We investigate the synchronization of oscillators based on anharmonic nanoelectromechanical resonators. Our experimental implementation allows unprecedented observation and control of parameters ...governing the dynamics of synchronization. We find close quantitative agreement between experimental data and theory describing reactively coupled Duffing resonators with fully saturated feedback gain. In the synchronized state we demonstrate a significant reduction in the phase noise of the oscillators, which is key for sensor and clock applications. Our work establishes that oscillator networks constructed from nanomechanical resonators form an ideal laboratory to study synchronization--given their high-quality factors, small footprint, and ease of cointegration with modern electronic signal processing technologies.
Three-dimensional (3D) printing is an emerging approach for rapid fabrication of complex tissue structures using cell-loaded bioinks. However, 3D bioprinting has hit a bottleneck in progress because ...of the lack of suitable bioinks that are printable, have high shape fidelity, and are mechanically resilient. In this study, we introduce a new family of nanoengineered bioinks consisting of kappa-carrageenan (κCA) and two-dimensional (2D) nanosilicates (nSi). κCA is a biocompatible, linear, sulfated polysaccharide derived from red algae and can undergo thermo-reversible and ionic gelation. The shear-thinning characteristics of κCA were tailored by nanosilicates to develop a printable bioink. By tuning κCA–nanosilicate ratios, the thermo-reversible gelation of the bioink can be controlled to obtain high printability and shape retention characteristics. The unique aspect of the nanoengineered κCA–nSi bioink is its ability to print physiologically-relevant-scale tissue constructs without requiring secondary supports. We envision that nanoengineered κCA–nanosilicate bioinks can be used to 3D print complex, large-scale, cell-laden tissue constructs with high structural fidelity and tunable mechanical stiffness for regenerative medicine.
Clay nanomaterials are an emerging class of 2D biomaterials of interest due to their atomically thin layered structure, charged characteristics, and well‐defined composition. Synthetic nanoclays are ...plate‐like polyions composed of simple or complex salts of silicic acids with a heterogeneous charge distribution and patchy interactions. Due to their biocompatible characteristics, unique shape, high surface‐to‐volume ratio, and charge, nanoclays are investigated for various biomedical applications. Here, a critical overview of the physical, chemical, and physiological interactions of nanoclay with biological moieties, including cells, proteins, and polymers, is provided. The state‐of‐the‐art biomedical applications of 2D nanoclay in regenerative medicine, therapeutic delivery, and additive manufacturing are reviewed. In addition, recent developments that are shaping this emerging field are discussed and promising new research directions for 2D nanoclay‐based biomaterials are identified.
The biomedical applications of 2D nanoclay in regenerative medicine, therapeutic delivery, and additive manufacturing are reviewed. An overview on physical, chemical, and physiological interactions of nanoclay with biological moieties including cells, proteins, and polymers is provided. In addition, recent developments that are shaping this emerging field are examined, and promising new research directions for 2D‐nanoclay‐based biomaterials are identified.
Synchronization of oscillators, a phenomenon found in a wide variety of natural and engineered systems, is typically understood through a reduction to a first-order phase model with simplified ...dynamics. Here, by exploiting the precision and flexibility of nanoelectromechanical systems, we examined the dynamics of a ring of quasi-sinusoidal oscillators at and beyond first order. Beyond first order, we found exotic states of synchronization with highly complex dynamics, including weak chimeras, decoupled states, traveling waves, and inhomogeneous synchronized states. Through theory and experiment, we show that these exotic states rely on complex interactions emerging out of networks with simple linear nearest-neighbor coupling. This work provides insight into the dynamical richness of complex systems with weak nonlinearities and local interactions.
In its most basic form an oscillator consists of a resonator driven on resonance, through feedback, to create a periodic signal sustained by a static energy source. The generation of a stable ...frequency, the basic function of oscillators, is typically achieved by increasing the amplitude of motion of the resonator while remaining within its linear, harmonic regime. Contrary to this conventional paradigm, in this Letter we show that by operating the oscillator at special points in the resonator's anharmonic regime we can overcome fundamental limitations of oscillator performance due to thermodynamic noise as well as practical limitations due to noise from the sustaining circuit. We develop a comprehensive model that accounts for the major contributions to the phase noise of the nonlinear oscillator. Using a nanoelectromechanical system based oscillator, we experimentally verify the existence of a special region in the operational parameter space that enables suppressing the most significant contributions to the oscillator's phase noise, as predicted by our model.
Given that cardiovascular safety liabilities remain a major cause of drug attrition during preclinical and clinical development, adverse drug reactions, and post‐approval withdrawal of medicines, the ...Medical Research Council Centre for Drug Safety Science hosted a workshop to discuss current challenges in determining, understanding and addressing ‘Cardiovascular Toxicity of Medicines’. This article summarizes the key discussions from the workshop that aimed to address three major questions: (i) what are the key cardiovascular safety liabilities in drug discovery, drug development and clinical practice? (ii) how good are preclinical and clinical strategies for detecting cardiovascular liabilities? and (iii) do we have a mechanistic understanding of these liabilities? It was concluded that in order to understand, address and ultimately reduce cardiovascular safety liabilities of new therapeutic agents there is an urgent need to:
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Fully characterize the incidence, prevalence and impact of drug‐induced cardiovascular issues at all stages of the drug development process.
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Ascertain the predictive value of existing non‐clinical models and assays towards the clinical outcome.
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Understand the mechanistic basis of cardiovascular liabilities; by addressing areas where it is currently not possible to predict clinical outcome based on preclinical safety data.
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Provide scientists in all disciplines with additional skills to enable them to better integrate preclinical and clinical data and to better understand the biological and clinical significance of observed changes.
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Develop more appropriate, highly relevant and predictive tools and assays to identify and wherever feasible to eliminate cardiovascular safety liabilities from molecules and wherever appropriate to develop clinically relevant and reliable safety biomarkers.
Attitudes are often referred to, researched and considered in the discipline of health education and health promotion. This paper highlights Q methodology as an appropriate and relevant means of ...exploring and studying attitudes within this field. It begins by discussing the difficulties in defining attitude and the problems inherent in attitude measurement. A brief history of Q methodology is given, followed by an explanation of what Q methodology is and the processes involved. This paper argues the case for the use of Q methodology when studying attitudes and justifies why Q methodology should particularly be selected in the study of attitudes within the health field. There are many reasons for this assertion which are explored throughout the paper. The principle one is that Q methodology is a more robust technique, than alternative methods, for the measurement of attitudes and subjective opinion. This paper concludes by proposing that Q methodology is taken up by researchers within health education and health promotion who are concerned with exploring attitudes and subjective opinion.
Transcription of protein-coding genes in trypanosomes is polycistronic and gene expression is primarily regulated by post-transcriptional mechanisms. Sequence motifs in the untranslated regions ...regulate mRNA trans-splicing and RNA stability, yet where UTRs begin and end is known for very few genes. We used high-throughput RNA-sequencing to determine the genome-wide steady-state mRNA levels ('transcriptomes') for ~90% of the genome in two stages of the Trypanosoma brucei life cycle cultured in vitro. Almost 6% of genes were differentially expressed between the two life-cycle stages. We identified 5' splice-acceptor sites (SAS) and polyadenylation sites (PAS) for 6959 and 5948 genes, respectively. Most genes have between one and three alternative SAS, but PAS are more dispersed. For 488 genes, SAS were identified downstream of the originally assigned initiator ATG, so a subsequent in-frame ATG presumably designates the start of the true coding sequence. In some cases, alternative SAS would give rise to mRNAs encoding proteins with different N-terminal sequences. We could identify the introns in two genes known to contain them, but found no additional genes with introns. Our study demonstrates the usefulness of the RNA-seq technology to study the transcriptional landscape of an organism whose genome has not been fully annotated.
Antenatal anxiety symptoms are not only a health problem for the expectant mother. Research has found that maternal anxiety may also have an impact on the developing baby. Therefore, it is important ...to estimate the prevalence of maternal anxiety and associated factors. The current study aims to estimate the prevalence of anxiety symptoms during the first trimester of pregnancy and to identify associated risk factors. Secondly, to investigate other factors associated with anxiety during early pregnancy including fear of childbirth and a preference for cesarean section. In a population-based community sample of 1,175 pregnant women, 916 women (78 %) were investigated in the first trimester (gestation week 8–12). The Hospital Anxiety Depression Scale (HADS-A) was used to measure anxiety symptoms. The prevalence of anxiety symptoms (HADS-A scores ≥8 during pregnancy) was 15.6 % in early pregnancy. Women under 25 years of age were at an increased risk of anxiety symptoms during early pregnancy (OR 2.6, CI 1.7–4.0). Women who reported a language other than Swedish as their native language (OR 4.2, CI 2.7–7.0), reported high school as their highest level of education (OR 1.6, CI 1.1–2.3), were unemployed (OR 3.5, CI 2.1–5.8), used nicotine before pregnancy (OR 1.7, CI 1.1–2.5), and had a self-reported psychiatric history of either depression (OR 3.8, CI 2.6–5.6) or anxiety (OR 5.2, CI 3.5–7.9) before their current pregnancy were all at an increased risk of anxiety symptoms during early pregnancy. Anxiety symptoms during pregnancy increased the rate of fear of birth (OR 3.0, CI 1.9–4.7) and a preference for cesarean section (OR 1.7, CI 1.0–2.8). Caregivers should pay careful attention to history of mental illness to be able to identify women with symptoms of anxiety during early pregnancy. When presenting with symptoms of anxiety, the women might need counseling and or treatment in order to decrease her anxiety.
We study an open quantum system of atoms with a long-range Rydberg interaction, laser driving, and spontaneous emission. Over time, the system occasionally jumps between a state of low Rydberg ...population and a state of high Rydberg population. The jumps are inherently collective, and in fact, exist only for a large number of atoms. We explain how entanglement and quantum measurement enable the jumps, which are otherwise classically forbidden.
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