Signal-to-noise ratio enhanced electrode configurations for magnetoelectric cantilever sensors

Magnetoelectric cantilevers consisting of strain-coupled magnetostrictive and piezoelectric (PE) layers are applicable to magnetic-fi eld sens- ing. For the fi rst bending mode, the magnetic fi eld-induced stress distribution is of equal sign along the cantilever length. Thus, a plate- capacitor electrode configuration encompassing the complete PE layer may be used for collecting the strain-induced charge. For higher order modes, stress regions of the opposite sign occur in the cantilever length direction. To prevent charge cancellation and to harvest the piezo- electric induced charge effi ciently, segmented electrodes are employed. This study investigates the effect of the electrode confi gurationon the signal-to-noise ratio (SNR) for higher order bending modes. The charges collected by the electrodes are calculated using a fi nite element method simulation considering the mechanical, electrical, and magnetic properties of the cantilever. By combination with an analytic noise model, taking into account the sensor and amplifi er noise sources, the SNR is obtained. We analyze a 3 mm long, 1 mm wide, and 50 μm thick silicon cantilever with layers of 2 μm magnetostrictive soft amorphous metal (FeCoSiB) and 2 μm piezoelectric aluminum nitride. We demonstrate that an SNR-optimized electrode design yields an SNR improvement by 2.3 dB and 2.4 dB for the second and third bending modes compared to a signal optimized design

Toward community standards and software for whole-cell modeling

Whole-cell (WC) modeling is a promising tool for biological research, bioengineering, and medicine. However, substantial work remains to create accurate, comprehensive models of complex cells. Methods: We organized the 2015 Whole-Cell Modeling Summer School to teach WC modeling and evaluate the need for new WC modeling standards and software by recoding a recently published WC model in SBML. Results: Our analysis revealed several challenges to representing WC models using the current standards. Conclusion: We, therefore, propose several new WC modeling standards, software, and databases. Significance:We anticipate that these new standards and software will enable more comprehensive models

RAD21 Cooperates with Pluripotency Transcription Factors in the Maintenance of Embryonic Stem Cell Identity

For self-renewal, embryonic stem cells (ESCs) require the expression of specific transcription factors accompanied by a particular chromosome organization to maintain a balance between pluripotency and the capacity for rapid differentiation. However, how transcriptional regulation is linked to chromosome organization in ESCs is not well understood. Here we show that the cohesin component RAD21 exhibits a functional role in maintaining ESC identity through association with the pluripotency transcriptional network. ChIP-seq analyses of RAD21 reveal an ESC specific cohesin binding pattern that is characterized by CTCF independent co-localization of cohesin with pluripotency related transcription factors Oct4, Nanog, Sox2, Esrrb and Klf4. Upon ESC differentiation, most of these binding sites disappear and instead new CTCF independent RAD21 binding sites emerge, which are enriched for binding sites of transcription factors implicated in early differentiation. Furthermore, knock-down of RAD21 causes expression changes that are similar to expression changes after Nanog depletion, demonstrating the functional relevance of the RAD21 - pluripotency transcriptional network association. Finally, we show that Nanog physically interacts with the cohesin or cohesin interacting proteins STAG1 and WAPL further substantiating this association. Based on these findings we propose that a dynamic placement of cohesin by pluripotency transcription factors contributes to a chromosome organization supporting the ESC expression program

The masterpieces of John Forbes Nash Jr.

In this set of notes I follow Nash’s four groundbreaking works on real algebraic manifolds, on isometric embeddings of Riemannian manifolds and on the continuity of solutions to parabolic equations. My aim has been to stay as close as possible to Nash’s original arguments, but at the same time present them with a more modern language and notation. Occasionally I have also provided detailed proofs of the points that Nash leaves to the reader

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Theory of magnetoelectric effect in multilayer nanocomposites on a substrate: Resonant bending-mode response

Resonant bending-mode magnetoelectric (ME) coefficients of magnetostrictive-piezoelectric multilayer cantilevers are calculated analytically using a model developed for arbitrary multilayers on a substrate. Without quality factor effects the ME coefficient maxima in the four-dimensional parameter space of layer numbers, layer sequences, piezoelectric volume fractions, and substrate thicknesses are found to be essentially constant for nonzero substrate thickness. Global maxima occur for bilayers without substrates. Vanishing magnetoelectric response regions result from voltage cancellation in piezoelectric layers or absence of bending-mode excitation. They are determined by the neutral plane position in the multilayer stack. With Q-factor effects dominated by viscous air damping ME coefficients strongly increase with cantilever thickness primarily due to increasing resonance frequencies. The results yield a layer specific prediction of ME coefficients, resonance frequencies, and Q-factors in arbitrary multilayers and thus distinction of linear-coupling and Q-factor effects from exchange interaction, interface, or nonlinear ME effects

Static magnetoelectric and magnetoelastic response of composite cantilevers: Theory of short vs. open circuit operation and layer sequence effects

The static bending-mode transverse magnetoelectric effect and the magnetic field-induced bending response of composite cantilevers with thin magnetostrictive (MS), piezoelectric (PE), and substrate (Sub) layers is investigated for the PE layer subjected to open and short circuit conditions. Analytic theories are presented for strain-coupled three layer composites of PE, MS, and Sub layers in all layer sequences. We use constitutive equations with linear coupling of stress, strain, H, E, and D fields and present results for the open and short circuit magnetoelectric and bending responses for arbitrary layer thickness ratios for the FeCoBSi-AlN-Si materials system. Besides a rich sequence dependent behavior the theory predicts great and systematic differences between the open and short circuit magnetoelectric response yielding maxima at similar MS and PE layer thicknesses in the open circuit and near vanishing PE layer thicknesses in the short circuit cases. In contrast, the open vs. short circuit bending response differences are pronounced but much smaller. Layer sequence systematics and implications for static H-field sensors will be discussed