Post-Transcriptional Regulation of BCL2 mRNA by the RNA-Binding Protein ZFP36L1 in Malignant B Cells

The human ZFP36 zinc finger protein family consists of ZFP36, ZFP36L1, and ZFP36L2. These proteins regulate various cellular processes, including cell apoptosis, by binding to adenine uridine rich elements in the 3′ untranslated regions of sets of target mRNAs to promote their degradation. The pro-apoptotic and other functions of ZFP36 family members have been implicated in the pathogenesis of lymphoid malignancies. To identify candidate mRNAs that are targeted in the pro-apoptotic response by ZFP36L1, we reverse-engineered a gene regulatory network for all three ZFP36 family members using the ‘maximum information coefficient’ (MIC) for target gene inference on a large microarray gene expression dataset representing cells of diverse histological origin. Of the three inferred ZFP36L1 mRNA targets that were identified, we focussed on experimental validation of mRNA for the pro-survival protein, BCL2, as a target for ZFP36L1. RNA electrophoretic mobility shift assay experiments revealed that ZFP36L1 interacted with the BCL2 adenine uridine rich element. In murine BCL1 leukemia cells stably transduced with a ZFP36L1 ShRNA lentiviral construct, BCL2 mRNA degradation was significantly delayed compared to control lentiviral expressing cells and ZFP36L1 knockdown in different cell types (BCL1, ACHN, Ramos), resulted in increased levels of BCL2 mRNA levels compared to control cells. 3′ untranslated region luciferase reporter assays in HEK293T cells showed that wild type but not zinc finger mutant ZFP36L1 protein was able to downregulate a BCL2 construct containing the BCL2 adenine uridine rich element and removal of the adenine uridine rich core from the BCL2 3′ untranslated region in the reporter construct significantly reduced the ability of ZFP36L1 to mediate this effect. Taken together, our data are consistent with ZFP36L1 interacting with and mediating degradation of BCL2 mRNA as an important target through which ZFP36L1 mediates its pro-apoptotic effects in malignant B-cells.

Compact high linearity switchable dual-mode microstrip bandpass filters

A compact highly linear microstrip dual-mode electronically switchable filter is presented. The key characteristics of the dual-mode switchable filter are investigated and described. A second order filter design procedure is outlined to facilitate the realisation of Butterworth and Chebyshev functions. The proposed filter was built and tested with NXP pin diode model BAP65-03. The measured and simulated results are in good agreement. The measured insertion loss in the ON state was 3.0 dB the isolation in the OFF state was 45 dB at the centre frequency. An evaluation of filter distortion is presented for digitally modulated 16 QAM and QPSK signals.

Dual-tracking multi-constellation GNSS front-end for high-performance receiver applications

This paper presents the design and implementation of a dual–tracking Radio Frequency (RF) front–end for a multi–constellation Global Navigation Satellite Systems (GNSS) receiver. The RF frond–end is based on the direct RF conversion architecture, which employs sub–Nyquist sampling (also known as subsampling) at RF. The dual–tracking RF front–end is composed of a few RF components that are duplicated to form the two RF channels. Employing a dual–channel Analogue–to–Digital Converter (ADC) enables synchronisation of the RF channels and minimises the errors resulting from the differences in the satellite clocks and the propagation delay between the two RF channels. The digitised GNSS signals are processed by two separate acquisition and tracking engines that are driven by the front–end’s master clock. This setup provides two synchronised receivers that are integrated onto one piece of hardware. The hardware is intended to be used for research applications such as multipath mitigation, scintillation assessment, and advanced satellite clock and spatial frame transformation modelling.

Smart City-Regional Governance: A 'Dual Transition'

This paper introduces the concept of ‘dual transition’ in relation to the notion of ‘smartness’ in city-regional governance. This consists of two intersecting dimensions, a broader change in political-economic and societal circumstances which surround city-regions, and a more detailed, local change towards ‘smartness’ in policy practices. Although ‘smart’ seems to have become a somewhat ubiquitous adjective in urban policy, it seeks to project policies that seek to go beyond a one-dimensional ‘growth agenda’ by addressing also the multifaceted quest for social, economic and environmental sustainability. The underlying shift in discourse, rationality and suggested policy responses in both dimensions may be captured by the concept of ‘transition’ in relation to policies and governance. Originally developed in conjunction with broad political-economic regime change, such as post-authoritarian democratisation, the idea of ‘transition’ has also been applied to the more specific concept of sustainability as ‘sustainability transition’.