Understanding Pound-Drever-Hall locking using voltage controlled radio-frequency oscillators: An undergraduate experiment

We have developed a senior undergraduate experiment that illustrates frequency stabilization techniques using radio-frequency electronics. The primary objective is to frequency stabilize a voltage controlled oscillator to a cavity resonance at 800 MHz using the Pound-Drever-Hall method. This technique is commonly applied to stabilize lasers at optical frequencies. By using only radio-frequency equipment it is possible to systematically study aspects of the technique more thoroughly, inexpensively, and free from eye hazards. Students also learn about modular radio-frequency electronics and basic feedback control loops. By varying the temperature of the resonator, students can determine the thermal expansion coefficients of copper, aluminum, and super invar.Comment: 9 pages, 10 figure

Optimized design of a low-resistance electrical conductor for the multimegahertz range

We propose a design for a conductive wire composed of several mutually insulated coaxial conducting shells. With the help of numerical optimization, it is possible to obtain electrical resistances significantly lower than those of a heavy-gauge copper wire or litz wire in the 2–20 MHz range. Moreover, much of the reduction in resistance can be achieved for just a few shells; in contrast, litz wire would need to contain ∼ 10[superscript 4] strands to perform comparably in this frequency range

The Intrinsic Origin of Spin Echoes in Dipolar Solids Generated by Strong Pi Pulses

In spectroscopy, it is conventional to treat pulses much stronger than the linewidth as delta-functions. In NMR, this assumption leads to the prediction that pi pulses do not refocus the dipolar coupling. However, NMR spin echo measurements in dipolar solids defy these conventional expectations when more than one pi pulse is used. Observed effects include a long tail in the CPMG echo train for short delays between pi pulses, an even-odd asymmetry in the echo amplitudes for long delays, an unusual fingerprint pattern for intermediate delays, and a strong sensitivity to pi-pulse phase. Experiments that set limits on possible extrinsic causes for the phenomena are reported. We find that the action of the system's internal Hamiltonian during any real pulse is sufficient to cause the effects. Exact numerical calculations, combined with average Hamiltonian theory, identify novel terms that are sensitive to parameters such as pulse phase, dipolar coupling, and system size. Visualization of the entire density matrix shows a unique flow of quantum coherence from non-observable to observable channels when applying repeated pi pulses.Comment: 24 pages, 27 figures. Revised from helpful referee comments. Added new Table IV, new paragraphs on pages 3 and 1

Double Neutron Star Systems and Natal Neutron Star Kicks

We study the four double neutron star systems found in the Galactic disk in terms of the orbital characteristics of their immediate progenitors and the natal kicks imparted to neutron stars. Analysis of the effect of the second supernova explosion on the orbital dynamics, combined with recent results from simulations of rapid accretion onto neutron stars lead us to conclude that the observed systems could not have been formed had the explosion been symmetric. Their formation becomes possible if kicks are imparted to the radio-pulsar companions at birth. We identify the constraints imposed on the immediate progenitors of the observed double neutron stars and calculate the ranges within which their binary characteristics (orbital separations and masses of the exploding stars) are restricted. We also study the dependence of these limits on the magnitude of the kick velocity and the time elapsed since the second explosion. For each of the double neutron stars, we derive a minimum kick magnitude required for their formation, and for the two systems in close orbits we find it to exceed 200km/s. Lower limits are also set to the center-of-mass velocities of double neutron stars, and we find them to be consistent with the current proper motion observations.Comment: 25 pages, 6 figs (9 parts), 4 tables, AASTeX, Accepted in Ap

Incidence of and predictors for antiseizure medication gaps in Medicare beneficiaries with epilepsy: a retrospective cohort study.

BACKGROUND For the two-thirds of patients with epilepsy who achieve seizure remission on antiseizure medications (ASMs), patients and clinicians must weigh the pros and cons of long-term ASM treatment. However, little work has evaluated how often ASM discontinuation occurs in practice. We describe the incidence of and predictors for sustained ASM fill gaps to measure discontinuation in individuals potentially eligible for ASM withdrawal. METHODS This was a retrospective cohort of Medicare beneficiaries. We included patients with epilepsy by requiring International Classification of Diseases codes for epilepsy/convulsions plus at least one ASM prescription each year 2014-2016, and no acute visit for epilepsy 2014-2015 (i.e., potentially eligible for ASM discontinuation). The main outcome was the first day of a gap in ASM supply (30, 90, 180, or 360 days with no pills) in 2016-2018. We displayed cumulative incidence functions and identified predictors using Cox regressions. RESULTS Among 21,819 beneficiaries, 5191 (24%) had a 30-day gap, 1753 (8%) had a 90-day gap, 803 (4%) had a 180-day gap, and 381 (2%) had a 360-day gap. Predictors increasing the chance of a 180-day gap included number of unique medications in 2015 (hazard ratio [HR] 1.03 per medication, 95% confidence interval [CI] 1.01-1.05) and epileptologist prescribing physician (≥25% of that physician's visits for epilepsy; HR 2.37, 95% CI 1.39-4.03). Predictors decreasing the chance of a 180-day gap included Medicaid dual eligibility (HR 0.75, 95% CI 0.60-0.95), number of unique ASMs in 2015 (e.g., 2 versus 1: HR 0.37, 95% CI 0.30-0.45), and greater baseline adherence (> 80% versus ≤80% of days in 2015 with ASM pill supply: HR 0.38, 95% CI 0.32-0.44). CONCLUSIONS Sustained ASM gaps were rarer than current guidelines may suggest. Future work should further explore barriers and enablers of ASM discontinuation to understand the optimal discontinuation rate

Retrograde semaphorin-plexin signalling drives homeostatic synaptic plasticity.

Homeostatic signalling systems ensure stable but flexible neural activity and animal behaviour. Presynaptic homeostatic plasticity is a conserved form of neuronal homeostatic signalling that is observed in organisms ranging from Drosophila to human. Defining the underlying molecular mechanisms of neuronal homeostatic signalling will be essential in order to establish clear connections to the causes and progression of neurological disease. During neural development, semaphorin-plexin signalling instructs axon guidance and neuronal morphogenesis. However, semaphorins and plexins are also expressed in the adult brain. Here we show that semaphorin 2b (Sema2b) is a target-derived signal that acts upon presynaptic plexin B (PlexB) receptors to mediate the retrograde, homeostatic control of presynaptic neurotransmitter release at the neuromuscular junction in Drosophila. Further, we show that Sema2b-PlexB signalling regulates presynaptic homeostatic plasticity through the cytoplasmic protein Mical and the oxoreductase-dependent control of presynaptic actin. We propose that semaphorin-plexin signalling is an essential platform for the stabilization of synaptic transmission throughout the developing and mature nervous system. These findings may be relevant to the aetiology and treatment of diverse neurological and psychiatric diseases that are characterized by altered or inappropriate neural function and behaviour

The Formation of Low-Mass Transient X-Ray Binaries

We consider constraints on the formation of low-mass X-ray binaries containing neutron stars (NLMXBs) arising from the presence of soft X-ray transients among these systems. We show that in short-period systems driven by angular momentum loss these constraints require the secondary at the beginning of mass transfer to have a mass > 1.2 M_sun, and to be significantly nuclear-evolved. As a consequence a comparatively large fraction of such systems appear as soft X-ray transients even at short periods, as observed. Moreover the large initial secondary masses account for the rarity of NLMXBs at periods less than 3 hr. In contrast, NLMXB populations forming with large kick velocities would not have these properties, suggesting that the kick velocity is generally small compared to the pre-SN orbital velocity in a large fraction of systems. We derive constraints on progenitor system parameters and on the strength of magnetic braking.Comment: Accepted for publication in ApJ, 19 pages, 4 figure

Supernova Kicks, Magnetic Braking, and Neutron-Star Binaries

We consider the formation of low-mass X-ray binaries containing accreting neutron stars via the helium-star supernova channel. The predicted relative number of short-period transients provides a sensitive test of the input physics in this process. We investigate the effect of varying mean kick velocities, orbital angular momentum loss efficiencies, and common envelope ejection efficiencies on the subpopulation of short-period systems, both transient and persistent. Guided by the thermal-viscous disk instability model in irradiation-dominated disks, we posit that short-period transients have donors close to the end of core-hydrogen burning. We find that with increasing mean kick velocity the overall short-period fraction, s, grows, while the fraction, r, of systems with evolved donors among short-period systems drops. This effect, acting in opposite directions on these two fractions, allows us to constrain models of LMXB formation through comparison with observational estimates of s and r. Without fine tuning or extreme assumptions about evolutionary parameters, consistency between models and current observations is achieved for a regime of intermediate average kick magnitudes of about 100-200 km/s, provided that (i) orbital braking for systems with donor masses in the range 1-1.5 solar masses is weak, i.e., much less effective than a simple extrapolation of standard magnetic braking beyond 1.0 solar mass would suggest, and (ii) the efficiency of common envelope ejection is low.Comment: 24 pages, AAATeX, accepted for publication in The Astrophysical Journa

Antiseizure medication withdrawal risk estimation and recommendations: A survey of American Academy of Neurology and EpiCARE members

Objective Choosing candidates for antiseizure medication (ASM) withdrawal in well‐controlled epilepsy is challenging. We evaluated (a) the correlation between neurologists' seizure risk estimation (“clinician predictions”) vs calculated predictions, (b) how viewing calculated predictions influenced recommendations, and (c) barriers to using risk calculation.MethodsWe asked US and European neurologists to predict 2‐year seizure risk after ASM withdrawal for hypothetical vignettes. We compared ASM withdrawal recommendations before vs after viewing calculated predictions, using generalized linear models. Results Three‐hundred and forty‐six neurologists responded. There was moderate correlation between clinician and calculated predictions (Spearman coefficient 0.42). Clinician predictions varied widely, for example, predictions ranged 5%‐100% for a 2‐year seizure‐free adult without epileptiform abnormalities. Mean clinician predictions exceeded calculated predictions for vignettes with epileptiform abnormalities (eg, childhood absence epilepsy: clinician 65%, 95% confidence interval [CI] 57%‐74%; calculated 46%) and surgical vignettes (eg, focal cortical dysplasia 6‐month seizure‐free mean clinician 56%, 95% CI 52%‐60%; calculated 28%). Clinicians overestimated the influence of epileptiform EEG findings on withdrawal risk (26%, 95% CI 24%‐28%) compared with calculators (14%, 95% 13%‐14%). Viewing calculated predictions slightly reduced willingness to withdraw (−0.8/10 change, 95% CI −1.0 to −0.7), particularly for vignettes without epileptiform abnormalities. The greatest barrier to calculator use was doubting its accuracy (44%). Significance Clinicians overestimated the influence of abnormal EEGs particularly for low‐risk patients and overestimated risk and the influence of seizure‐free duration for surgical patients, compared with calculators. These data may question widespread ordering of EEGs or time‐based seizure‐free thresholds for surgical patients. Viewing calculated predictions reduced willingness to withdraw particularly without epileptiform abnormalities

Lysosomes in iron metabolism, ageing and apoptosis

The lysosomal compartment is essential for a variety of cellular functions, including the normal turnover of most long-lived proteins and all organelles. The compartment consists of numerous acidic vesicles (pH ∼4 to 5) that constantly fuse and divide. It receives a large number of hydrolases (∼50) from the trans-Golgi network, and substrates from both the cells’ outside (heterophagy) and inside (autophagy). Many macromolecules contain iron that gives rise to an iron-rich environment in lysosomes that recently have degraded such macromolecules. Iron-rich lysosomes are sensitive to oxidative stress, while ‘resting’ lysosomes, which have not recently participated in autophagic events, are not. The magnitude of oxidative stress determines the degree of lysosomal destabilization and, consequently, whether arrested growth, reparative autophagy, apoptosis, or necrosis will follow. Heterophagy is the first step in the process by which immunocompetent cells modify antigens and produce antibodies, while exocytosis of lysosomal enzymes may promote tumor invasion, angiogenesis, and metastasis. Apart from being an essential turnover process, autophagy is also a mechanism by which cells will be able to sustain temporary starvation and rid themselves of intracellular organisms that have invaded, although some pathogens have evolved mechanisms to prevent their destruction. Mutated lysosomal enzymes are the underlying cause of a number of lysosomal storage diseases involving the accumulation of materials that would be the substrate for the corresponding hydrolases, were they not defective. The normal, low-level diffusion of hydrogen peroxide into iron-rich lysosomes causes the slow formation of lipofuscin in long-lived postmitotic cells, where it occupies a substantial part of the lysosomal compartment at the end of the life span. This seems to result in the diversion of newly produced lysosomal enzymes away from autophagosomes, leading to the accumulation of malfunctioning mitochondria and proteins with consequent cellular dysfunction. If autophagy were a perfect turnover process, postmitotic ageing and several age-related neurodegenerative diseases would, perhaps, not take place