Calibrated Continuous-Time Sigma-Delta Modulators

To provide more information mobility, many wireless communication systems such as WCDMA and EDGE in phone systems, bluetooth and WIMAX in communication networks have been recently developed. Recent efforts have been made to build the allin- one next generation device which integrates a large number of wireless services into a single receiving path in order to raise the competitiveness of the device. Among all the receiver architectures, the high-IF receiver presents several unique properties for the next generation receiver by digitalizing the signal at the intermediate frequency around a few hundred MHz. In this architecture, the modulation/demodulation schemes, protocols, equalization, etc., are all determined in a software platform that runs in the digital signal processor (DSP) or FPGA. The specifications for most of front-end building blocks are relaxed, except the analog-to-digital converter (ADC). The requirements of large bandwidth, high operational frequency and high resolution make the design of the ADC very challenging. Solving the bottleneck associated with the high-IF receiver architecture is a major focus of many ongoing research efforts. In this work, a 6th-order bandpass continuous time sigma-delta ADC with measured 68.4dB SNDR at 10MHz bandwidth to accommodate video applications is proposed. Tuned at 200 MHz, the fs/4 architecture employs an 800 MHz clock frequency. By making use of a unique software-based calibration scheme together with the tuning properties of the bandpass filters developed under the umbrella of this project, the ADC performance is optimized automatically to fulfill all requirements for the high-IF architecture. In a separate project, other critical design issues for continuous-time sigma-delta ADCs are addressed, especially the issues related to unit current source mismatches in multi-level DACs as well as excess loop delays that may cause loop instability. The reported solutions are revisited to find more efficient architectures. The aforementioned techniques are used for the design of a 25MHz bandwidth lowpass continuous-time sigma-delta modulator with time-domain two-step 3-bit quantizer and DAC for WiMAX applications. The prototype is designed by employing a level-to-pulse-width modulation (PWM) converter followed by a single-level DAC in the feedback path to translate the typical digital codes into PWM signals with the proposed pulse arrangement. Therefore, the non-linearity issue from current source mismatch in multi-level DACs is prevented. The jitter behavior and timing mismatch issue of the proposed time-based methods are fully analyzed. The measurement results of a chip prototype achieving 67.7dB peak SNDR and 78dB SFDR in 25MHz bandwidth properly demonstrate the design concepts and effectiveness of time-based quantization and feedback. Both continuous-time sigma-delta ADCs were fabricated in mainstream CMOS 0.18um technologies, which are the most popular in today?s consumer electronics industry

miR-221/222 promotes S-phase entry and cellular migration in control of basal-like breast cancer.

The miR-221/222 cluster has been demonstrated to function as oncomiR in human cancers. miR-221/222 promotes epithelial-to-mesenchymal transition (EMT) and confers tamoxifen resistance in breast cancer. However, the effects and mechanisms by which miR-221/222 regulates breast cancer aggressiveness remain unclear. Here we detected a much higher expression of miR-221/222 in highly invasive basal-like breast cancer (BLBC) cells than that in non-invasive luminal cells. A microRNA dataset from breast cancer patients indicated an elevated expression of miR-221/222 in BLBC subtype. S-phase entry of the cell cycle was associated with the induction of miR-221/222 expression. miRNA inhibitors specially targeting miR-221 or miR-222 both significantly suppressed cellular migration, invasion and G1/S transition of the cell cycle in BLBC cell types. Proteomic analysis demonstrated the down-regulation of two tumor suppressor genes, suppressor of cytokine signaling 1 (SOCS1) and cyclin-dependent kinase inhibit 1B (CDKN1B), by miR-221/222. This is the first report to reveal miR-221/222 regulation of G1/S transition of the cell cycle. These findings demonstrate that miR-221/222 contribute to the aggressiveness in control of BLBC

Intracellular mechanisms underlying the nicotinic enhancement of LTP in the rat dentate gyrus

We have previously shown that activation of nicotinic acetylcholine receptors (nAChRs) enhanced long-term potentiation (LTP) in the rat dentate gyrus in vitro via activation of α7 nAChR. In the present studies, mechanisms underlying the acute and chronic nicotinic enhancement of LTP were examined. In particular, the involvement of activation of intracellular kinases was examined using selective kinase antagonists, and the effects of enhancing cholinergic function with positive allosteric modulators of the α7 nAChR and with acetylcholinesterase (AChE) inhibitors were also investigated. Activation of extracellular signal-regulated kinase (ERK) and cAMP-dependent protein kinase (PKA) was found to be involved in the induction of the acute nicotinic enhancement of LTP, although not control LTP. In contrast, activation of the tyrosine kinase Src, Ca2+-calmodulin-dependent protein kinase II, Janus kinase 2 and p38 mitogen-activated protein kinase was not involved in the acute nicotinic enhancement of LTP, although Src activation was necessary for control LTP. Moreover, activation of phosphoinositide 3-kinase was involved in the acute nicotinic enhancement of LTP to a much lesser extent than in control LTP. Chronic nicotine enhancement of LTP was found to be dependent on PKA, ERK and Src kinases. Acute nicotinic enhancement of LTP was occluded by chronic nicotine treatment. The positive allosteric modulator PNU-120596 was found to strongly reduce the threshold for nicotinic enhancement of LTP, an affect mediated via the α7 nAChR as it was blocked by the selective antagonist methyllycaconitine. The AChE inhibitors tacrine and physostigmine enhanced control LTP

Evaluating indoor positioning systems in a shopping mall : the lessons learned from the IPIN 2018 competition

The Indoor Positioning and Indoor Navigation (IPIN) conference holds an annual competition in which indoor localization systems from different research groups worldwide are evaluated empirically. The objective of this competition is to establish a systematic evaluation methodology with rigorous metrics both for real-time (on-site) and post-processing (off-site) situations, in a realistic environment unfamiliar to the prototype developers. For the IPIN 2018 conference, this competition was held on September 22nd, 2018, in Atlantis, a large shopping mall in Nantes (France). Four competition tracks (two on-site and two off-site) were designed. They consisted of several 1 km routes traversing several floors of the mall. Along these paths, 180 points were topographically surveyed with a 10 cm accuracy, to serve as ground truth landmarks, combining theodolite measurements, differential global navigation satellite system (GNSS) and 3D scanner systems. 34 teams effectively competed. The accuracy score corresponds to the third quartile (75th percentile) of an error metric that combines the horizontal positioning error and the floor detection. The best results for the on-site tracks showed an accuracy score of 11.70 m (Track 1) and 5.50 m (Track 2), while the best results for the off-site tracks showed an accuracy score of 0.90 m (Track 3) and 1.30 m (Track 4). These results showed that it is possible to obtain high accuracy indoor positioning solutions in large, realistic environments using wearable light-weight sensors without deploying any beacon. This paper describes the organization work of the tracks, analyzes the methodology used to quantify the results, reviews the lessons learned from the competition and discusses its future

Bithiazole: An Intriguing Electron-Deficient Building for Plastic Electronic Applications.

The heterocyclic thiazole unit has been extensively used as electron-deficient building block in π-conjugated materials over the last decade. Its incorporation into organic semiconducting materials is particularly interesting due to its structural resemblance to the more commonly used thiophene building block, thus allowing the optoelectronic properties of a material to be tuned without significantly perturbing its molecular structure. Here, we discuss the structural differences between thiazole- and thiophene-based organic semiconductors, and the effects on the physical properties of the materials. An overview of thiazole-based polymers is provided, which have emerged over the past decade for organic electronic applications and it is discussed how the incorporation of thiazole has affected the device performance of organic solar cells and organic field-effect transistors. Finally, in conclusion, an outlook is presented on how thiazole-based polymers can be incorporated into all-electron deficient polymers in order to obtain high-performance acceptor polymers for use in bulk-heterojunction solar cells and as organic field-effect transistors. Computational methods are used to discuss some newly designed acceptor building blocks that have the potential to be polymerized with a fused bithiazole moiety, hence propelling the advancement of air-stable n-type organic semiconductors

An in vitro spinal cord injury model to screen neuroregenerative materials

Implantable 'structural bridges' based on nanofabricated polymer scaffolds have great promise to aid spinal cord regeneration. Their development (optimal formulations, surface functionalizations, safety, topographical influences and degradation profiles) is heavily reliant on live animal injury models. These have several disadvantages including invasive surgical procedures, ethical issues, high animal usage, technical complexity and expense. In vitro 3-D organotypic slice arrays could offer a solution to overcome these challenges, but their utility for nanomaterials testing is undetermined. We have developed an in vitro model of spinal cord injury that replicates stereotypical cellular responses to neurological injury in vivo, viz. reactive gliosis, microglial infiltration and limited nerve fibre outgrowth. We describe a facile method to safely incorporate aligned, poly-lactic acid nanofibre meshes (±poly-lysine + laminin coating) within injury sites using a lightweight construct. Patterns of nanotopography induced outgrowth/alignment of astrocytes and neurons in the in vitro model were strikingly similar to that induced by comparable materials in related studies in vivo. This highlights the value of our model in providing biologically-relevant readouts of the regeneration-promoting capacity of synthetic bridges within the complex environment of spinal cord lesions. Our approach can serve as a prototype to develop versatile bio-screening systems to identify materials/combinatorial strategies for regenerative medicine, whilst reducing live animal experimentation.EPSRC Doctoral Training Centre in regenerative medicine (EP/F500491/1

Follicular dendritic cells help establish follicle identity and promote B cell retention in germinal centers

Selective ablation of follicular dendritic cells in mice results in disorganization of primary follicles and dispersal of B cells out of splenic germinal centers

Identification by Automated Screening of a Small Molecule that Selectively Eliminates Neural Stem Cells Derived from hESCs but Not Dopamine Neurons

BACKGROUND:We have previously described fundamental differences in the biology of stem cells as compared to other dividing cell populations. We reasoned therefore that a differential screen using US Food and Drug Administration (FDA)-approved compounds may identify either selective survival factors or specific toxins and may be useful for the therapeutically-driven manufacturing of cells in vitro and possibly in vivo. METHODOLOGY/PRINCIPAL FINDINGS:In this study we report on optimized methods for feeder-free culture of hESCs and hESC-derived neural stem cells (NSCs) to facilitate automated screening. We show that we are able to measure ATP as an indicator of metabolic activity in an automated screening assay. With this optimized platform we screened a collection of FDA-approved drugs to identify compounds that have differential toxicity to hESCs and their neural derivatives. Nine compounds were identified to be specifically toxic for NSCs to a greater extent than for hESCs. Six of these initial hits were retested and verified by large-scale cell culture to determine dose-responsive NSC toxicity. One of the compounds retested, amiodarone HCL, was further tested for possible effects on postmitotic neurons, a likely target for transplant therapy. Amiodarone HCL was found to be selectively toxic to NSCs but not to differentiated neurons or glial cells. Treated and untreated NSCs and neurons were then interrogated with global gene expression analysis to explore the mechanisms of action of amiodarone HCl. The gene expression analysis suggests that activation of cell-type specific cationic channels may underlie the toxicity of the drug. CONCLUSIONS/SIGNIFICANCE:In conclusion, we have developed a screening strategy that allows us to rapidly identify clinically approved drugs for use in a Chemistry, Manufacture and Control protocol that can be safely used to deplete unwanted contaminating precursor cells from a differentiated cell product. Our results also suggest that such a strategy is rich in the potential of identifying lineage specific reagents and provides additional evidence for the utility of stem cells in screening and discovery paradigms