Revisiting sodium and water reabsorption with functional genomics tools.

PURPOSE OF REVIEW: The kidney plays an essential role in maintaining sodium and water balance, thereby controlling the volume and osmolarity of the extracellular body fluids, the blood volume and the blood pressure. The final adjustment of sodium and water reabsorption in the kidney takes place in cells of the distal part of the nephron in which a set of apical and basolateral transporters participate in vectorial sodium and water transport from the tubular lumen to the interstitium and, finally, to the general circulation. According to a current model, the activity and/or cell-surface expression of these transporters is/are under the control of a gene network composed of the hormonally regulated, as well as constitutively expressed, genes. It is proposed that this gene network may include new candidate genes for salt- and water-losing syndromes and for salt-sensitive hypertension. A new generation of functional genomics techniques have recently been applied to the characterization of this gene network. The purpose of this review is to summarize these studies and to discuss the potential of the different techniques for characterization of the renal transcriptome. RECENT FINDINGS: Recently, DNA microarrays and serial analysis of gene expression have been applied to characterize the kidney transcriptome in different in-vivo and in-vitro models. In these studies, a set of new interesting genes potentially involved in the regulation of sodium and water reabsorption by the kidney have been identified and are currently under detailed investigation. SUMMARY: Characterization of the kidney transcriptome is greatly expanding our knowledge of the gene networks involved in multiple kidney functions, including the maintenance of sodium and water homeostasis.

The Wnt receptor FZD1 mediates chemoresistance in neuroblastoma through activation of the Wnt/beta-catenin pathway.

The development of chemoresistance represents a major obstacle in the successful treatment of cancers such as neuroblastoma (NB), a particularly aggressive childhood solid tumour. The mechanisms underlying the chemoresistant phenotype in NB were addressed by gene expression profiling of two doxorubicin (DoxR)-resistant vs sensitive parental cell lines. Not surprisingly, the MDR1 gene was included in the identified upregulated genes, although the highest overexpressed transcript in both cell lines was the frizzled-1 Wnt receptor (FZD1) gene, an essential component of the Wnt/beta-catenin pathway. FZD1 upregulation in resistant variants was shown to mediate sustained activation of the Wnt/beta-catenin pathway as revealed by nuclear beta-catenin translocation and target genes transactivation. Interestingly, specific micro-adapted short hairpin RNA (shRNAmir)-mediated FZD1 silencing induced parallel strong decrease in the expression of MDR1, another beta-catenin target gene, revealing a complex, Wnt/beta-catenin-mediated implication of FZD1 in chemoresistance. The significant restoration of drug sensitivity in FZD1-silenced cells confirmed the FZD1-associated chemoresistance. RNA samples from 21 patient tumours (diagnosis and postchemotherapy), showed a highly significant FZD1 and/or MDR1 overexpression after treatment, underlining a role for FZD1-mediated Wnt/beta-catenin pathway in clinical chemoresistance. Our data represent the first implication of the Wnt/beta-catenin pathway in NB chemoresistance and identify potential new targets to treat aggressive and resistant NB.

Access to Recovery Iowa: Provider Manual, October 2014

Access to Recovery - Iowa (ATR) is a three year grant awarded to the Iowa Department of Public Health (IDPH) by the Substance Abuse and Mental Health Services Administration, Center for Substance Abuse Treatment (SAMHSA) in October 2014. ATR provides funding to individuals to purchase services and supports linked to their recovery from substance abuse. ATR emphasizes client choice and increases the array of available community-based services, supports, and providers.

The CD4-like molecule LAG-3, biology and therapeutic applications.

IMPORTANCE OF THE FIELD: Promising immunotherapeutic agents targeting co-stimulatory pathways are currently being tested in clinical trials. One player in this array of regulatory pathways is the LAG-3/MHC class II axis. The lymphocyte activation gene-3 (LAG-3) is a negative co-stimulatory receptor that modulates T cell homeostasis, proliferation and activation. A recombinant soluble dimeric form of LAG-3 (sLAG-3-Ig, IMP321) shows adjuvant properties and enhances immunogenicity of tumor vaccines. Recent clinical trials produced encouraging results, especially when the human dimeric soluble form of LAG-3 (hLAG-3-Ig) was used in combination with chemotherapy. AREAS COVERED IN THIS REVIEW: The biological relevance of LAG-3 in vivo. Pre-clinical data demonstrating adjuvant properties, as well as the improvement of tumor immunity by sLAG-3-Ig. Recent advances in the clinical development of the therapeutic reagent IMP321, hLAG-3-Ig, for cancer treatment. WHAT THE READER WILL GAIN: This review summarizes preclinical and clinical data on the biological functions of LAG-3. TAKE HOME MESSAGE: The LAG-3 inhibitory pathway is attracting attention, in the light of recent studies demonstrating its role in T cell unresponsiveness, and Treg function after chronic antigen stimulation. As a soluble recombinant dimer, the sLAG-3-Ig protein acts as an adjuvant for therapeutic induction of T cell responses, and may be beneficial to cancer patients when used in combination therapies.

A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer.

To better understand the relationship between tumor-host interactions and the efficacy of chemotherapy, we have developed an analytical approach to quantify several biological processes observed in gene expression data sets. We tested the approach on tumor biopsies from individuals with estrogen receptor-negative breast cancer treated with chemotherapy. We report that increased stromal gene expression predicts resistance to preoperative chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide (FEC) in subjects in the EORTC 10994/BIG 00-01 trial. The predictive value of the stromal signature was successfully validated in two independent cohorts of subjects who received chemotherapy but not in an untreated control group, indicating that the signature is predictive rather than prognostic. The genes in the signature are expressed in reactive stroma, according to reanalysis of data from microdissected breast tumor samples. These findings identify a previously undescribed resistance mechanism to FEC treatment and suggest that antistromal agents may offer new ways to overcome resistance to chemotherapy.

A two-dimensional doppler-radiometer for earth observation

Compared to synthetic aperture radars (SARs), the angular resolution of microwave radiometers is quite poor. Traditionally, it has been limited by the physical size of the antenna. However, the angular resolution can be improved by means of aperture synthesis interferometric techniques. A narrow beam is synthesized during the image formation processing of the cross-correlations measured at zero-lag between pairs of signals collected by an array of antennas. The angular resolution is then determined by the maximum antenna spacing normalized to the wavelength (baseline). The next step in improving the angular resolution is the Doppler-Radiometer, somehow related to the super-synthesis radiometers and the Radiometer-SAR. This paper presents the concept of a three-antenna Doppler-Radiometer for 2D imaging. The performance of this instrument is evaluated in terms of angular/spatial resolution and radiometric sensitivity, and an L-band illustrative example is presented.

High-SNR analytical performance of spatial multiplexing MIMO systems with CSI

In this paper, we investigate the average andoutage performance of spatial multiplexing multiple-input multiple-output (MIMO) systems with channel state information at both sides of the link. Such systems result, for example, from exploiting the channel eigenmodes in multiantenna systems. Dueto the complexity of obtaining the exact expression for the average bit error rate (BER) and the outage probability, we deriveapproximations in the high signal-to-noise ratio (SNR) regime assuming an uncorrelated Rayleigh flat-fading channel. Moreexactly, capitalizing on previous work by Wang and Giannakis, the average BER and outage probability versus SNR curves ofspatial multiplexing MIMO systems are characterized in terms of two key parameters: the array gain and the diversity gain. Finally, these results are applied to analyze the performance of a variety of linear MIMO transceiver designs available in the literature.

Spatial filtering for pilot-aided WCDMA systems: a semi-blind subspace approach

This paper proposes a spatial filtering technique forthe reception of pilot-aided multirate multicode direct-sequencecode division multiple access (DS/CDMA) systems such as widebandCDMA (WCDMA). These systems introduce a code-multiplexedpilot sequence that can be used for the estimation of thefilter weights, but the presence of the traffic signal (transmittedat the same time as the pilot sequence) corrupts that estimationand degrades the performance of the filter significantly. This iscaused by the fact that although the traffic and pilot signals areusually designed to be orthogonal, the frequency selectivity of thechannel degrades this orthogonality at hte receiving end. Here,we propose a semi-blind technique that eliminates the self-noisecaused by the code-multiplexing of the pilot. We derive analyticallythe asymptotic performance of both the training-only andthe semi-blind techniques and compare them with the actual simulatedperformance. It is shown, both analytically and via simulation,that high gains can be achieved with respect to training-onlybasedtechniques.

Embedded Monitoring Server

This study investigates, designs, and implements an inexpensive application that allows local and remote monitoring of a home. The application consists of an array of sensors for monitoring different conditions in a home environment and also for accessing the devices that might be connected to the system. Only a few sensors are initially involved in this study and information about the temperature level, forced entry detection, smoke and water leakage detection can be obtained at any time from any location with an Internet connection. The application software (coded in C language) runs on an embedded system which is basically a wireless Linksys router running on a GNU/Linux based firmware for embedded systems. Interaction between the sensors and the application software is achieved through an implemented sensor interfacing circuit. The communication with the sensor interfacing unit is done through the serial port, and accessibility of the connected sensors is achieved through a telnet client. The sensors can be accessed from local and remote locations with the sensors giving reliable information. The resulting application shows that it is possible to use the router for other applications other than what it is intended for.

Enhanced MDIR receiver for space-time dispersive channels

A particular property of the matched desiredimpulse response receiver is introduced in this paper, namely,the fact that full exploitation of the diversity is obtained withmultiple beamformers when the channel is spatially and timelydispersive. This particularity makes the receiver specially suitablefor mobile and underwater communications. The new structureprovides better performance than conventional and weightedVRAKE receivers, and a diversity gain with no needs of additionalradio frequency equipment. The baseband hardware neededfor this new receiver may be obtained through reconfigurabilityof the RAKE architectures available at the base station. Theproposed receiver is tested through simulations assuming UTRAfrequency-division-duplexing mode.

The IST METRA Project

This article summarizes the main achievementsof the Multi-Element Transmit andReceive Antennas (METRA) Project, an ISTresearch and technological development project carried out between January 2000 and June 2001 by Universitat Politècnica de Catalunya, the Center for Personkommunikation of Aalborg University, Nokia Networks, Nokia Mobile Phones, and Vodafone Group Research and Development.The main objective of METRA was the performanceevaluation of multi-antenna terminals incombination with adaptive antennas at the basestation in UMTS communication systems. 1 AMIMO channel sounder was developed that providedrealistic multi-antenna channel measurements.Using these measured data, stochasticchannel models were developed and properly validated.These models were also evaluated inorder to estimate their corresponding channelcapacity. Different MIMO configurations andprocessing schemes were developed for both theFDD and TDD modes of UTRA, and their linkperformance was assessed. Performance evaluationwas completed by system simulations thatillustrated the benefits of MIMO configurationsto the network operator. Implementation cost vs.performance improvement was also covered bythe project, including the base station and terminalmanufacturer and network operator viewpoints.Finally, significant standards contributionswere generated by the project and presented to the pertinent 3GPP working groups.

Conditional maximum likelihood timing recovery: estimators and bounds

This paper is concerned with the derivation of new estimators and performance bounds for the problem of timing estimation of (linearly) digitally modulated signals. The conditional maximum likelihood (CML) method is adopted, in contrast to the classical low-SNR unconditional ML (UML) formulationthat is systematically applied in the literature for the derivationof non-data-aided (NDA) timing-error-detectors (TEDs). A new CML TED is derived and proved to be self-noise free, in contrast to the conventional low-SNR-UML TED. In addition, the paper provides a derivation of the conditional Cramér–Rao Bound (CRB ), which is higher (less optimistic) than the modified CRB (MCRB)[which is only reached by decision-directed (DD) methods]. It is shown that the CRB is a lower bound on the asymptotic statisticalaccuracy of the set of consistent estimators that are quadratic with respect to the received signal. Although the obtained boundis not general, it applies to most NDA synchronizers proposed in the literature. A closed-form expression of the conditional CRBis obtained, and numerical results confirm that the CML TED attains the new bound for moderate to high Eg/No.

Smart antennas in software radio base stations

The application of adaptive antenna techniques to fixed-architecture base stations has been shown to offer wide-ranging benefits, including interference rejection capabilities or increased coverage and spectral efficiency.Unfortunately, the actual implementation ofthese techniques to mobile communication scenarios has traditionally been set back by two fundamental reasons. On one hand, the lack of flexibility of current transceiver architectures does not allow for the introduction of advanced add-on functionalities. On the other hand, theoften oversimplified models for the spatiotemporal characteristics of the radio communications channel generally give rise toperformance predictions that are, in practice, too optimistic. The advent of software radio architectures represents a big step toward theintroduction of advanced receive/transmitcapabilities. Thanks to their inherent flexibilityand robustness, software radio architecturesare the appropriate enabling technology for theimplementation of array processing techniques.Moreover, given the exponential progression ofcommunication standards in coexistence andtheir constant evolution, software reconfigurabilitywill probably soon become the only costefficientalternative for the transceiverupgrade. This article analyzes the requirementsfor the introduction of software radio techniquesand array processing architectures inmultistandard scenarios. It basically summarizesthe conclusions and results obtained withinthe ACTS project SUNBEAM,1 proposingalgorithms and analyzing the feasibility ofimplementation of innovative and softwarereconfigurablearray processing architectures inmultistandard settings.

Robust beamforming for interference rejection in mobile communications

The problem of robust beamformer design for mobile communicationsapplications in the presence of moving co-channel sources isaddressed. A generalization of the optimum beamformer based on a statisticalmodel accounting for source movement is proposed. The new methodis easily implemented and is shown to offer dramatic improvements overconventional optimum beamforming for moving sources under a varietyof operating conditions.

Statistical reference criteria for adaptive signal processing in digital communications

A general criterion for the design of adaptive systemsin digital communications called the statistical reference criterionis proposed. The criterion is based on imposition of the probabilitydensity function of the signal of interest at the outputof the adaptive system, with its application to the scenario ofhighly powerful interferers being the main focus of this paper.The knowledge of the pdf of the wanted signal is used as adiscriminator between signals so that interferers with differingdistributions are rejected by the algorithm. Its performance isstudied over a range of scenarios. Equations for gradient-basedcoefficient updates are derived, and the relationship with otherexisting algorithms like the minimum variance and the Wienercriterion are examined.