Design, Application, and Verification of the Novel SEU Tolerant Abacus-Type Layouts

Radiation tolerance improvements for advanced technologies have attracted considerable interests in space application. In this paper, the single event upset (SEU) hardened double interlocked storage cell (DICE) D-type flip-flops (DFFs) with abacus-type time-delay cell are proposed and successfully implemented in our test chips. The layout structures of two kinds of abacus-type time-delay cells are illustrated, and their hardening effectiveness are verified by our simulations and heavy ion irradiations. The systematic heavy ion experimental results show that the applied abacus-type time-delay cells can reduce the SEU cross sections of DICE DFFs significantly, and even the SEU immune is observed for the full “0” data pattern. Besides, an apparent test mode dependency of the abacus-type hardened circuits is also observed. The results indicate that the nanoscale abacus structure may be suitable for space application in harsh radiation environment.

ALL-DIGITAL PHASE LOCKED LOOP (ADPLL) TOPOLOGIES FOR RFID SYSTEM APPLICATION: A REVIEW

An all-digital phase locked loop (ADPLL)-based local oscillator (LO) of RF transceiver application such as radio-frequency identification (RFID) system has gained popularity by accessing the benefits in complementary metal-oxide semiconductor (CMOS) process technology. This paper reviews some state-of-art of the ADPLL structures based on their applications and analyses its major implementation block, which is the digital-controlled oscillator (DCO). The DCO is evaluated based on its CMOS scaling and its performance in ADPLL, such as the power consumption, the chip area, the frequency range, the supply voltage, and the phase noise. Based on the review, the reduction in CMOS scaling decreases the transistor size in ADPLL design which leads to a smaller area and a low power dissipation. The combination of the time-to-digital (TDC) and the digital-to-time converter (DTC) that is used as the phase-frequency detector (PFD) in ADPLL is proposed to reduce the power and phase noise performance due to their high linearity design. The delay cell oscillator is found to consume more power at higher operating frequency, but it has an advantage of having less complexity and consuming less power and area in the circuit compared to the LC tank oscillator. For future work, it is recommended that an ADPLL-based LO of RFID transceiver with lowest voltage supply implementation is chosen and the use of the TDC-less as the PFD is selected due to its small area. While for the DCO, the delay cell will be designed due to its simpler implementation and occupy small area.

The Safe Path at the Fork: Ensuring Replication-Associated DNA Double-Strand Breaks are Repaired by Homologous Recombination

Cells must replicate and segregate their DNA to daughter cells accurately to maintain genome stability and prevent cancer. DNA replication is usually fast and accurate, with intrinsic (proofreading) and extrinsic (mismatch repair) error-correction systems. However, replication forks slow or stop when they encounter DNA lesions, natural pause sites, and difficult-to-replicate sequences, or when cells are treated with DNA polymerase inhibitors or hydroxyurea, which depletes nucleotide pools. These challenges are termed replication stress, to which cells respond by activating DNA damage response signaling pathways that delay cell cycle progression, stimulate repair and replication fork restart, or induce apoptosis. Stressed forks are managed by rescue from adjacent forks, repriming, translesion synthesis, template switching, and fork reversal which produces a single-ended double-strand break (seDSB). Stressed forks also collapse to seDSBs when they encounter single-strand nicks or are cleaved by structure-specific nucleases. Reversed and cleaved forks can be restarted by homologous recombination (HR), but seDSBs pose risks of mis-rejoining by non-homologous end-joining (NHEJ) to other DSBs, causing genome rearrangements. HR requires resection of broken ends to create 3’ single-stranded DNA for RAD51 recombinase loading, and resected ends are refractory to repair by NHEJ. This Mini Review highlights mechanisms that help maintain genome stability by promoting resection of seDSBs and accurate fork restart by HR.

Downregulation of SHCBP1 Inhibits Proliferation, Migration, and Invasion in Human Nasopharyngeal Carcinoma Cells

Background. SHC SH2 domain-binding protein 1 (SHCBP1), one of the members of Src homolog and collagen homolog (Shc) family, has been reported to be overexpressed in several malignant cancers and involved in tumor progression. However, the expression of SHCBP1 in nasopharyngeal carcinoma (NPC) remains unclear, and its clinical significance remains to be further elucidated. Methods. The expression of SHCBP1 mRNA in 35 pair samples of NPC and adjacent normal tissues of NPC was detected by RT-qPCR. The expression level of SHCBP1 protein and mRNA in the selected cells was detected by western blot and RT-qPCR, respectively. The effects of SHCBP1 on NPC in vitro were observed by MTT method, colony formation assay, apoptosis assay, cell cycle assay, wound healing assay, transwell migration assay, and transwell invasion assay. Results. SHCBP1 was highly expressed in clinical tissues and NPC cell lines, and SHCBP1 knockdown significantly inhibited NPC cell proliferation. Overexpression of SHCBP1 promoted NPC cell proliferation, migration, and invasion in NPC cell lines. Silencing SHCBP1 expression can delay cell cycle and inhibit cell apoptosis. Conclusion. Our results suggest that SHCBP1 may promote proliferation and metastasis of NPC cells, which represents that SHCBP1 may act as a new indicator for predicting the prognosis of NPC and a new target for clinical treatment.

Mind the replication gap

Unlike bacteria, mammalian cells need to complete DNA replication before segregating their chromosomes for the maintenance of genome integrity. Thus, cells have evolved efficient pathways to restore stalled and/or collapsed replication forks during S-phase, and when necessary, also to delay cell cycle progression to ensure replication completion. However, strong evidence shows that cells can proceed to mitosis with incompletely replicated DNA when under mild replication stress (RS) conditions. Consequently, the incompletely replicated genomic gaps form, predominantly at common fragile site regions, where the converging fork-like DNA structures accumulate. These branched structures pose a severe threat to the faithful disjunction of chromosomes as they physically interlink the partially duplicated sister chromatids. In this review, we provide an overview discussing how cells respond and deal with the under-replicated DNA structures that escape from the S/G2 surveillance system. We also focus on recent research of a mitotic break-induced replication pathway (also known as mitotic DNA repair synthesis), which has been proposed to operate during prophase in an attempt to finish DNA synthesis at the under-replicated genomic regions. Finally, we discuss recent data on how mild RS may cause chromosome instability and mutations that accelerate cancer genome evolution.

NMDAR Neurotransmission Needed for Persistent Neuronal Firing: Potential Roles in Mental Disorders

The dorsolateral prefrontal cortex (dlPFC) generates the mental representations that are the foundation of abstract thought, and provides top-down regulation of emotion through projections to the medial PFC and cingulate cortices. Physiological recordings from dlPFC Delay cells have shown that the generation of mental representations during working memory relies on NMDAR neurotransmission, with surprisingly little contribution from AMPAR. Systemic administration of low “antidepressant” doses of the NMDAR antagonist, ketamine, erodes these representations and reduces dlPFC Delay cell firing. In contrast to the dlPFC, V1 neuronal firing to visual stimuli depends on AMPAR, with much less contribution from NMDAR. Similarly, neurons in the dlPFC that respond to sensory events (cue cells, response feedback cells) rely on AMPAR, and systemic ketamine increases their firing. Insults to NMDAR transmission, and the impaired ability for dlPFC to generate mental representations, may contribute to cognitive deficits in schizophrenia, e.g., from genetic insults that weaken NMDAR transmission, or from blockade of NMDAR by kynurenic acid. Elevated levels of kynurenic acid in dlPFC may also contribute to cognitive deficits in other disorders with pronounced neuroinflammation (e.g., Alzheimer's disease), or peripheral infections where kynurenine can enter brain (e.g., delirium from sepsis, “brain fog” in COVID19). Much less is known about NMDAR actions in the primate cingulate cortices. However, NMDAR neurotransmission appears to process the affective and visceral responses to pain and other aversive experiences mediated by the cingulate cortices, which may contribute to sustained alterations in mood state. We hypothesize that the very rapid, antidepressant effects of intranasal ketamine may involve the disruption of NMDAR-generated aversive mood states by the anterior and subgenual cingulate cortices, providing a “foot in the door” to allow the subsequent return of top-down regulation by higher PFC areas. Thus, the detrimental vs. therapeutic effects of NMDAR blockade may be circuit dependent.

A multi-octave microwave 6-bit true time delay with low amplitude and delay variation in 65 nm CMOS

In this paper, we describe the design, layout, and performance of a 6-bit TTD (true time delay) chip operating over the entire band of 2–18 GHz. The 1.15 mm2 chip is implemented using TSMC foundry 65 nm technology. The least significant bit is 1 ps. The design is based on the concept of all-pass network with some modifications intended to reduce the number of unit cells. Thus, the first three bits are implemented in a single delay cell. A peaking buffer amplifier between bit 4 and bit 5 is used for impedance matching and partial compensation of the insertion loss slope. The rms delay error of the TTD is <1 ps over most of the frequency band and insertion loss is between 2.5 and 6.3 dB for all 64 states.