the system to improve the performance. Different interference models are analyzed in multi-carrier communication systems and then the effective interference suppression for MC-CDMA systems is employed in this dissertation. The experimental results indicate that our system not only significantly reduces the PAPR and MAI but also effectively suppresses the outside interference with low complexity. Finally, we present a practical cognitive application of the proposed system over the software defined radio platform.

Peak-to-Average Power Ratio Reduced Parallel Interference Cancellation Multicarrier-Code Division Multiple Access System with Anti-Interference Property

Orthogonal Frequency-Division Multiplexing (OFDM) has been proved to be a promising technology that enables the transmission of higher data rate. Multicarrier Code-Division Multiple Access (MC-CDMA) is a transmission technique which combines the advantages of both OFDM and Code-Division Multiplexing Access (CDMA), so as to allow high transmission rates over severe time-dispersive multi-path channels without the need of a complex receiver implementation. Also MC-CDMA exploits frequency diversity via the different subcarriers, and therefore allows the high code rates systems to achieve good Bit Error Rate (BER) performances. Furthermore, the spreading in the frequency domain makes the time synchronization requirement much lower than traditional direct sequence CDMA schemes. There are still some problems when we use MC-CDMA. One is the high Peak-to-Average Power Ratio (PAPR) of the transmit signal. High PAPR leads to nonlinear distortion of the amplifier and results in inter-carrier self-interference plus out-of-band radiation. On the other hand, suppressing the Multiple Access Interference (MAI) is another crucial problem in the MC-CDMA system. Imperfect cross-correlation characteristics of the spreading codes and the multipath fading destroy the orthogonality among the users, and then cause MAI, which produces serious BER degradation in the system. Moreover, in uplink system the received signals at a base station are always asynchronous. This also destroys the orthogonality among the users, and hence, generates MAI which degrades the system performance. Besides those two problems, the interference should always be considered seriously for any communication system. In this dissertation, we design a novel MC-CDMA system, which has low PAPR and mitigated MAI. The new Semi-blind channel estimation and multi-user data detection based on Parallel Interference Cancellation (PIC) have been applied in the system. The Low Density Parity Codes (LDPC) has also been introduced into the system to improve the performance. Different interference models are analyzed in multi-carrier communication systems and then the effective interference suppression for MC-CDMA systems is employed in this dissertation. The experimental results indicate that our system not only significantly reduces the PAPR and MAI but also effectively suppresses the outside interference with low complexity. Finally, we present a practical cognitive application of the proposed system over the software defined radio platform.

Subfornical organ neurons integrate cardiovascular and metabolic signals

The subfornical organ (SFO) is a critical circumventricular organ involved in the control of cardiovascular and metabolic homeostasis. Despite the abundant literature clearly demonstrating the ability of SFO neurons to sense and respond to a plethora of circulating signals that influence various physiological systems, investigation of how simultaneously sensed signals interact and are integrated in the SFO is lacking. In this study, we use patch clamp techniques to investigate how the traditionally classified ‘cardiovascular’ hormone angiotensin II (ANG), ‘metabolic’ hormone cholecystokinin (CCK) and ‘metabolic’ signal glucose interact and are integrated in the SFO. Sequential bath-application of CCK (10nM) and ANG (10nM) onto dissociated SFO neurons revealed that: 63% of responsive SFO neurons depolarized to both CCK & ANG; 25% depolarized to ANG only; and 12% hyperpolarized to CCK only. We next investigated the effects of glucose by incubating and recording neurons in either hypo-, normo- or hyperglycemic conditions for a minimum of 24 hours and comparing the proportions of responses to ANG (n=55) or CCK (n=83) application in each condition. A hyperglycemic environment was associated with a larger proportion of depolarizing responses to ANG (X2, p<0.05), and a smaller proportion of depolarizing responses along with a larger proportion of hyperpolarizing responses to CCK (X2, p<0.01). These data demonstrate that SFO neurons excited by CCK are also excited by ANG, suggesting that CCK may influence fluid intake or blood pressure via the SFO, complementary to the well-understood actions of ANG at this site. Additionally, the demonstration that glucose environment affects the responsiveness of neurons to both these hormones highlights the ability of SFO neurons to integrate multiple metabolic and cardiovascular signals to affect transmission of information from the circulation to the brain, which has important implications for this structure’s critical role regulation of autonomic function.

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk

Using electroencephalography signals to control acoustical processing

Current hearing-assistive technology performs poorly in noisy multi-talker conditions. The goal of this thesis was to establish the feasibility of using EEG to guide acoustic processing in such conditions. To attain this goal, this research developed a model via the constructive research method, relying on literature review. Several approaches have revealed improvements in the performance of hearing-assistive devices under multi-talker conditions, namely beamforming spatial filtering, model-based sparse coding shrinkage, and onset enhancement of the speech signal. Prior research has shown that electroencephalography (EEG) signals contain information that concerns whether the person is actively listening, what the listener is listening to, and where the attended sound source is. This thesis constructed a model for using EEG information to control beamforming, model-based sparse coding shrinkage, and onset enhancement of the speech signal. The purpose of this model is to propose a framework for using EEG signals to control sound processing to select a single talker in a noisy environment containing multiple talkers speaking simultaneously. On a theoretical level, the model showed that EEG can control acoustical processing. An analysis of the model identified a requirement for real-time processing and that the model inherits the computationally intensive properties of acoustical processing, although the model itself is low complexity placing a relatively small load on computational resources. A research priority is to develop a prototype that controls hearing-assistive devices with EEG. This thesis concludes highlighting challenges for future research.