Strong gate coupling of high-Q nanomechanical resonators

The detection of mechanical vibrations near the quantum limit is a formidable challenge since the displacement becomes vanishingly small when the number of phonon quanta tends towards zero. An interesting setup for on-chip nanomechanical resonators is that of coupling them to electrical microwave cavities for detection and manipulation. Here we show how to achieve a large cavity coupling energy of up to (2 \pi) 1 MHz/nm for metallic beam resonators at tens of MHz. We used focused ion beam (FIB) cutting to produce uniform slits down to 10 nm, separating patterned resonators from their gate electrodes, in suspended aluminum films. We measured the thermomechanical vibrations down to a temperature of 25 mK, and we obtained a low number of about twenty phonons at the equilibrium bath temperature. The mechanical properties of Al were excellent after FIB cutting and we recorded a quality factor of Q ~ 3 x 10^5 for a 67 MHz resonator at a temperature of 25 mK. Between 0.2K and 2K we find that the dissipation is linearly proportional to the temperature.Comment: 6 page

rf-electrometer using a carbon nanotube resonant tunneling transistor

We have studied resonant tunneling transistors (RTT) made of single-walled carbon nanotube quantum dots in the Fabry–Pérot regime. We show sensitivity to input charge as high as 5×10 exp −6 e/Hz1/2 with a carrier frequency of 719 MHz at 4.2 K. This result is comparable to the best values of charge sensitivity so far reported for radio frequency single electron transistors (rf-SET). Unlike SETs, whose operating temperature is limited as Coulomb blockade vanishes as 1/T, a RTT can operate at higher temperatures, since the dephasing length lϕ∝1/T exp 2/exp 3.Peer reviewe

De Novo Lipogenesis-Related Monounsaturated Fatty Acids in the Blood Are Associated with Cardiovascular Risk Factors in HFpEF Patients

De novo lipogenesis (DNL)-related monounsaturated fatty acids (MUFAs) in the blood are associated with incident heart failure (HF). This observation's biological plausibility may be due to the potential of these MUFAs to induce proinflammatory pathways, endoplasmic reticulum stress, and insulin resistance, which are pathophysiologically relevant in HF. The associations of circulating MUFAs with cardiometabolic phenotypes in patients with heart failure with a preserved ejection fraction (HFpEF) are unknown. In this secondary analysis of the Aldosterone in Diastolic Heart Failure trial, circulating MUFAs were analysed in 404 patients using the HS-Omega-3-Index$^{®}$ methodology. Patients were 67 ± 8 years old, 53% female, NYHA II/III (87/13%). The ejection fraction was ≥50%, E/e' 7.1 ± 1.5, and the median NT-proBNP 158 ng/L (IQR 82-298). Associations of MUFAs with metabolic, functional, and echocardiographic patient characteristics at baseline/12 months follow-up (12 mFU) were analysed using Spearman's correlation coefficients and linear regression analyses, using sex/age as covariates. Circulating levels of C16:1n7 and C18:1n9 were positively associated with BMI/truncal adiposity and associated traits (dysglycemia, atherogenic dyslipidemia, and biomarkers suggestive of non-alcoholic-fatty liver disease). They were furthermore inversely associated with functional capacity at baseline/12 mFU. In contrast, higher levels of C20:1n9 and C24:1n9 were associated with lower cardiometabolic risk and higher exercise capacity at baseline/12 mFU. In patients with HFpEF, circulating levels of individual MUFAs were differentially associated with cardiovascular risk factors. Our findings speak against categorizing FA based on physicochemical properties. Circulating MUFAs may warrant further investigation as prognostic markers in HFpEF

Trans-fatty acid blood levels of industrial but not natural origin are associated with cardiovascular risk factors in patients with HFpEF: a secondary analysis of the Aldo-DHF trial

BACKGROUND Industrially processed trans-fatty acids (IP-TFA) have been linked to altered lipoprotein metabolism, inflammation and increased NT-proBNP. In patients with heart failure with preserved ejection fraction (HFpEF), associations of TFA blood levels with patient characteristics are unknown. METHODS This is a secondary analysis of the Aldo-DHF-RCT. From 422 patients, individual blood TFA were analyzed at baseline in n = 404 using the HS-Omega-3-Index$^{®}$ methodology. Patient characteristics were: 67 ± 8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥ 50%, E/e' 7.1 ± 1.5; NT-proBNP 158 ng/L (IQR 82-298). A principal component analysis was conducted but not used for further analysis as cumulative variance for the first two PCs was low. Spearman's correlation coefficients as well as linear regression analyses, using sex and age as covariates, were used to describe associations of whole blood TFA with metabolic phenotype, functional capacity, echocardiographic markers for LVDF and neurohumoral activation at baseline and after 12 months. RESULTS Blood levels of the naturally occurring TFA C16:1n-7t were inversely associated with dyslipidemia, body mass index/truncal adiposity, surrogate markers for non-alcoholic fatty liver disease and inflammation at baseline/12 months. Conversely, IP-TFA C18:1n9t, C18:2n6tt and C18:2n6tc were positively associated with dyslipidemia and isomer C18:2n6ct with dysglycemia. C18:2n6tt and C18:2n6ct were inversely associated with submaximal aerobic capacity at baseline/12 months. No significant association was found between TFA and cardiac function. CONCLUSIONS In HFpEF patients, higher blood levels of IP-TFA, but not naturally occurring TFA, were associated with dyslipidemia, dysglycemia and lower functional capacity. Blood TFAs, in particular C16:1n-7t, warrant further investigation as prognostic markers in HFpEF. Higher blood levels of industrially processed TFA, but not of the naturally occurring TFA C16:1n-7t, are associated with a higher risk cardiometabolic phenotype and prognostic of lower aerobic capacity in patients with HFpEF

Liberating Intelligent Machines with Financial Instruments

In science fiction, Isaac Asimov's three laws of robotics, as presented in his novel I, Robot, are the classical starting point for machine responsibility analysis.1 Machine ethics research has widely followed Asimov's example2. Murphy and Woods3 propose alternative laws inspired by Asimov's original laws that emphasize a developer’s view on the ethics of robotics. In these works, machine responsibility is presented from the ethical point of view, but product liability issues are mostly absent, as is legal analysis. The present state of robot legal liability issues is to some extent described in existing literature.4 This paper addresses responsible robotics from a legal perspective. However, instead of focusing on ethical considerations elaborated in philosophy and Artificial Intelligence (AI)5 communities6, the legal liability risks related to inherently error-prone intelligent machines are considered and a solution combining legal and economical components is proposed. Because of the technological difficulties in creating perfectly functioning machines and the cognitive element inherent in intelligent machines and machine interactions, we propose a new kind of legal approach, i.e. a financial instrument liberating the machine. In this framework, a machine can become an ultimate machine by emancipating itself from its manufacturer/owner/operator. This can be achieved through the creation of a legal framework around this ultimate machine that in itself has economic value. We start this article by assessing the liability risks related to intelligent machines. Currently, the manufacturer or operator is held liable depending on the circumstances. Thereafter we will examine the management of the risks by technical and legal means, i.e. by means of liability stocks liberating the machine. The article relates to the European context. However, the solution can easily be adapted to other jurisdictions

The Effects of Cholesterol Oxidation on Erythrocyte Plasma Membranes: A Monolayer Study

This is the final version. Available on open access from MDPI via the DOI in this recordData Availability Statement: All data are available from the corresponding authors.Cholesterol plays a key role in the molecular and mesoscopic organisation of lipid membranes and it is expected that changes in its molecular structure (e.g., through environmental factors such as oxidative stress) may affect adversely membrane properties and function. In this study, we present evidence that oxidation of cholesterol has significant effects on the mechanical properties, molecular and mesoscopic organisation and lipid–sterol interactions in condensed monolayers composed of the main species found in the inner leaflet of the erythrocyte membrane. Using a combination of experimental methods (static area compressibility, surface dilatational rheology, fluorescence microscopy, and surface sensitive X-ray techniques) and atomistic molecular dynamics simulations, we show that oxidation of cholesterol to 7-ketocholesterol leads to stiffening of the monolayer (under both static and dynamic conditions), significant changes in the monolayer microdomain organisation, disruption in the van der Waals, electrostatic and hydrophobic interactions between the sterol and the other lipid species, and the lipid membrane hydration. Surface sensitive X-ray techniques reveal that, whilst the molecular packing mode is not significantly affected by cholesterol oxidation in these condensed phases, there are subtle changes in membrane thickness and a significant decrease in the coherence length in monolayers containing 7-ketocholesterol.Engineering and Physical Sciences Research Council (EPSRC

A pilot study: tail tip lesions in dairy cows – an unnoticed animal welfare issue?

The welfare of dairy cows is becoming increasingly important. While diseases like mastitis and lameness are common ailments, injuries to the tail tip go largely unnoticed. This study aimed to investigate whether tail tip lesions, which are mostly described in beef cattle, also occurred on n=5 dairy farms, along with determining what type and at what frequency. The study consisted of two phases. During the first part of the study, tail tips of 78 dairy cows were examined over a period of 6 months; based on these results, we developed a training card on tail tip lesions in dairy cows, which was used in part two of the study to train further examiners to inspect four more flocks. In total, we collected n=3587 tail records from n=513 Holstein and n= 128 Simmental dairy cows. The overall frequency regarding all types of lesions ranged between 84.0 % (±2.0) and 94.1 % (±1.8) in Holstein herds and between 97.0 % (±2.2) and 99.0 % (±2.2) in Simmental herds. To our knowledge, this is the first investigation of tail tip lesions in German dairy cows. We concluded that tail tip lesions might be a frequent yet unnoticed condition in German dairy cows.</p

Multiple Signals Converge on a Differentiation MAPK Pathway

An important emerging question in the area of signal transduction is how information from different pathways becomes integrated into a highly coordinated response. In budding yeast, multiple pathways regulate filamentous growth, a complex differentiation response that occurs under specific environmental conditions. To identify new aspects of filamentous growth regulation, we used a novel screening approach (called secretion profiling) that measures release of the extracellular domain of Msb2p, the signaling mucin which functions at the head of the filamentous growth (FG) MAPK pathway. Secretion profiling of complementary genomic collections showed that many of the pathways that regulate filamentous growth (RAS, RIM101, OPI1, and RTG) were also required for FG pathway activation. This regulation sensitized the FG pathway to multiple stimuli and synchronized it to the global signaling network. Several of the regulators were required for MSB2 expression, which identifies the MSB2 promoter as a target “hub” where multiple signals converge. Accessibility to the MSB2 promoter was further regulated by the histone deacetylase (HDAC) Rpd3p(L), which positively regulated FG pathway activity and filamentous growth. Our findings provide the first glimpse of a global regulatory hierarchy among the pathways that control filamentous growth. Systems-level integration of signaling circuitry is likely to coordinate other regulatory networks that control complex behaviors