Synchronization of pulse-coupled oscillators (PCOs) has gained significant attention recently due to their increased applications in sensor networks and wireless communications. Given the distributed ...and unattended nature of wireless sensor networks, it is imperative to enhance the resilience of PCO synchronization against malicious attacks. However, most existing results on attack-resilient pulse-based synchronization are obtained under assumptions of all-to-all coupling topologies or restricted initial phase distributions. In this paper, we propose a new pulse-based synchronization mechanism to improve the attack resilience of PCO synchronization that is applicable to non-all-to-all networks. Under the proposed synchronization mechanism, we prove that perfect synchronization of legitimate oscillators can be guaranteed in the presence of multiple Byzantine attackers who can emit attack pulses arbitrarily without any constraint except that practical bit rate constraint renders the number of pulses from an attacker to be finite. The new mechanism can guarantee synchronization even when the initial phases of all legitimate oscillators are arbitrarily distributed in the entire oscillation period, which is in distinct difference from most existing attack-resilient synchronization approaches (including the seminal paper from Lamport and Melliar-Smith <xref ref-type="bibr" rid="ref1">1 ) that require a priori (almost) synchronization among legitimate oscillators. Numerical simulation results are given to confirm the theoretical results.
Abstract
With great interest, we have read the recent article “Age at menarche, age at natural menopause, and risk of rheumatoid arthritis — a Mendelian randomization study” by Zhu et al. While we ...have a great appreciation for the work conducted by the authors, there are some methodological issues that need to be reconsidered. First, the gender description of the sample for age at first birth in this study is wrong according to the original genome-wide association study. Second, the study exploited sex-specific SNPs for age at menarche (AAM) and age at natural menopause (ANM) but sex-combined effects of the SNPs on rheumatoid arthritis (RA) that possibly lead no evidence for the causation of AAM and ANM on RA. We suggested the author add the possible biases due to the issue in the limitations. With problems mentioned above, we recommend solutions to make this article more perfect.
Conflicting reconstructions of Holocene variability of the East Asian summer monsoon (EASM) from speleothem versus other types of proxy records have yielded widely divergent estimates of its phase ...relationship with the Indian summer monsoon (ISM) and Northern Hemisphere summer insolation (NHSI). This apparent discrepancy has been partly attributed to the uncertainties in the climatic representation of Chinese speleothem oxygen isotope (δ18O) records. Here we present a composite speleothem δ18O record of the last ∼14 kyr from Shennong Cave in southeastern China and model-simulated data of rainfall and meteoric δ18O over eastern China. Our synthesis of the proxy-model data suggests that the spatial patterns in both speleothem δ18O and paleo-rainfall over eastern China during the Holocene are diverse at orbital and multi-millennial scales. Our findings imply that: 1) speleothem δ18O in the EASM regime is largely controlled by the large-scale circulation and concomitant latitudinal shifts of the monsoon rain belt; notwithstanding the heterogeneous spatiotemporal pattern of Holocene rainfall as inferred from various proxy records, a coherent orbital-scale speleothem δ18O variability across most Asian monsoon regions (except southeastern China) indeed stems from the NHSI-forced changes in overall monsoon intensity; overall monsoon intensity is not equivalent to monsoon rainfall amount but a manifestation of the large-scale atmospheric circulation; 2) divergent phase relationships with NHSI between speleothem δ18O and other proxy records are consistent with—rather than contradictory to—the NHSI forcing mechanism. Speleothem δ18O and rainfall records reflect two different aspects of the monsoon dynamics. These results may thus, largely help to reconcile the divergent views of the Holocene Asian monsoon variability.
•Holocene speleothem δ18O and rainfall show heterogeneous pattern in eastern China.•East Asian speleothem δ18O reflects large-scale circulation and monsoon rain belt shift.•Divergent phases between speleothem and other proxy records are not contradictory.
Synchronization of bio-inspired pulse-coupled oscillators is receiving increased attention due to its wide applications in sensor networks and wireless communications. However, most existing results ...are obtained in the absence of malicious attacks. Given the distributed and unattended nature of wireless sensor networks, it is imperative to enhance the resilience of pulse based synchronization against malicious attacks. To achieve this goal, we propose a new pulse based interaction mechanism to improve the resilience of pulse based synchronization. We rigorously characterize the condition for mounting stealthy attacks under the proposed pulse based interaction mechanism and prove analytically that synchronization of legitimate oscillators can be achieved in the presence of multiple stealthy attackers even when the initial phases are unrestricted, i.e., randomly distributed in the entire oscillation period. This is in distinct difference from most existing attack-resilient synchronization algorithms (including the seminal paper from L. Lamport and P. M. Melliar-Smith, "Synchronizing Clocks in the Presence of Faults," J. ACM, vol. 32, no. 1, pp. 52-78, 1985), which require a priori (almost) synchronization among legitimate nodes. Numerical simulations are given to confirm the theoretical results.
Increasing evidence shows that systemic inflammation is an embedded mechanism of proliferative diabetic retinopathy (PDR). However, the specific systemic inflammatory factors involved in this process ...remained obscure. The study aimed to identify the upstream and downstream systemic regulators of PDR by using Mendelian randomization (MR) analyses.
We performed a bidirectional two-sample MR analysis implementing the results from genome-wide association studies for 41 serum cytokines from 8,293 Finnish individuals, and PDR from FinnGen consortium (2,025 cases vs. 284,826 controls) and eight cohorts of European ancestry (398 cases vs. 2,848 controls), respectively. The inverse-variance-weighted method was adopted as the main MR method, and four additional MR methods (MR-Egger, weighted-median, MR-pleiotropy residual sum and outlier (MR-PRESSO), and MR-Steiger filtering methods) were used for the sensitivity analyses. Results from FinnGen and eight cohorts were pooled into a meta-analysis.
Our results showed that genetically predicted higher stem cell growth factor-β (SCGFb) and interleukin-8 were positively associated with an elevated risk of PDR, with a combined effect of one standard deviation (SD) increase in SCGFb and interleukin-8 causing 11.8% 95% confidence interval (CI): 0.6%, 24.2%) and 21.4% 95% CI: 3.8%, 41.9%) higher risk of PDR, respectively. In contrast, genetically predisposition to PDR showed a positive association with the increased levels of growth-regulated oncogene-α (GROa), stromal cell-derived factor-1 alpha (SDF1a), monocyte chemotactic protein-3 (MCP3), granulocyte colony-stimulating factor (GCSF), interleukin-12p70, and interleukin-2 receptor subunit alpha (IL-2ra).
Our MR study identified two upstream regulators and six downstream effectors of PDR, providing opportunities for new therapeutic exploitation of PDR onset. Nonetheless, these nominal associations of systemic inflammatory regulators and PDR require validation in larger cohorts.
Background Multiple myeloma (MM) is a severely debilitating and fatal B-cell neoplastic disease. The discovery of disease-associated proteins with causal genetic evidence offers a chance to uncover ...novel therapeutic targets. Methods First, we comprehensively investigated the causal association between 2994 proteins and MM through two-sample mendelian randomization (MR) analysis using summary-level data from public genome-wide association studies of plasma proteome (N = 3301 healthy individuals) and MM (598 cases and 180,756 controls). Sensitivity analyses were performed for these identified causal proteins. Furthermore, we pursued the exploration of enriched biological pathways, prioritized the therapeutic proteins, and evaluated their druggability using the KEGG pathway analysis, MR-Bayesian model averaging analysis, and cross-reference with current databases, respectively. Results We identified 13 proteins causally associated with MM risk (false discovery rate corrected P < 0.05). Six proteins were positively associated with the risk of MM, including nicotinamide phosphoribosyl transferase (NAMPT; OR 95% CI: 1.35 1.18, 1.55), tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE1; 1.14 1.06, 1.22), neutrophil cytosol factor 2 (NCF2; 1.27 1.12, 1.44), carbonyl reductase 1, cAMP-specific 3',5'-cyclic phosphodiesterase 4D (PDE4D), platelet-activating factor acetylhydrolase IB subunit beta (PAFAH1B2). Seven proteins were inversely associated with MM, which referred to suppressor of cytokine signaling 3 (SOCS3; 0.90 0.86, 0.94), Fc-gamma receptor III-B (FCGR3B; 0.75 0.65,0.86), glypican-1 (GPC1; 0.69 0.58,0.83), follistatin-related protein 1, protein tyrosine phosphatase non-receptor type 4 (PTPN4), granzyme B, complement C1q subcomponent subunit C (C1QC). Three of the causal proteins, SOCS3, FCGR3B, and NCF2, were enriched in the osteoclast differentiation pathway in KEGG enrichment analyses while GPC1 (marginal inclusion probability (MIP):0.993; model averaged causal effects (MACE): - 0.349), NAMPT (MIP:0.433; MACE: - 0.113), and NCF2 (MIP:0.324; MACE:0.066) ranked among the top three MM-associated proteins according to MR-BMA analyses. Furthermore, therapeutics targeting four proteins are currently under evaluation, five are druggable and four are future breakthrough points. Conclusions Our analysis revealed a set of 13 novel proteins, including six risk and seven protective proteins, causally linked to MM risk. The discovery of these MM-associated proteins opens up the possibility for identifying novel therapeutic targets, further advancing the integration of genome and proteome data for drug development. Keywords: Plasma proteome, Multiple myeloma, Drug target, Bayesian model, Mendelian randomization, Enrichment pathway analysis
•Response of vegetation to drought varies greatly in different climatic regions.•The effect of drought on vegetation in humid areas is lower than that in dry area.•Water balance plays a key role in ...affecting the response of vegetation to drought.•The sensitivity of different vegetation to drought is quite different.
Drought is the most widespread event under climate change and is projected to lead to high uncertainties in quantifying the terrestrial carbon exchange. However, considering the complexity of drought quantification and the differences in the physiological responses to drought among different vegetation types, the potential mechanisms of vegetation in response to drought across different climate regions and their responses to drought at varying time scales remain unclear globally. Here, we analyzed the response of vegetation activity to drought at different time scales and determined the time scale dominating the drought-induced vegetation variations, then explored its potential driving factors (temperature, precipitation, potential evapotranspiration, and water balance) under different climatic conditions and vegetation types from 2000 to 2015 using the Standardized Precipitation Evapotranspiration Index (SPEI) and Net Primary Productivity (NPP). Our results indicated that the NPP-SPEI correlation was stronger under arid and semi-arid conditions compared to that in humid and sub-humid zones globally. Vegetation mainly responded to the drought from short to medium time scales and the shortest response time scale was observed for deciduous needle-leaf forests and closed shrublands, which mainly located in semi-arid regions of southeastern Australia, central Africa, and southern Russia. Moreover, grassland and cropland ecosystems were found to be also highly vulnerable to drought across the globe. Analysis of the effects of various meteorological factors on NPP-SPEI correlation and drought timescales showed that water balance was the most predominant factor affecting the response of vegetation to drought. In particular, the increase in water balance significantly reduced the response intensity of vegetation to drought and prolonged the response timescales. Analysis of the effects of various meteorological factors on NPP-SPEI correlation and drought time-scales showed that water balance was the most predominant factor affecting the response of vegetation to drought. In particular, the increase in water balance significantly reduces the response intensity of vegetation to drought and prolongs the response time-scales. Therefore, the identification of the dominant timescales at which drought mostly impact land biomes is projected to assist assessing the stability of terrestrial ecosystem and thus support drought mitigation to reduce land degradation.
Abstract
In this study we presented a composite standard chronology, spanning 1635–2018 to reconstruct May–July moisture variation in north central China. Our reconstruction revealed four severe dry ...epochs and five pronounced wet epochs. Additionally, spatial correlation analysis of our reconstruction with the actual self-calibrating Palmer drought severity index showed that our reconstruction was representative of large-scale May–July moisture changes. Both the severe dry and pronounced wet epochs showed one-to-one correspondence with other reconstructions nearby during their common periods, which demonstrated the reliability of our reconstruction backwards in time. Spectral analysis showed that significant spectral peaks were found at 2.1–3.8 years, which fell within the overall bandwidth of the El Niño-Southern Oscillations (ENSO). The spatial correlation patterns between our reconstruction and sea surface temperature (SST) in the equatorial eastern Pacific further confirmed the link between regional moisture and ENSO, with warm-phase ENSO resulting in low moisture and vice-versa. However, this link was time-dependent during the past four centuries, and was modulated by different phases of SST in the tropical Indian Ocean. Additionally, significant peaks at 24.9–46.5 years and spatial correlation patterns indicated that the Pacific Decadal Oscillation and the North Atlantic Oscillation may be the possible forcing factors of regional moisture at lower frequencies.
Dyslipidemia has long been implicated in elevating mortality risk; yet, the precise associations between lipid traits and mortality remained undisclosed. Our study aimed to explore the causal effects ...of lipid traits on both all-cause and cause-specific mortality. One-sample Mendelian randomization (MR) with linear and nonlinear assumptions was conducted in a cohort of 407,951 European participants from the UK Biobank. Six lipid traits, consisting of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a), were included to investigate the causal associations with mortality. Two-sample MR was performed to replicate the association between each lipid trait and all-cause mortality. Univariable MR results showed that genetically predicted higher ApoA1 was significantly associated with a decreased all-cause mortality risk (HR95% CI:0.93 0.89–0.97, P value = 0.001), which was validated by the two-sample MR analysis. Higher lipoprotein(a) was associated with an increased risk of all-cause mortality (1.03 1.01–1.04, P value = 0.002). Multivariable MR confirmed the direct causal effects of ApoA1 and lipoprotein(a) on all-cause mortality. Meanwhile, nonlinear MR found no evidence for nonlinearity between lipids and all-cause mortality. Our examination into cause-specific mortality revealed a suggestive inverse association between ApoA1 and cancer mortality, a significant positive association between lipoprotein(a) and cardiovascular disease mortality, and a suggestive positive association between lipoprotein(a) and digestive disease mortality. High LDL-C was associated with an increased risk of cardiovascular disease mortality but a decreased risk of neurodegenerative disease mortality. The findings suggest that implementing interventions to raise ApoA1 and decrease lipoprotein(a) levels may improve overall health outcomes and mitigate cancer and digestive disease mortality.
The pattern of changes in Holocene moisture conditions in the southern Tibetan Plateau (TP) and the associated driving mechanism are still controversial. Here, we present the results of an analysis ...of an aeolian sedimentary sequence from the Yarlung Zangbo River valley in the southern TP, which potentially provides a record of changes in moisture conditions during the Holocene, and hence changes in the atmospheric circulation process. Optically stimulated luminescence dating with the single-aliquot regeneration protocol was used to establish the chronology for the sequence, and geochemical and granulometric measurements were used to reconstruct the Holocene moisture history. The results indicate that moisture conditions were strongly influenced by the early Holocene maximum in summer insolation (30°N) and hence by the Indian summer monsoon (ISM), under which the weathering intensity was relatively high. However, at ∼7.6 ka the climate abruptly became drier, probably due to the weakening of the ISM. Subsequently, with the further decrease in summer insolation and increase in winter insolation, the variations in ISM-related moisture delivery to the southern TP were regulated by the enhanced winter mid-latitude Westerlies (MLW), resulting in increasing weathering intensity. Thus, the Holocene evolution of moisture conditions in the southern TP was mainly controlled by changes in the relative intensities of the ISM and the winter MLW, which depended on the variations of summer and winter insolation at 30°N. Overall, our results provide an improved understanding of the driving mechanism of climate change in the southern TP during the Holocene.
•Holocene moisture variations in the southern Tibetan Plateau were reconstructed.•A wetter early and late Holocene and a drier middle Holocene were found.•The moisture was influenced by the Indian summer monsoon and the winter mid-latitude Westerlies.•Moisture evolution depended on the variations of summer and winter insolation at 30°N.
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