Trace fossils are structures left in a substrate as the result of the activities of living organisms. The producer of the spindle-shaped trace fossil Rosselia incorporates fine-grained organic rich ...material into concentric layers surrounding the central shaft. Because Rosselia is common in stressed shallow marine environments where the preservation potential of organic material is generally poor, these trace fossils may act as natural archives, recording changes in the provenance of organic material. Carbon isotope values of organic carbon preserved in laminae of the studied Rosselia typically lie around - 26‰, suggesting a primary terrestrial source. However, increased levels of S and Ca detected from XRF scanning of the laminae indicate that at least some marine material is incorporated. Examination of a diagenetically altered specimen also demonstrates that both elemental composition and δ
C values can be substantially altered diagenesis. Nevertheless, the long stratigraphic range of Rosselia, from the Cambrian to the Present, and its ubiquitous occurrence in stressed shallow-marine settings make it a potentially powerful tool to reconstruct variations in the input of organic material in settings otherwise devoid of fine-grained organic matter.
A 60 GHz wide locking range Miller divider is presented in this letter. To enhance the locking range of divider and save power consumption, we proposed a Miller divider based on weak inversion mixer. ...The proposed Miller divider is implemented in 65 nm CMOS and exhibits 57% locking range from 35.7 to 64.2 GHz at an input power of 0 dBm while consuming 1.6-mW dc power at 0.4 V supply. Compared to the previously reported CMOS millimeter wave frequency dividers, the proposed divider achieves the widest fractional bandwidth without any frequency tuning mechanism.
The aggressive nature and poor prognosis of lung cancer led us to explore the mechanisms driving disease progression. Utilizing our invasive cell‐based model, we identified methylthioadenosine ...phosphorylase (MTAP) and confirmed its suppressive effects on tumorigenesis and metastasis. Patients with low MTAP expression display worse overall and progression‐free survival. Mechanistically, accumulation of methylthioadenosine substrate in MTAP‐deficient cells reduce the level of protein arginine methyltransferase 5 (PRMT5)‐mediated symmetric dimethylarginine (sDMA) modification on proteins. We identify vimentin as a dimethyl‐protein whose dimethylation levels drop in response to MTAP deficiency. The sDMA modification on vimentin reduces its protein abundance but trivially affects its filamentous structure. In MTAP‐deficient cells, lower sDMA modification prevents ubiquitination‐mediated vimentin degradation, thereby stabilizing vimentin and contributing to cell invasion. MTAP and PRMT5 negatively correlate with vimentin in lung cancer samples. Taken together, we propose a mechanism for metastasis involving vimentin post‐translational regulation.
Synopsis
Repression of MTAP‐dependent symmetric dimethylation mediated by PRMT5 increases vimentin protein stability and leads to invasion and metastasis in MTAP‐deficient lung cancer.
MTAP loss promotes lung cancer metastasis.
MTA accumulation in MTAP‐deficient cancer cells inhibits PRMT5‐mediated symmetric dimethylation on arginine residues of vimentin.
Vimentin is destabilized by PRMT5‐mediated symmetric dimethylation.
Reduced dimethylation and stabilization of vimentin in MTAP‐deficient cancer cells contributes to invasion and metastasis.
Repression of MTAP‐dependent symmetric dimethylation mediated by PRMT5 increases vimentin protein stability and leads to invasion and metastasis in MTAP‐deficient lung cancer.
Resistive random access memory (ReRAM) is often considered as a strong candidate for storing the weights in non-von Neumann neuromorphic computing systems. This paper studies how nonideal memory ...characteristics, which include programing error, read fluctuation, and retention, affect the inference accuracy of the analog ReRAM neural networks by incorporating memory characteristics extracted from 1-Mb ReRAM into a simulated inference-only neural network. This paper also shows that the different layer in the network can tolerate different amount of such imperfects. We learned four key points: 1) the conductance range of memory with less relative fluctuation is preferred for designing the weight-conductance mapping; 2) the control of programing error is essential for high inference accuracy; 3) retention-induced conductance drift can be fatal to the neuromorphic system. A compensation scheme is proposed in this paper which can effectively recover the inference accuracy; and 4) for multilayer networks, avoiding weight errors in the front layers can help to maintain the inference accuracy by reducing calculation error which may otherwise accumulate and pass down the networks. The concepts and approaches of this paper can also be applied to evaluate other types of nonvolatile memories for artificial neural networks.
Cellular senescence is a state of cell cycle arrest characterized by a distinct morphology, gene expression pattern, and secretory phenotype. It can be triggered by multiple mechanisms, including ...those involved in telomere shortening, the accumulation of DNA damage, epigenetic pathways, and the senescence-associated secretory phenotype (SASP), and so on. In current cancer therapy, cellular senescence has emerged as a potent tumor suppression mechanism that restrains proliferation in cells at risk for malignant transformation. Therefore, compounds that stimulate the growth inhibition effects of senescence while limiting its detrimental effects are believed to have great clinical potential. In this review article, we first review the current knowledge of the pro- and antitumorigeneic functions of senescence and summarize the key roles of telomerase in the regulation of senescence in tumors. Second, we review the current literature regarding the anticancer effects of stilbene compounds that are mediated by the targeting of telomerase and cell senescence. Finally, we provide future perspectives on the clinical utilization of stilbene compounds, especially resveratrol and pterostilbene, as novel cancer therapeutic remedies. We conclude and propose that stilbene compounds may induce senescence and may potentially be used as the therapeutic or adjuvant agents for cancers with high telomerase activity.
Among the various types of photomechanical deformations of organic crystals, photoinduced elongation of millimeter-scale crystals has yet to be demonstrated. Here we report that the millimeter-sized ...crystalline rods of an anthracene–pentiptycene hybrid organic π-system (1) are highly elastic and able to elongate up to 21.6% or 0.40 mm without fragmentation upon undergoing 4 + 4 photodimerization reactions. Both the mechanical and photomechanical effects reveal a strong cohesion of the system, even at the interface of 1 and its photodimer 2 and under the conditions of randomized molecular packing, representing a new class of mechanically adaptive organic crystals.
The combination of EGF, CHIR99021, A83-01, SB431542, VPA, and Y27632 (EGF/CASVY) facilitates the derivation of trophoblast stem (TS) cells from human blastocysts and first-trimester, but not term, ...cytotrophoblasts. The mechanism underlying this chemical induction of TS cells remains elusive. Here we demonstrate that the induction efficiency of cytotrophoblast is determined by functional antagonism of the placental transcription factor GCM1 and the stemness regulator ΔNp63α. ΔNp63α reduces GCM1 transcriptional activity, whereas GCM1 inhibits ΔNp63α oligomerization and autoregulation. EGF/CASVY cocktail activates ΔNp63α, thereby partially inhibiting GCM1 activity and reverting term cytotrophoblasts into stem cells. By applying hypoxia condition, we can further reduce GCM1 activity and successfully induce term cytotrophoblasts into TS cells. Consequently, we identify mitochondrial creatine kinase 1 (CKMT1) as a key GCM1 target crucial for syncytiotrophoblast differentiation and reveal decreased CKMT1 expression in preeclampsia. Our study delineates the molecular underpinnings of trophoblast stemness and differentiation and an efficient method to establish TS cells from term placentas.
The sleep and circadian rhythm patterns associated with smartphone use, which are influenced by mental activities, might be closely linked to sleep quality and depressive symptoms, similar to the ...conventional actigraphy-based assessments of physical activity.
The primary objective of this study was to develop app-defined circadian rhythm and sleep indicators and compare them with actigraphy-derived measures. Additionally, we aimed to explore the clinical correlations of these indicators in individuals with insomnia and healthy controls.
The mobile app "Rhythm" was developed to record smartphone use time stamps and calculate circadian rhythms in 33 patients with insomnia and 33 age- and gender-matched healthy controls, totaling 2097 person-days. Simultaneously, we used standard actigraphy to quantify participants' sleep-wake cycles. Sleep indicators included sleep onset, wake time (WT), wake after sleep onset (WASO), and the number of awakenings (NAWK). Circadian rhythm metrics quantified the relative amplitude, interdaily stability, and intradaily variability based on either smartphone use or physical activity data.
Comparisons between app-defined and actigraphy-defined sleep onsets, WTs, total sleep times, and NAWK did not reveal any significant differences (all P>.05). Both app-defined and actigraphy-defined sleep indicators successfully captured clinical features of insomnia, indicating prolonged WASO, increased NAWK, and delayed sleep onset and WT in patients with insomnia compared with healthy controls. The Pittsburgh Sleep Quality Index scores were positively correlated with WASO and NAWK, regardless of whether they were measured by the app or actigraphy. Depressive symptom scores were positively correlated with app-defined intradaily variability (β=9.786, SD 3.756; P=.01) and negatively correlated with actigraphy-based relative amplitude (β=-21.693, SD 8.214; P=.01), indicating disrupted circadian rhythmicity in individuals with depression. However, depressive symptom scores were negatively correlated with actigraphy-based intradaily variability (β=-7.877, SD 3.110; P=.01) and not significantly correlated with app-defined relative amplitude (β=-3.859, SD 12.352; P=.76).
This study highlights the potential of smartphone-derived sleep and circadian rhythms as digital biomarkers, complementing standard actigraphy indicators. Although significant correlations with clinical manifestations of insomnia were observed, limitations in the evidence and the need for further research on predictive utility should be considered. Nonetheless, smartphone data hold promise for enhancing sleep monitoring and mental health assessments in digital health research.
PurposeThis paper explores how Industry 4.0 facilitates small and medium-sized enterprises (SMEs) in emerging markets to gain and maintain organizational legitimacy from the government and market and ...capture value from circular economy (CE) adoption in their businesses.Design/methodology/approachThe authors conduct an in-depth, multistakeholder case study in an SME in China’s hazardous waste recycling and re-utilization industry and apply a qualitative analysis.FindingsThe findings show that Industry 4.0 could facilitate SMEs to gain organizational legitimacy through two mechanisms, namely conforming and transcending. Conforming results in baseline-level outcomes to obtain legitimacy while transcending leads to ecosystem value-cocreation, which goes beyond government expectations and reinforces SMEs' legitimacy.Originality/valueThe authors validated the enabling role of Industry 4.0 in CE adoption in SMEs and have generated legitimation processes and strategies that facilitate SMEs to capture value from CE adoption.
Detecting bacteria in clinical samples without using time-consuming culture processes would allow rapid diagnoses. Such a culture-free detection method requires the capture and analysis of bacteria ...from a body fluid, which are usually of complicated composition. Here we show that coating Ag-nanoparticle arrays with vancomycin (Van) can provide label-free analysis of bacteria via surface-enhanced Raman spectroscopy (SERS), leading to a ~1,000-fold increase in bacteria capture, without introducing significant spectral interference. Bacteria from human blood can be concentrated onto a microscopic Van-coated area while blood cells are excluded. Furthermore, a Van-coated substrate provides distinctly different SERS spectra of Van-susceptible and Van-resistant Enterococcus, indicating its potential use for drug-resistance tests. Our results represent a critical step towards the creation of SERS-based multifunctional biochips for rapid culture- and label-free detection and drug-resistant testing of microorganisms in clinical samples.
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