102 research outputs found
Non-white frequency noise in spin torque oscillators and its effect on spectral linewidth
We measure the power spectral density of frequency fluctuations in
nanocontact spin torque oscillators over time scales up to 50 ms. We use a
mixer to convert oscillator signals ranging from 10 GHz to 40 GHz into a band
near 70 MHz before digitizing the time domain waveform. We analyze the waveform
using both zero crossing time stamps and a sliding Fourier transform, discuss
the different limitations and advantages of these two methods, and combine them
to obtain a frequency noise spectrum spanning more than five decades of Fourier
frequency . For devices having a free layer consisting of either a single
NiFe layer or a Co/Ni multilayer we find a
frequency noise spectrum that is white at large and varies as \emph{}
at small . The crossover frequency ranges from \approx\unit[10^{4}]{Hz} to
\approx\unit[10^{6}]{Hz} and the component is stronger in the
multilayer devices. Through actual and simulated spectrum analyzer
measurements, we show that frequency noise causes both broadening and a
change in shape of the oscillator's spectral line as measurement time
increases. Our results indicate that the long term stability of spin torque
oscillators cannot be accurately predicted from models based on thermal (white)
noise sources
Theory of Magnetodynamics Induced by Spin Torque in Perpendicularly Magnetized Thin Films
A nonlinear model of spin wave excitation using a point contact in a thin
ferromagnetic film is introduced. Large-amplitude magnetic solitary waves are
computed, which help explain recent spin-torque experiments. Numerical
simulations of the fully nonlinear model predict excitation frequencies in
excess of 0.2 THz for contact diameters smaller than 6 nm. Simulations also
predict a saturation and red shift of the frequency at currents large enough to
invert the magnetization under the point contact. The theory is approximated by
a cubic complex Ginzburg-Landau type equation. The mode's nonlinear frequency
shift is found by use of perturbation techniques, whose results agree with
those of direct numerical simulations.Comment: 5 pages, 4 figures, submitted to PR
Experience of primary care for people with HIV: a mixed-method analysis
Background Advances in treatment have transformed HIV into a long-term condition (LTC), presenting fresh challenges for health services, HIV specialists and general practitioners (GPs). Aim To explore the experience of people living with HIV (PLHIV) regarding using their GPs. Design and setting A mixed-method analysis using data from two sources: a nationally-representative survey of PLHIV and a qualitative study with London-based PLHIV. Methods Univariate logistic regression for quantitative data and Framework analysis for qualitative data. Results The survey had 4,422 participants; the qualitative study included 52 participants. In both studies, GP registration and HIV status disclosure were high. Similar to general population trends, recent GP use was associated with poor self-rated health status, co-morbidities, older age and lower socioeconomic status. Two-thirds reported a good experience with GPs; a lower proportion felt comfortable asking HIV-related questions. Actual or perceived HIV stigma were consistently associated with poor satisfaction. In the interviews, participants with additional LTCs valued sensitive and consistent support from GPs. Some anticipated, and sometimes experienced, problems relating to HIV status, GPs’ limited experience and time to manage their complex needs. Sometimes they took their own initiatives to facilitate coordination and communication. For PLHIV, a ‘good’ GP offered continuity and took time to know and accept them without judgement. Conclusion We suggest clarification of roles and provision of relevant support to build confidence in GPs and primary care staff to care for PLHIV. As PLHIV population ages, there is a strong need to develop trusting patient/GP relationships and HIV-friendly GP practices
Current-Driven Microwave Dynamics in Magnetic Point Contacts as a Function of Applied Field Angle
We have measured microwave frequency, current-driven magnetization dynamics
in point contacts made to Co90Fe10/Cu/ Ni80Fe20 spin valves as a function of
applied field strength and angle relative to the film plane. As the field
direction is varied from parallel to nearly perpendicular, the device power
output increases by roughly two orders of magnitude while the frequencies of
the excitations decrease. For intermediate angles the excited frequency does
not monotonically vary with applied current and also exhibits abrupt,
current-dependent jumps. For certain ranges of current, and applied field
strength and direction, the excitation linewidths decrease to a few megahertz,
leading to quality factors over 18,000
Direct-Current Induced Dynamics in Co90Fe10/Ni80Fe20 Point Contacts
We have directly measured coherent high-frequency magnetization dynamics in
ferromagnet films induced by a spin-polarized DC current. The precession
frequency can be tuned over a range of several gigahertz, by varying the
applied current. The frequencies of excitation also vary with applied field,
resulting in a microwave oscillator that can be tuned from below 5 GHz to above
40 GHz. This novel method of inducing high-frequency dynamics yields
oscillations having quality factors from 200 to 800. We compare our results
with those from single-domain simulations of current-induced dynamics
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Metabolic gatekeeper function of B-lymphoid transcription factors.
B-lymphoid transcription factors, such as PAX5 and IKZF1, are critical for early B-cell development, yet lesions of the genes encoding these transcription factors occur in over 80% of cases of pre-B-cell acute lymphoblastic leukaemia (ALL). The importance of these lesions in ALL has, until now, remained unclear. Here, by combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, we identify a novel B-lymphoid program for transcriptional repression of glucose and energy supply. Our metabolic analyses revealed that PAX5 and IKZF1 enforce a state of chronic energy deprivation, resulting in constitutive activation of the energy-stress sensor AMPK. Dominant-negative mutants of PAX5 and IKZF1, however, relieved this glucose and energy restriction. In a transgenic pre-B ALL mouse model, the heterozygous deletion of Pax5 increased glucose uptake and ATP levels by more than 25-fold. Reconstitution of PAX5 and IKZF1 in samples from patients with pre-B ALL restored a non-permissive state and induced energy crisis and cell death. A CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets identified the products of NR3C1 (encoding the glucocorticoid receptor), TXNIP (encoding a glucose-feedback sensor) and CNR2 (encoding a cannabinoid receptor) as central effectors of B-lymphoid restriction of glucose and energy supply. Notably, transport-independent lipophilic methyl-conjugates of pyruvate and tricarboxylic acid cycle metabolites bypassed the gatekeeper function of PAX5 and IKZF1 and readily enabled leukaemic transformation. Conversely, pharmacological TXNIP and CNR2 agonists and a small-molecule AMPK inhibitor strongly synergized with glucocorticoids, identifying TXNIP, CNR2 and AMPK as potential therapeutic targets. Furthermore, our results provide a mechanistic explanation for the empirical finding that glucocorticoids are effective in the treatment of B-lymphoid but not myeloid malignancies. Thus, B-lymphoid transcription factors function as metabolic gatekeepers by limiting the amount of cellular ATP to levels that are insufficient for malignant transformation
Polycation-Ï€ Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family
Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al
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