Europe’s pilot line on fully depleted silicon-on-insulator technology (FAMES)
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Flexible micromachined ultrasound transducers (MUTs) for biomedical applications
The use of bulk piezoelectric transducer arrays in medical imaging is a well-established technology that operates based on thickness mode piezoelectric vibration. Meanwhile, advancements in fabrication techniques have led to the emergence of micromachined alternatives, namely, piezoelectric micromachined ultrasound transducer (PMUT) and capacitive micromachined ultrasound transducer (CMUT). These devices operate in flexural mode using piezoelectric thin films and electrostatic forces, respectively. In addition, the development of flexible ultrasound transducers based on these principles has opened up new possibilities for biomedical applications, including biomedical imaging, sensing, and stimulation. This review provides a detailed discussion of the need for flexible micromachined ultrasound transducers (MUTs) and potential applications, their specifications, materials, fabrication, and electronics integration. Specifically, the review covers fabrication approaches and compares the performance specifications of flexible PMUTs and CMUTs, including resonance frequency, sensitivity, flexibility, and other relevant factors. Finally, the review concludes with an outlook on the challenges and opportunities associated with the realization of efficient MUTs with high performance and flexibility.
Targeting aldolase A in hepatocellular carcinoma leads to imbalanced glycolysis and energy stress due to uncontrolled FBP accumulation
Increased glycolytic flux is a hallmark of cancer; however, an increasing body of evidence indicates that glycolytic ATP production may be dispensable in cancer, as metabolic plasticity allows cancer cells to readily adapt to disruption of glycolysis by increasing ATP production via oxidative phosphorylation. Using functional genomic screening, we show here that liver cancer cells show a unique sensitivity toward aldolase A (ALDOA) depletion. Targeting glycolysis by disrupting the catalytic activity of ALDOA led to severe energy stress and cell cycle arrest in murine and human hepatocellular carcinoma cell lines. With a combination of metabolic flux analysis, metabolomics, stable-isotope tracing and mathematical modelling, we demonstrate that inhibiting ALDOA induced a state of imbalanced glycolysis in which the investment phase outpaced the payoff phase. Targeting ALDOA effectively converted glycolysis from an energy producing into an energy-consuming process. Moreover, we found that depletion of ALDOA extended survival and reduced cancer cell proliferation in an animal model of hepatocellular carcinoma. Thus, our findings indicate that induction of imbalanced glycolysis by targeting ALDOA presents a unique opportunity to overcome the inherent metabolic plasticity of cancer cells.
Crystal structures of monomeric BsmI restriction endonuclease reveal coordinated sequential cleavage of two DNA strands
BsmI, a thermophilic Type IIS restriction endonuclease from Bacillus stearothermophilus, presents a unique structural composition, housing two distinct active sites within a single monomer. Recognition of the non-symmetrical 5’-GAATGC-3’ sequence enables precise cleavage of the top and bottom DNA strands. Synthetic biology interventions have led to the transformation of BsmI into Nb.BsmI, a nicking endonuclease. Here we introduce Nt*.BsmI, tailored for top-strand cleavage, which is inactive on standard double-stranded DNA, but active on bottom-strand nicked DNA, suggesting a sequential cleavage mechanism. Crystallographic structures of pre- and post-reactive complexes with cognate DNA show one major conformational change, a retractable loop possibly governing sequential active site accessibility. The x-ray structures reveal the position of the divalent metal ions in the active sites and the DNA:protein interactions, while the models predicted by Alphafold3 are incorrect. This comprehensive structural and functional study lays a foundation for rational enzyme redesign and potential applications in biotechnology.
No evidence for decision fatigue using large-scale field data from healthcare
Decision fatigue is the idea that making decisions is mentally demanding and eventually leads to deteriorated decision quality. Many studies report results that appear consistent with decision fatigue. However, most of this evidence comes from observed sequential patterns using retrospective designs, without preregistration or external validation and with low precision in how decision fatigue is operationalized. Here we conducted an empirical test of decision fatigue using large-scale, high-resolution data on healthcare professionals’ medical judgments at a national telephone triage and medical advice service. This is a suitable setting for testing decision fatigue because the work is both hard and repetitive, yet qualified, and the variation in scheduling produced a setting where level of fatigue could be regarded as near random for some segments of the data. We hypothesized increased use of heuristics, more specifically convergence toward personal defaults in case judgments, and higher assigned urgency ratings with fatigue. We tested these hypotheses using one-sided Bayes Factors computed from underlying Bayesian generalized mixed models with random intercepts. The results consistently showed relative support for the statistical null hypothesis of no difference in decision-making depending on fatigue (BF0+ > 22 for all main tests). We thus found no evidence for decision fatigue. Whereas these results don’t preclude the existence of a weaker or more nuanced version of decision fatigue or more context-specific effects, they cast serious doubt on the empirical relevance of decision fatigue as a domain general effect for sequential decisions in healthcare and elsewhere.
Community composition and physiological plasticity control microbial carbon storage across natural and experimental soil fertility gradients
Many microorganisms synthesise carbon (C)-rich compounds under resource deprivation. Such compounds likely serve as intracellular C-storage pools that sustain the activities of microorganisms growing on stoichiometrically imbalanced substrates, making them potentially vital to the function of ecosystems on infertile soils. We examined the dynamics and drivers of three putative C-storage compounds (neutral lipid fatty acids [NLFAs], polyhydroxybutyrate [PHB], and trehalose) across a natural gradient of soil fertility in eastern Australia. Together, NLFAs, PHB, and trehalose corresponded to 8.5–40% of microbial C and 0.06–0.6% of soil organic C. When scaled to “structural” microbial biomass (indexed by polar lipid fatty acids; PLFAs), NLFA and PHB allocation was 2–3-times greater in infertile soils derived from ironstone and sandstone than in comparatively fertile basalt- and shale-derived soils. PHB allocation was positively correlated with belowground biological phosphorus (P)-demand, while NLFA allocation was positively correlated with fungal PLFA : bacterial PLFA ratios. A complementary incubation revealed positive responses of respiration, storage, and fungal PLFAs to glucose, while bacterial PLFAs responded positively to PO43-. By comparing these results to a model of microbial C-allocation, we reason that NLFA primarily served the “reserve” storage mode for C-limited taxa (i.e., fungi), while the variable portion of PHB likely served as “surplus” C-storage for P-limited bacteria. Thus, our findings reveal a convergence of community-level processes (i.e., changes in taxonomic composition that underpin reserve-mode storage dynamics) and intracellular mechanisms (e.g., physiological plasticity of surplus-mode storage) that drives strong, predictable community-level microbial C-storage dynamics across gradients of soil fertility and substrate stoichiometry.
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