An in-band full-duplex radio receiver with a passive vector modulator downmixer for self-interference cancellation

In-band full-duplex (FD) wireless, i.e., simultaneous transmission and reception at the same frequency, introduces strong self-interference (SI) that masks the signal to be received. This paper proposes a receiver in which a copy of the transmit signal is fed through a switched-resistor vector modulator (VM)that provides simultaneous downmixing, phase shift, and amplitude scaling and subtracts it in the analog baseband for up to 27 dB SI-cancellation. Cancelling before active baseband amplification avoids self-blocking, and highly linear mixers keep SIinduced distortion low, for a receiver SI-to-noise-and-distortionratio (SINDR) of up to 71.5 dB in 16.25 MHz BW. When combined with a two-port antenna with only 20 dB isolation, the low RX distortion theoretically allows sufficient digital cancellation for over 90 dB link budget, sufficient for short-range, low-power FD links

A self-interference-cancelling receiver for in-band full-duplex wireless with low distortion under cancellation of strong TX leakage

In-band full-duplex (FD) wireless communication, i.e. simultaneous transmission and reception at the same frequency, in the same channel, promises up to 2x spectral efficiency, along with advantages in higher network layers [1]. the main challenge is dealing with strong in-band leakage from the transmitter to the receiver (i.e. self-interference (SI)), as TX powers are typically >100dB stronger than the weakest signal to be received, necessitating TX-RX isolation and SI cancellation. Performing this SI-cancellation solely in the digital domain, if at all possible, would require extremely clean (low-EVM) transmission and a huge dynamic range in the RX and ADC, which is currently not feasible [2]. Cancelling SI entirely in analog is not feasible either, since the SI contains delayed TX components reflected by the environment. Cancelling these requires impractically large amounts of tunable analog delay. Hence, FD-solutions proposed thus far combine SI-rejection at RF, analog BB, digital BB and cross-domain

Autophagy-mediated degradation of nuclear envelope proteins during oncogene-induced senescence

Here, we report that nuclear envelope proteins are subjected to autophagic proteolysis in human cells undergoing oncogene-induced senescence. This degradation occurs in parallel with autophagy and lysosomal activity induction that accompanies the establishment of the senescence respons

Real-time observation of DNA looping dynamics of Type IIE restriction enzymes NaeI and NarI

Many restriction enzymes require binding of two copies of a recognition sequence for DNA cleavage, thereby introducing a loop in the DNA. We investigated looping dynamics of Type IIE restriction enzymes NaeI and NarI by tracking the Brownian motion of single tethered DNA molecules. DNA containing two endonuclease recognition sites spaced a few 100 bp apart connect small polystyrene beads to a glass surface. The position of a bead is tracked through video microscopy. Protein-mediated looping and unlooping is then observed as a sudden specific change in Brownian motion of the bead. With this method we are able to directly follow DNA looping kinetics of single protein–DNA complexes to obtain loop stability and loop formation times. We show that, in the absence of divalent cations, NaeI induces DNA loops of specific size. In contrast, under these conditions NarI mainly creates non-specific loops, resulting in effective DNA compaction for higher enzyme concentrations. Addition of Ca(2+) increases the NaeI-DNA loop lifetime by two orders of magnitude and stimulates specific binding by NarI. Finally, for both enzymes we observe exponentially distributed loop formation times, indicating that looping is dominated by (re)binding the second recognition site

Negative regulation of urokinase receptor activity by a GPI-specific phospholipase C in breast cancer cells.

The urokinase receptor (uPAR) is a glycosylphosphatidylinositol (GPI)-anchored protein that promotes tissue remodeling, tumor cell adhesion, migration and invasion. uPAR mediates degradation of the extracellular matrix through protease recruitment and enhances cell adhesion, migration and signaling through vitronectin binding and interactions with integrins. Full-length uPAR is released from the cell surface, but the mechanism and significance of uPAR shedding remain obscure. Here we identify transmembrane glycerophosphodiesterase GDE3 as a GPI-specific phospholipase C that cleaves and releases uPAR with consequent loss of function, whereas its homologue GDE2 fails to attack uPAR. GDE3 overexpression depletes uPAR from distinct basolateral membrane domains in breast cancer cells, resulting in a less transformed phenotype, it slows tumor growth in a xenograft model and correlates with prolonged survival in patients. Our results establish GDE3 as a negative regulator of the uPAR signaling network and, furthermore, highlight GPI-anchor hydrolysis as a cell-intrinsic mechanism to alter cell behavior

Sustained CHK2 activity, but not ATM activity, is critical to maintain a G1 arrest after DNA damage in untransformed cells

BACKGROUND: The G1 checkpoint is a critical regulator of genomic stability in untransformed cells, preventing cell cycle progression after DNA damage. DNA double-strand breaks (DSBs) recruit and activate ATM, a kinase which in turn activates the CHK2 kinase to establish G1 arrest. While the onset of G1 arrest is well understood, the specific role that ATM and CHK2 play in regulating G1 checkpoint maintenance remains poorly characterized. RESULTS: Here we examine the impact of ATM and CHK2 activities on G1 checkpoint maintenance in untransformed cells after DNA damage caused by DSBs. We show that ATM becomes dispensable for G1 checkpoint maintenance as early as 1h after DSB induction. In contrast, CHK2 kinase activity is necessary to maintain the G1 arrest, independently of ATM, ATR, and DNA-PKcs, implying that the G1 arrest is maintained in a lesion-independent manner. Sustained CHK2 activity is achieved through auto-activation and its acute inhibition enables cells to abrogate the G1-checkpoint and enter into S-phase. Accordingly, we show that CHK2 activity is lost in cells that recover from the G1 arrest, pointing to the involvement of a phosphatase with fast turnover. CONCLUSION: Our data indicate that G1 checkpoint maintenance relies on CHK2 and that its negative regulation is crucial for G1 checkpoint recovery after DSB induction.This research was funded by grants from MCIU/AEI/FEDER, UE (SAF2015-67562-R and RTI2018-097497-B-100) and Basque Government, Department of Education (IT1257-19) to A.M.Z., and Cancer Genomics Center Gravity Program (CGC.nl), Oncode Institute, Dutch Cancer Society (NKI 2014-6787) grants to R.H.M. I.G.-S. was supported with a postdoctoral fellowship from the Basque Country Government (Spain). J.V.-R. was supported by a postdoctoral fellowship from the University of the Basque Country (UPV/EHU)

Doxorubicin-induced DNA Damage Causes Extensive Ubiquitination of Ribosomal Proteins Associated with a Decrease in Protein Translation

Protein posttranslational modifications (PTMs) play a central role in the DNA damage response. In particular, protein phosphorylation and ubiquitination have been shown to be essential in the signaling cascade that coordinates break repair with cell cycle progression. Here, we performed whole-cell quantitative proteomics to identify global changes in protein ubiquitination that are induced by DNA double-strand breaks. In total, we quantified more than 9,400 ubiquitin sites and found that the relative abundance of similar to 10% of these sites was altered in response to DNA double-strand breaks. Interestingly, a large proportion of ribosomal proteins, including those from the 40S as well as the 60S subunit, were ubiquitinated in response to DNA damage. In parallel, we discovered that DNA damage leads to the inhibition of ribosome function. Taken together, these data uncover the ribosome as a major target of the DNA damage response.This work is funded by a TOP-GO grant from the Netherlands Organization for Scientific Research (NWO ZonMW 912100651 to R.H.M., S.M., and V.A.H.). I.G.S. was supported with a postdoctoral fellowship from the Basque Country Government (Spain). We thank Christian Frese and Teck Yew Low for fruitful discussions. We also thank Teck Yew Low for submitting the raw files and annotated spectra to PRIDE. We thank Fabricio Loayza-Puch for his technical help with the sucrose gradients

Accelerated development of cerebral small vessel disease in young stroke patients.

OBJECTIVE: To study the long-term prevalence of small vessel disease after young stroke and to compare this to healthy controls. METHODS: This prospective cohort study comprises 337 patients with an ischemic stroke or TIA, aged 18-50 years, without a history of TIA or stroke. In addition, 90 age- and sex-matched controls were included. At follow-up, lacunes, microbleeds, and white matter hyperintensity (WMH) volume were assessed using MRI. To investigate the relation between risk factors and small vessel disease, logistic and linear regression were used. RESULTS: After mean follow-up of 9.9 (SD 8.1) years, 337 patients were included (227 with an ischemic stroke and 110 with a TIA). Mean age of patients was 49.8 years (SD 10.3) and 45.4% were men; for controls, mean age was 49.4 years (SD 11.9) and 45.6% were men. Compared with controls, patients more often had at least 1 lacune (24.0% vs 4.5%, p < 0.0001). In addition, they had a higher WMH volume (median 1.5 mL [interquartile range (IQR) 0.5-3.7] vs 0.4 mL [IQR 0.0-1.0], p < 0.001). Compared with controls, patients had the same volume WMHs on average 10-20 years earlier. In the patient group, age at stroke (β = 0.03, 95% confidence interval [CI] 0.02-0.04) hypertension (β = 0.22, 95% CI 0.04-0.39), and smoking (β = 0.18, 95% CI 0.01-0.34) at baseline were associated with WMH volume. CONCLUSIONS: Patients with a young stroke have a higher burden of small vessel disease than controls adjusted for confounders. Cerebral aging seems accelerated by 10-20 years in these patients, which may suggest an increased vulnerability to vascular risk factors.This is the final version of the article. It first appeared from Wolters Kluwer via https://doi.org/10.​1212/​WNL.​0000000000003123

Six weeks Use of a Wearable Soft-robotic Glove During ADL:Preliminary Results of Ongoing Clinical Study

In this ongoing study, an assistive wearable soft-robotic glove, named Carbonhand, is tested at home for 6 weeks by subjects with decreased handgrip strength to receive a first insight in the therapeutic effect of using this assistive grip-supporting glove during ADLs. Preliminary results of the first 13 participants showed that participants appreciated use of the glove to assist them with daily life activities. Even more, grip strength without glove improved and functional performance showed increases as well. These preliminary findings hold promise for observing a clinical effect of using the soft-robotic glove as assistance in ADLs upon completion of data collection