Cmos Programmable Time Control Circuit Design For Phased Array Uwb Ground Penetrating Radar Antenna Beamforming

Phased array radar systems employ multiple antennas to create a radar beam that can be steered electronically. By manipulating the relative phase values of feeding signals among different antennas, the effective radiation pattern of the array can be synthesized to enhance the main lobe in a desired direction while suppressing the undesired side lobes in other directions. Hence the radar scanning angles can be electronically controlled without employing the bulky mechanical gimbal structure, which can significantly reduce radar system size, weight and power consumption. In recent years, phased array technologies have received great attentions and are explored in developing many new applications, such as smart communication systems, military radars, vehicular radar, etc. Most of these systems are narrow band systems, where the phase delays are realized with narrow band phase shifter circuits. For the impulse ground penetrating radar however, its operating frequency spans an ultrawide bandwidth. Therefore the traditional phase shifters are not applicable due to their narrow band nature. To resolve the issue, in this study, a true time delay approach is explored which can precisely control time delays for the feeding pulse signals among different antennas in the array. In the design, an on chip programmable delay generator is being developed using Global Foundry 0.18 µm 7 HV high voltage CMOS process. The time delay control is realized by designing a programmable phase locked loop (PLL) circuit which can generate true time delays ranging from 100 ps (picoseconds) to 500 ps with the step size of 25 ps. The PLL oscillator\u27s frequency is programmable from 100MHz to 500MHz through two reconfigurable frequency dividers in the feedback loop. As a result, the antenna beam angle can be synthesized to change from 9.59° to 56.4° with a step of 2.75°, and the 3dB beamwidth is 10°. The power consumption of the time delay circuit is very low, where the supply voltage is 1.8V and the average current is as low as 472uA

Structural basis for plexin activation and regulation

Class A plexins (PlxnAs) act as semaphorin receptors and control diverse aspects of nervous system development and plasticity, ranging from axon guidance and neuron migration to synaptic organization. PlxnA signaling requires cytoplasmic domain dimerization but extracellular regulation and activation mechanisms remain unclear. Here we present crystal structures of PlxnA (PlxnA1, PlxnA2 and PlxnA4) full ectodomains. Domains 1-9 form a ring-like conformation from which the C-terminal domain 10 points away. All our PlxnA ectodomain structures show autoinhibitory, intermolecular “head-to-stalk” (domain 1 to domain 4-5) interactions, which are confirmed by biophysical assays, live cell fluorescence microscopy, and cell-based and neuronal growth cone collapse assays. This work reveals a two-fold role of the PlxnA ectodomains: imposing a pre-signaling autoinhibitory separation for the cytoplasmic domains via intermolecular head-to-stalk interactions, and supporting dimerization-based PlxnA activation upon ligand binding. More generally, our data identify a novel molecular mechanism for preventing premature activation of axon guidance receptors

Developmental and Activity-Dependent miRNA Expression Profiling in Primary Hippocampal Neuron Cultures

MicroRNAs (miRNAs) are evolutionarily conserved non-coding RNAs of similar to 22 nucleotides that regulate gene expression at the level of translation and play vital roles in hippocampal neuron development, function and plasticity. Here, we performed a systematic and in-depth analysis of miRNA expression profiles in cultured hippocampal neurons during development and after induction of neuronal activity. MiRNA profiling of primary hippocampal cultures was carried out using locked nucleic-acid-based miRNA arrays. The expression of 264 different miRNAs was tested in young neurons, at various developmental stages (stage 2-4) and in mature fully differentiated neurons (stage 5) following the induction of neuronal activity using chemical stimulation protocols. We identified 210 miRNAs in mature hippocampal neurons; the expression of most neuronal miRNAs is low at early stages of development and steadily increases during neuronal differentiation. We found a specific subset of 14 miRNAs with reduced expression at stage 3 and showed that sustained expression of these miRNAs stimulates axonal outgrowth. Expression profiling following induction of neuronal activity demonstrates that 51 miRNAs, including miR-134, miR-146, miR-181, miR-185, miR-191 and miR-200a show altered patterns of expression after NMDA receptor-dependent plasticity, and 31 miRNAs, including miR-107, miR-134, miR-470 and miR-546 were upregulated by homeostatic plasticity protocols. Our results indicate that specific miRNA expression profiles correlate with changes in neuronal development and neuronal activity. Identification and characterization of miRNA targets may further elucidate translational control mechanisms involved in hippocampal development, differentiation and activity-depended processes

Antagonizing increased miR-135a levels at the chronic stage of experimental TLE reduces spontaneous recurrent seizures

Mesial Temporal Lobe Epilepsy (mTLE) is a chronic neurological disease characterized by recurrent seizures. The anti-epileptic drugs currently available to treat mTLE are ineffective in one-third of patients and lack disease-modifying effects. MicroRNAs (miRNAs), a class of small non-coding RNAs which control gene expression at the post-transcriptional level, play a key role in the pathogenesis of mTLE and other epilepsies. Although manipulation of miRNAs at acute stages has been reported to reduce subsequent spontaneous seizures, it is uncertain whether targeting miRNAs at chronic stages of mTLE can also reduce seizures. Furthermore, the functional role and downstream targets of most epilepsy-associated miRNAs remain poorly understood. Here, we show that miR-135a is selectively upregulated within neurons in epileptic brain and report that targeting miR-135a in vivo using antagomirs after onset of spontaneous recurrent seizures can reduce seizure activity at the chronic stage of experimental mTLE in male mice. Further, by using an unbiased approach combining immunoprecipitation and RNA sequencing, we identify several novel neuronal targets of miR-135a, including Mef2a. Mef2 proteins are key regulators of excitatory synapse density. Mef2a and miR-135a show reciprocal expression regulation in human (of both sexes) and experimental TLE, and miR-135a regulates dendritic spine number and type through Mef2. Together, our data show that miR-135a is target for reducing seizure activity in chronic epilepsy, and that deregulation of miR-135a in epilepsy may alter Mef2a expression and thereby affect synaptic function and plasticity.Significance statementmiRNAs are post-transcriptional regulators of gene expression with roles in the pathogenesis of epilepsy. However, the precise mechanism-of-action and therapeutic potential of most epilepsy-associated miRNAs remain poorly understood. Our study reveals dramatic upregulation of the key neuronal miRNA miR-135a in both experimental and human mTLE. Silencing miR-135a in experimental TLE reduces seizure activity at the spontaneous recurrent seizure stage. These data support the exciting possibility that miRNAs can be targeted to combat seizures after spontaneous seizure activity has been established. Further, by using unbiased approaches novel neuronal targets of miR-135a, including members of the Mef2 protein family, are identified that begin to explain how deregulation of miR-135a may contribute to epilepsy