A parametric symmetry breaking transducer

Force detectors rely on resonators to transduce forces into a readable signal. Usually these resonators operate in the linear regime and their signal appears amidst a competing background comprising thermal or quantum fluctuations as well as readout noise. Here, we demonstrate that a parametric symmetry breaking transduction leads to a novel and robust nonlinear force detection in the presence of noise. The force signal is encoded in the frequency at which the system jumps between two phase states which are inherently protected against phase noise. Consequently, the transduction effectively decouples from readout noise channels. For a controlled demonstration of the method, we experiment with a macroscopic doubly-clamped string. Our method provides a promising new paradigm for high-precision force detection.Comment: 7 pages, 5 figure

Low inbreeding and high pollen dispersal distances in populations of two Amazonian Forest tree species.

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Discrete Laplace Cycles of Period Four

We study discrete conjugate nets whose Laplace sequence is of period four. Corresponding points of opposite nets in this cyclic sequence have equal osculating planes in different net directions, that is, they correspond in an asymptotic transformation. We show that this implies that the connecting lines of corresponding points form a discrete W-congruence. We derive some properties of discrete Laplace cycles of period four and describe two explicit methods for their construction

The Emperor's new clothes: PDE5 and the heart

Phosphodiesterase-5 (PDE5) is highly expressed in the pulmonary vasculature, but its expression in the myocardium is controversial. Cyclic guanosine monophosphate (cGMP) activates protein kinase G (PKG), which has been hypothesized to blunt cardiac hypertrophy and negative remodeling in heart failure. Although PDE5 has been suggested to play a significant role in the breakdown of cGMP in cardiomyocytes and hence PKG regulation in the myocardium, the RELAX trial, which tested effect of PDE5 inhibition on exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF) failed to show a beneficial effect. These results highlight the controversy regarding the role and expression of PDE5 in the healthy and failing heart. This study used one- and two-dimensional electrophoresis and Western blotting to examine PDE5 expression in mouse (before and after trans-aortic constriction), dog (control and HFpEF) as well as human (healthy and failing) heart. We were unable to detect PDE5 in any cardiac tissue lysate, whereas PDE5 was present in the murine and bovine lung samples used as positive controls. These results indicate that if PDE5 is expressed in cardiac tissue, it is present in very low quantities, as PDE5 was not detected in either humans or any model of heart failure examined. Therefore in cardiac muscle, it is unlikely that PDE5 is involved the regulation of cGMP-PKG signaling, and hence PDE5 does not represent a suitable drug target for the treatment of cardiac hypertrophy. These results highlight the importance of rigorous investigation prior to clinical trial design

An off-board quantum point contact as a sensitive detector of cantilever motion

Recent advances in the fabrication of microelectromechanical systems (MEMS) and their evolution into nanoelectromechanical systems (NEMS) have allowed researchers to measure extremely small forces, masses, and displacements. In particular, researchers have developed position transducers with resolution approaching the uncertainty limit set by quantum mechanics. The achievement of such resolution has implications not only for the detection of quantum behavior in mechanical systems, but also for a variety of other precision experiments including the bounding of deviations from Newtonian gravity at short distances and the measurement of single spins. Here we demonstrate the use of a quantum point contact (QPC) as a sensitive displacement detector capable of sensing the low-temperature thermal motion of a nearby micromechanical cantilever. Advantages of this approach include versatility due to its off-board design, compatibility with nanoscale oscillators, and, with further development, the potential to achieve quantum limited displacement detection.Comment: 5 pages, 5 figure

Hybrid Mechanical Systems

We discuss hybrid systems in which a mechanical oscillator is coupled to another (microscopic) quantum system, such as trapped atoms or ions, solid-state spin qubits, or superconducting devices. We summarize and compare different coupling schemes and describe first experimental implementations. Hybrid mechanical systems enable new approaches to quantum control of mechanical objects, precision sensing, and quantum information processing.Comment: To cite this review, please refer to the published book chapter (see Journal-ref and DOI). This v2 corresponds to the published versio

Universal Vectorial and Ultrasensitive Nanomechanical Force Field Sensor

Miniaturization of force probes into nanomechanical oscillators enables ultrasensitive investigations of forces on dimensions smaller than their characteristic length scale. Meanwhile it also unravels the force field vectorial character and how its topology impacts the measurement. Here we expose an ultrasensitive method to image 2D vectorial force fields by optomechanically following the bidimensional Brownian motion of a singly clamped nanowire. This novel approach relies on angular and spectral tomography of its quasi frequency-degenerated transverse mechanical polarizations: immersing the nanoresonator in a vectorial force field does not only shift its eigenfrequencies but also rotate eigenmodes orientation as a nano-compass. This universal method is employed to map a tunable electrostatic force field whose spatial gradients can even take precedence over the intrinsic nanowire properties. Enabling vectorial force fields imaging with demonstrated sensitivities of attonewton variations over the nanoprobe Brownian trajectory will have strong impact on scientific exploration at the nanoscale

Nuclear Magnetic Resonance Imaging with 90 nm Resolution

Magnetic resonance imaging, based on the manipulation and detection of nuclear spins, is a powerful imaging technique that typically operates on the scale of millimeters to microns. Using magnetic resonance force microscopy, we have demonstrated that magnetic resonance imaging of nuclear spins can be extended to a spatial resolution better than 100 nm. The two-dimensional imaging of 19F nuclei was done on a patterned CaF2 test object, and was enabled by a detection sensitivity of roughly 1200 nuclear spins. To achieve this sensitivity, we developed high-moment magnetic tips that produced field gradients up to 1.4x10^6 T/m, and implemented a measurement protocol based on force-gradient detection of naturally occurring spin fluctuations. The resulting detection volume of less than 650 zl represents 60,000x smaller volume than previous NMR microscopy and demonstrates the feasibility of pushing magnetic resonance imaging into the nanoscale regime.Comment: 24 pages, 5 figure

Prevalence and Outcomes for Heavily Treatment-Experienced (HTE) Individuals Living with Human Immunodeficiency Virus in a European Cohort

BACKGROUND: Although antiretroviral treatments have improved survival of persons living with HIV, their long-term use may limit available drug options. We estimated the prevalence of heavily treatment-experienced (HTE) status and the potential clinical consequences of becoming HTE. SETTING: EuroSIDA, a European multicentre prospective cohort study. METHODS: A composite definition for HTE was developed, based on estimates of antiretroviral resistance and prior exposure to specific antiretroviral regimens. Risks of progressing to clinical outcomes were assessed by Poisson regression, comparing every HTE individual with three randomly-selected controls who never became HTE. RESULTS: Of 15,570 individuals under follow-up in 2010-2016, 1617 (10.4%, 95% CI 9.9-10.9%) were classified as HTE. 1093 individuals became HTE during prospective follow-up (HTE incidence rate 1.76, CI 1.66-1.87 per 100 person-years of follow-up). The number of HTE individuals was highest in West/Central Europe (636/4019 persons, 15.7%) and lowest in East Europe (26/2279 persons, 1.1%). Although most HTE individuals maintained controlled viral loads (<400 copies/ml), many had low CD4 counts (≤350 cells/µl). After controlling for age, immunological parameters and pre-existing comorbidities, HTE status was not associated with the risk of new AIDS (adjusted incidence rate ratio, aIRR 1.44, CI 0.86-2.40, p = 0.16) or non-AIDS clinical events (aIRR 0.96, CI 0.74-1.25, p = 0.77). CONCLUSIONS: HTE prevalence increased with time. After adjusting for key confounding factors, there was no evidence for an increased risk of new AIDS or non-AIDS clinical events in HTE. Additional therapeutic options and effective management of comorbidities remain important to reduce clinical complications in HTE individuals