Minimization of phonon-tunneling dissipation in mechanical resonators

Micro- and nanoscale mechanical resonators have recently emerged as ubiquitous devices for use in advanced technological applications, for example in mobile communications and inertial sensors, and as novel tools for fundamental scientific endeavors. Their performance is in many cases limited by the deleterious effects of mechanical damping. Here, we report a significant advancement towards understanding and controlling support-induced losses in generic mechanical resonators. We begin by introducing an efficient numerical solver, based on the "phonon-tunneling" approach, capable of predicting the design-limited damping of high-quality mechanical resonators. Further, through careful device engineering, we isolate support-induced losses and perform the first rigorous experimental test of the strong geometric dependence of this loss mechanism. Our results are in excellent agreement with theory, demonstrating the predictive power of our approach. In combination with recent progress on complementary dissipation mechanisms, our phonon-tunneling solver represents a major step towards accurate prediction of the mechanical quality factor.Comment: 12 pages, 4 figure

Local Optical Probe of Motion and Stress in a multilayer graphene NEMS

Nanoelectromechanical systems (NEMSs) are emerging nanoscale elements at the crossroads between mechanics, optics and electronics, with significant potential for actuation and sensing applications. The reduction of dimensions compared to their micronic counterparts brings new effects including sensitivity to very low mass, resonant frequencies in the radiofrequency range, mechanical non-linearities and observation of quantum mechanical effects. An important issue of NEMS is the understanding of fundamental physical properties conditioning dissipation mechanisms, known to limit mechanical quality factors and to induce aging due to material degradation. There is a need for detection methods tailored for these systems which allow probing motion and stress at the nanometer scale. Here, we show a non-invasive local optical probe for the quantitative measurement of motion and stress within a multilayer graphene NEMS provided by a combination of Fizeau interferences, Raman spectroscopy and electrostatically actuated mirror. Interferometry provides a calibrated measurement of the motion, resulting from an actuation ranging from a quasi-static load up to the mechanical resonance while Raman spectroscopy allows a purely spectral detection of mechanical resonance at the nanoscale. Such spectroscopic detection reveals the coupling between a strained nano-resonator and the energy of an inelastically scattered photon, and thus offers a new approach for optomechanics

Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae

Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae. Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo. Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses. Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection. In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE. Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone. However lack of eosinophils or MBP-1 actually increased goblet cell mucus production. We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1. These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity

Comparative effectiveness and safety of analgesic medicines for adults with non-specific acute low back pain: systematic review and network meta-analysis

Objective To evaluate the comparative effectiveness and safety of analgesic medicines for acute non-specific low back pain. Design Systematic review and network meta-analysis. Data sources Medline, PubMed, Embase, CINAHL, CENTRAL, ClinicalTrials.gov, clinicialtrialsregister.eu, and World Health Organization’s International Clinical Trials Registry Platform from database inception to 20 February 2022. Eligibility criteria for study selection Randomised controlled trials of analgesic medicines (eg, non-steroidal anti-inflammatory drugs, paracetamol, opioids, anti-convulsant drugs, skeletal muscle relaxants, or corticosteroids) compared with another analgesic medicine, placebo, or no treatment. Adults (≥18 years) who reported acute non-specific low back pain (for less than six weeks). Data extraction and synthesis Primary outcomes were low back pain intensity (0-100 scale) at end of treatment and safety (number of participants who reported any adverse event during treatment). Secondary outcomes were low back specific function, serious adverse events, and discontinuation from treatment. Two reviewers independently identified studies, extracted data, and assessed risk of bias. A random effects network meta-analysis was done and confidence was evaluated by the Confidence in Network Meta-Analysis method. Results 98 randomised controlled trials (15 134 participants, 49% women) included 69 different medicines or combinations. Low or very low confidence was noted in evidence for reduced pain intensity after treatment with tolperisone (mean difference −26.1 (95% confidence intervals −34.0 to −18.2)), aceclofenac plus tizanidine (−26.1 (−38.5 to −13.6)), pregabalin (−24.7 (−34.6 to −14.7)), and 14 other medicines compared with placebo. Low or very low confidence was noted for no difference between the effects of several of these medicines. Increased adverse events had moderate to very low confidence with tramadol (risk ratio 2.6 (95% confidence interval 1.5 to 4.5)), paracetamol plus sustained release tramadol (2.4 (1.5 to 3.8)), baclofen (2.3 (1.5 to 3.4)), and paracetamol plus tramadol (2.1 (1.3 to 3.4)) compared with placebo. These medicines could increase the risk of adverse events compared with other medicines with moderate to low confidence. Moderate to low confidence was also noted for secondary outcomes and secondary analysis of medicine classes. Conclusions The comparative effectiveness and safety of analgesic medicines for acute non-specific low back pain are uncertain. Until higher quality randomised controlled trials of head-to-head comparisons are published, clinicians and patients are recommended to take a cautious approach to manage acute non-specific low back pain with analgesic medicines.MAW was supported by a Postgraduate Scholarship from the National Health and Medical Research Council of Australia, a School of Medical Sciences Top-Up Scholarship from the University of New South Wales, and a PhD Supplementary Scholarship from Neuroscience Research Australia. MKB was supported by a PhD Candidature Scholarship and Supplementary Scholarship from Neuroscience Research Australia. MCF was supported by an Australian Government Research Training Program Scholarship, a PhD Supplementary Scholarship from Neuroscience Research Australia, and the Edward C Dunn Foundation Scholarship. RRNR was supported by the School of Medical Sciences Postgraduate Research Scholarship from the University of New South Wales and a PhD Supplementary Scholarship from Neuroscience Research Australia. HBL was supported by an Australian Government Research Training Program Scholarship. SSh was supported by the International Association for the Study of Pain John J Bonica Postdoctoral Fellowship. CGM was supported by an NHMRC Leadership 3 Fellowship (App 1194283). SMG was supported by a Research Fellowship from the Rebecca L Cooper Foundation. AN was supported by personal fellowship (P400PM_186723) from the Swiss National Science Foundation. This study received project support funding from a 2020 Exercise Physiology Research (Consumables) Grant from the University of New South Wales, which was used to obtain translations of studies published in languages other than English. The funder had played no part in the design, conduct, or analysis of the study

Sideband Cooling Micromechanical Motion to the Quantum Ground State

The advent of laser cooling techniques revolutionized the study of many atomic-scale systems. This has fueled progress towards quantum computers by preparing trapped ions in their motional ground state, and generating new states of matter by achieving Bose-Einstein condensation of atomic vapors. Analogous cooling techniques provide a general and flexible method for preparing macroscopic objects in their motional ground state, bringing the powerful technology of micromechanics into the quantum regime. Cavity opto- or electro-mechanical systems achieve sideband cooling through the strong interaction between light and motion. However, entering the quantum regime, less than a single quantum of motion, has been elusive because sideband cooling has not sufficiently overwhelmed the coupling of mechanical systems to their hot environments. Here, we demonstrate sideband cooling of the motion of a micromechanical oscillator to the quantum ground state. Entering the quantum regime requires a large electromechanical interaction, which is achieved by embedding a micromechanical membrane into a superconducting microwave resonant circuit. In order to verify the cooling of the membrane motion into the quantum regime, we perform a near quantum-limited measurement of the microwave field, resolving this motion a factor of 5.1 from the Heisenberg limit. Furthermore, our device exhibits strong-coupling allowing coherent exchange of microwave photons and mechanical phonons. Simultaneously achieving strong coupling, ground state preparation and efficient measurement sets the stage for rapid advances in the control and detection of non-classical states of motion, possibly even testing quantum theory itself in the unexplored region of larger size and mass.Comment: 13 pages, 7 figure

Delocalized single-photon Dicke states and the Leggett- Garg inequality in solid state systems

We show how to realize a single-photon Dicke state in a large one-dimensional array of two- level systems, and discuss how to test its quantum properties. Realization of single-photon Dicke states relies on the cooperative nature of the interaction between a field reservoir and an array of two-level-emitters. The resulting dynamics of the delocalized state can display Rabi-like oscillations when the number of two-level emitters exceeds several hundred. In this case the large array of emitters is essentially behaving like a mirror-less cavity. We outline how this might be realized using a multiple-quantum-well structure and discuss how the quantum nature of these oscillations could be tested with the Leggett-Garg inequality and its extensions.Comment: 29 pages, 5 figures, journal pape

Factors influencing overweight children's commencement of and continuation in a resistance training program

<p>Abstract</p> <p>Background</p> <p>In light of the child overweight and obesity problem in Australia, resistance training programs have been trialled as an innovative way of assisting children increase lean body mass and reduce body fat. The purpose of this study was to investigate the factors influencing overweight children's participation in a resistance training trial program.</p> <p>Method</p> <p>Parent-child pairs who participated in the trial program were invited to take part in a follow-up individual interview to discuss their program experiences. In total, 22 semi-structured interviews were conducted with 11 parent-child pairs.</p> <p>Results</p> <p>The factors found to be most relevant to program commencement among parents were a desire for their child to lose weight and gain confidence, the proximity of the venue, and no cost for participation. For children, the most relevant factors were the opportunity to build strength and improve fitness and having supportive parents who facilitated program initiation. The factors most relevant to continuation for parents were the quality of the program management, being able to stay for the sessions, the child's improved weight status, coordination, and confidence, and no cost for participation. Weight loss and improved confidence were also motivators for continuation among the children, along with pleasant social interaction with peers and trainers and ongoing parental support.</p> <p>Conclusion</p> <p>Different factors variably influence program commencement and program continuation in both parents and children. This has important implications for future interventions that aim to successfully recruit and retain intervention participants.</p

Editing independent effects of ADARs on the miRNA/siRNA pathways

Adenosine deaminases acting on RNA (ADARs) are best known for altering the coding sequences of mRNA through RNA editing, as in the GluR-B Q/R site. ADARs have also been shown to affect RNA interference (RNAi) and microRNA processing by deamination of specific adenosines to inosine. Here, we show that ADAR proteins can affect RNA processing independently of their enzymatic activity. We show that ADAR2 can modulate the processing of mir-376a2 independently of catalytic RNA editing activity. In addition, in a Drosophila assay for RNAi deaminase-inactive ADAR1 inhibits RNAi through the siRNA pathway. These results imply that ADAR1 and ADAR2 have biological functions as RNA-binding proteins that extend beyond editing per se and that even genomically encoded ADARs that are catalytically inactive may have such functions

Failure of recombinant factor VIIa in a patient with severe polymicrobial sepsis and postoperative uncontrolled intraabdominal bleeding

<p>Abstract</p> <p>Background</p> <p>This report discusses a case of unsuccessful treatment with recombinant factor VIIa (rFVIIa) in off-label use. The need for international guidelines concerning the off-label use of rFVIIa is outlined as well as the need for methods to control the efficacy of rFVIIa objectively.</p> <p>Case presentation</p> <p>54 year old male with severe polymicrobial sepsis due to a perforated diverticulitis of the sigmoid colon and consecutive overt disseminated intravascular coagulation. He suffered severe intraabdominal bleeding after abdominal surgery despite conventional haemostatic support. Repeated applications of factor VIIa temporarily improved coagulation essays but did not stop clinical bleeding. The patient died in multiorgan failure due to septic and haemorrhagic shock.</p> <p>Conclusion</p> <p>Off-label use of rFVIIa could result in more side effects than could be expected from literature because of a publication bias. However for most off-label applications large prospective, randomised and controlled trials to confirm the positive findings are missing. For the future, not only guidelines concerning the off-label use of rFVIIa are urgently needed but also guidelines for monitoring the efficacy of rFVIIa.</p