One-Bit Covariance Reconstruction with Non-zero Thresholds: Algorithm and Performance Analysis

Covariance matrix reconstruction is a topic of great significance in the field of one-bit signal processing and has numerous practical applications. Despite its importance, the conventional arcsine law with zero threshold is incapable of recovering the diagonal elements of the covariance matrix. To address this limitation, recent studies have proposed the use of non-zero clipping thresholds. However, the relationship between the estimation error and the sampling threshold is not yet known. In this paper, we undertake an analysis of the mean squared error by computing the Fisher information matrix for a given threshold. Our results reveal that the optimal threshold can vary considerably, depending on the variances and correlation coefficients. As a result, it is inappropriate to use a constant threshold to encompass parameters that vary widely. To mitigate this issue, we present a recovery scheme that incorporates time-varying thresholds. Our approach differs from existing methods in that it utilizes the exact values of the threshold, rather than its statistical properties, to enhance the estimation performance. Our simulations, including the direction-of-arrival estimation problem, demonstrate the efficacy of the developed scheme, especially in complex scenarios where the covariance elements are widely separated

Covariance matrix recovery from one-bit data with non-zero quantization thresholds: Algorithm and performance analysis

Covariance matrix recovery is a topic of great significance in the field of one-bit signal processing and has numerous practical applications. Despite its importance, the conventional arcsine law with zero threshold is incapable of recovering the diagonal elements of the covariance matrix. To address this limitation, recent studies have proposed the use of non-zero clipping thresholds. However, the relationship between the estimation error and the sampling threshold is not yet known. In this article, we undertake an analysis of the mean squared error by computing the Fisher information matrix for a given threshold. Our results reveal that the optimal threshold can vary considerably, depending on the variances and correlation coefficients. As a result, it is inappropriate to adopt a constant threshold to encompass parameters that vary widely. To mitigate this issue, we present a recovery scheme that incorporates time-varying thresholds. Our approach differs from existing methods in that it utilizes the exact values of the threshold, rather than its statistical properties, to increase the estimation accuracy. Simulation results, including those of the direction-of-arrival estimation problem, demonstrate the efficacy of the developed scheme, especially in complex scenarios where the covariance elements are widely separated.The work of Yu-Hang Xiao was supported in part by the National Natural Science Foundation of China under Grant 62201359. The work of Lei Huang was supported in part by the National Science Fund for Distinguished Young Scholars under Grant 61925108, and in part by the National Natural Science Foundation of China under Grant U1913221. The work of David Ramírez was supported in part by MCIN/AEI/10.13039/501100011033/FEDER, UE, under Grant PID2021-123182OB-I00 (EPiCENTER), and in part by the Office of Naval Research (ONR) Global under Contract N62909-23-1-2002.Publicad

C-Terminal Binding Protein 2 Is a Novel Tumor Suppressor Targeting the Myc-Irf4 axis in Multiple Myeloma

Multiple myeloma (MM) cells are addicted to MYC and its direct transactivation targets IRF4 for proliferation and survival. MYC and IRF4 are still considered undruggable, as most small-molecule inhibitors suffer from low potency, suboptimal pharmacokinetic properties, and undesirable off-target effects. Indirect inhibition of MYC/IRF4 emerges as a therapeutic vulnerability in MM. Here, we uncovered an unappreciated tumor-suppressive role of C-terminal binding protein 2 (CTBP2) in MM via strong inhibition of the MYC-IRF4 axis. In contrast to epithelial cancers, CTBP2 is frequently downregulated in MM, in association with shortened survival, hyperproliferative features, and adverse clinical outcomes. Restoration of CTBP2 exhibited potent antitumor effects against MM in vitro and in vivo, with marked repression of the MYC-IRF4 network genes. Mechanistically, CTBP2 impeded the transcription of MYC and IRF4 by histone H3 lysine 27 deacetylation (H3K27ac) and indirectly via activation of the MYC repressor IFIT3. In addition, activation of the interferon gene signature by CTBP2 suggested its concomitant immunomodulatory role in MM. Epigenetic studies have revealed the contribution of polycomb-mediated silencing and DNA methylation to CTBP2 inactivation in MM. Notably, inhibitors of Enhance of zeste homolog 2, histone deacetylase, and DNA methyltransferase, currently under evaluation in clinical trials, were effective in restoring CTBP2 expression in MM. Our findings indicated that the loss of CTBP2 plays an essential role in myelomagenesis and deciphers an additional mechanistic link to MYC-IRF4 dysregulation in MM. We envision that the identification of novel critical regulators will facilitate the development of selective and effective approaches for treating this MYC/IRF4-addicted malignancy

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Performance-Appraisal Beliefs of Chinese Employees in Hong Kong and the Pearl River Delta

Working adults from Hong Kong (HK; N=102) and the Pearl River Delta (PRD; N=96) participated in a Chinese-language, 20-item, structured interview. The interview addressed five topics: performance criteria, implementation of the appraisal, factors attributed to performance, methods of feedback, and concerns about the use of performance appraisal (PA) at work. Results indicated that most respondents believe that PA facilitates communication between superiors and subordinates, that effective performance is a function of each individual\u27s internal attributes (which may include aspects external to the workplace), and that feedback should be direct and frank, communicated by someone with authority and power. These results are consistent with the beliefs of people living in societies characterized as high in Confucian dynamism. We discussed implications of the findings for the use of PA in Chinese enterprises in HK and PRD