Imaging stress and magnetism at high pressures using a nanoscale quantum sensor.

Pressure alters the physical, chemical, and electronic properties of matter. The diamond anvil cell enables tabletop experiments to investigate a diverse landscape of high-pressure phenomena. Here, we introduce and use a nanoscale sensing platform that integrates nitrogen-vacancy (NV) color centers directly into the culet of diamond anvils. We demonstrate the versatility of this platform by performing diffraction-limited imaging of both stress fields and magnetism as a function of pressure and temperature. We quantify all normal and shear stress components and demonstrate vector magnetic field imaging, enabling measurement of the pressure-driven [Formula: see text] phase transition in iron and the complex pressure-temperature phase diagram of gadolinium. A complementary NV-sensing modality using noise spectroscopy enables the characterization of phase transitions even in the absence of static magnetic signatures.

Spin-orbit-driven band inversion in bilayer graphene by the van der Waals proximity effect.

Spin-orbit coupling (SOC) is the key to realizing time-reversal-invariant topological phases of matter1,2. SOC was predicted by Kane and Mele3 to stabilize a quantum spin Hall insulator; however, the weak intrinsic SOC in monolayer graphene4-7 has precluded experimental observation in this material. Here we exploit a layer-selective proximity effect-achieved via a van der Waals contact with a semiconducting transition-metal dichalcogenide8-21-to engineer Kane-Mele SOC in ultra clean bilayer graphene. Using high-resolution capacitance measurements to probe the bulk electronic compressibility, we find that SOC leads to the formation of a distinct, incompressible, gapped phase at charge neutrality. The experimental data agree quantitatively with a simple theoretical model in which the new phase results from SOC-driven band inversion. In contrast to Kane-Mele SOC in monolayer graphene, the inverted phase is not expected to be a time-reversal-invariant topological insulator, despite being separated from conventional band insulators by electric-field-tuned phase transitions where crystal symmetry mandates that the bulk gap must close22. Our electrical transport measurements reveal that the inverted phase has a conductivity of approximately e2/h (where e is the electron charge and h Planck's constant), which is suppressed by exceptionally small in-plane magnetic fields. The high conductivity and anomalous magnetoresistance are consistent with theoretical models that predict helical edge states within the inverted phase that are protected from backscattering by an emergent spin symmetry that remains robust even for large Rashba SOC. Our results pave the way for proximity engineering of strong topological insulators as well as correlated quantum phases in the strong spin-orbit regime in graphene heterostructures.

Direct measurement of discrete valley and orbital quantum numbers in bilayer graphene.

The high magnetic field electronic structure of bilayer graphene is enhanced by the spin, valley isospin, and an accidental orbital degeneracy, leading to a complex phase diagram of broken symmetry states. Here, we present a technique for measuring the layer-resolved charge density, from which we directly determine the valley and orbital polarization within the zero energy Landau level. Layer polarization evolves in discrete steps across 32 electric field-tuned phase transitions between states of different valley, spin, and orbital order, including previously unobserved orbitally polarized states stabilized by skew interlayer hopping. We fit our data to a model that captures both single-particle and interaction-induced anisotropies, providing a complete picture of this correlated electron system. The resulting roadmap to symmetry breaking paves the way for deterministic engineering of fractional quantum Hall states, while our layer-resolved technique is readily extendable to other two-dimensional materials where layer polarization maps to the valley or spin quantum numbers.The phase diagram of bilayer graphene at high magnetic fields has been an outstanding question, with orders possibly between multiple internal quantum degrees of freedom. Here, Hunt et al. report the measurement of the valley and orbital order, allowing them to directly reconstruct the phase diagram.

Tunable interacting composite fermion phases in a half-filled bilayer-graphene Landau level.

Non-Abelian anyons are a type of quasiparticle with the potential to encode quantum information in topological qubits protected from decoherence. Experimental systems that are predicted to harbour non-Abelian anyons include p-wave superfluids, superconducting systems with strong spin-orbit coupling, and paired states of interacting composite fermions that emerge at even denominators in the fractional quantum Hall (FQH) regime. Although even-denominator FQH states have been observed in several two-dimensional systems, small energy gaps and limited tunability have stymied definitive experimental probes of their non-Abelian nature. Here we report the observation of robust even-denominator FQH phases at half-integer Landau-level filling in van der Waals heterostructures consisting of dual-gated, hexagonal-boron-nitride-encapsulated bilayer graphene. The measured energy gap is three times larger than observed previously. We compare these FQH phases with numerical and theoretical models while simultaneously controlling the carrier density, layer polarization and magnetic field, and find evidence for the paired Pfaffian phase that is predicted to host non-Abelian anyons. Electric-field-controlled level crossings between states with different Landau-level indices reveal a cascade of FQH phase transitions, including a continuous phase transition between the even-denominator FQH state and a compressible composite fermion liquid. Our results establish graphene as a pristine and tunable experimental platform for studying the interplay between topology and quantum criticality, and for detecting non-Abelian qubits.

Cerebrovascular reactivity to l-arginine in the anterior and posterior cerebral circulation in migraine patients.

OBJECTIVE - Cerebral infarction preferentially affects the posterior cerebral artery distribution in migraine patients. The results obtained from the few known studies that have compared the anterior and posterior cerebral endothelial function are contradictory. To the best of our knowledge, cerebrovascular reactivity to L-arginine (CVR), measured by transcranial Doppler sonography (TCD), has not been previously used to determine the posterior cerebral endothelial function in migraine patients with (MwA) and without aura (MwoA). MATERIALS AND METHODS - Forty migraine patients without comorbidities (20 MwA, 20 MwoA) and 20 healthy subjects were included. By employing strict inclusion criteria, we avoided the possible vascular risk factors. Mean arterial velocity in the middle cerebral artery (MCA) and the posterior cerebral artery (PCA) was measured by TCD before and after infusion of L-arginine, and CVR to L-arginine was then calculated. RESULTS - All migraine patients had lower CVR to L-arginine in PCA (P = 0.002) and similar in MCA (P = 0.29) compared to healthy subjects. This difference was also present in MwA and MwoA compared to healthy subjects (P = 0.003). CONCLUSIONS - Lower CVR to L-arginine in PCA in migraine patients could associate migraine and cerebral infarcts that are more common in the posterior cerebral artery distribution.

Isolated bulbar paralysis in a patient with medullar tau pathology: a case report.

Increased morbidity and mortality rates as well as some other manifestations in Alzheimer's disease can be explained by subcortical degeneration. Pathological evidence is scarce but confirmative. We report a 77-year-old patient who presented with a 6-year history of dyspnoea, stridor and dysphagia. Unexpectedly, histopathological examination disclosed extensive degeneration of the medulla by tau pathology. The majority of symptoms and signs could be explained by the medullary tau pathology. Whether the medullary tau pathology in this case was a rare aberrant progression of Alzheimer's disease or a new presentation of tauopathy concomitant with subclinical Alzheimer's disease should be elucidated by additional studies.

Autonomic dysfunction in presymptomatic and early symptomatic Huntington's disease.

OBJECTIVES: Although autonomic dysfunction was found in advanced Huntington's disease (HD) patients it is not clear whether there is autonomic dysfunction in presymptomatic and early symptomatic HD. MATERIAL & METHODS: Different cardiovascular autonomic tests were performed in 14 presymptomatic HD mutation carriers (PHD), 11 early symptomatic HD patients (EHD) and in 25 sex and age matched controls. RESULTS: We found attenuated response to simple mental arithmetic test (relative heart rate in PHD and EHD was 10% lower than in controls; diastolic pressure was 10.6% lower in EHD than in controls; P < 0.05) and exaggerated response to the late phase of cold pressor test (relative heart rate was 10% higher in PHD and 7% higher in EHD than in controls; P < 0.05). The rest of the cardiovascular autonomic tests did not reveal significant differences between patients and controls. CONCLUSIONS: Our results suggest that subtle autonomic dysfunction occurs even in PHD and EHD.

Flow-mediated dilatation and intima-media thickness in patients with lacunar infarctions.

OBJECTIVES: To evaluate systemic endothelial function and atherosclerotic changes in patients with lacunar infarctions (LI) we examined flow-mediated dilatation (FMD) and intima-media thickness (IMT) and compared them to patients with similar risk factors (SR) and healthy controls. METHODS: FMD and IMT were investigated in patients with LI (20 patients, aged 60.9 +/- 7.3 years), 21 age- and gender-matched patients with SR and 21 healthy controls. RESULTS: FMD was more impaired in patients with LI (0.4% +/- 5.0%) compared to patients with SR (3.8% +/- 4.8%) and healthy controls (7.9% +/- 6.0%) (P < or = 0.01), whereas IMT was similarly thickened in both groups of patients. CONCLUSIONS: We found that patients with LI have a diminished FMD, but a similar IMT, compared to patients with SR. Our results reveal that for a given level of atherosclerosis patients with LI have additional endothelial impairment.

Effect of generalized sympathetic activation by cold pressor test on cerebral hemodynamics in diabetics with autonomic dysfunction.

BACKGROUND: We examined the effects of the cold pressor test on the cerebral circulation in diabetics with autonomic dysfunction without orthostatic hypotension using transcranial Doppler. METHODS: Twenty diabetics with autonomic dysfunction and 19 age-matched healthy controls participated in the study. The mean arterial blood velocity was measured in the middle cerebral artery during the cold pressor test together with the mean arterial blood pressure. RESULTS: The mean arterial blood velocity significantly (p < 0.01) increased during the 1st, 2nd, and 3rd min of the cold pressor test by 10.6, 14.1, and 13.4%, respectively, in the control subjects and by 5.8, 7.2, and 6.8%, respectively, in the diabetics. Simultaneously, the mean arterial blood pressure significantly (p < 0.01) increased by 12, 26, and 23%, respectively, in the controls and by 9.4, 12.4 and 12.9%, respectively, in the diabetics. The increases in the mean arterial velocity as well as in the mean arterial blood pressure were significantly higher in the controls than in the diabetics (p < 0.01). The change in the mean arterial blood pressure related significantly to the change in the mean arterial blood velocity both in the controls (p < 0.01, r = 0.76) and in the diabetics (p < 0.01; r = 0.59). The slope of the regression line was significantly steeper in the controls (b = 0.42, SE = 0.05) as compared with the diabetics with autonomic dysfunction (b = 0.27, SE = 0.05; p = 0.02). Moreover, also the relative increase in the cerebrovascular resistance index was higher in the controls than in the diabetics (p < 0.05). CONCLUSION: These findings in the diabetics with autonomic neuropathy, but without orthostatic hypotension, suggest a failure in the cerebral autoregulation due to impaired cerebrovascular neurogenic control.

Coupling between visual evoked cerebral blood flow velocity responses and visual evoked potentials in migraneurs.

Neurovascular coupling may be altered in migraneurs. Therefore, visual evoked potentials (VEP) and visually evoked cerebral blood flow velocity responses (VEFR) were simultaneously recorded in 30 healthy controls and 30 migraneurs interictally using a checkerboard stimulus with visual contrasts of 1%, 10% and 100%. The VEFR were measured in the posterior cerebral artery using transcranial Doppler and VEP were recorded from occipital leads. We found an increase in VEFR and VEP in both the healthy and migraneur groups (P < 0.01). VEFR were significantly higher in migraneurs (P < 0.01), while VEP did not significantly differ between the groups (P > 0.05). Regression showed a significant association between VEP and VEFR in both healthy controls (r = 0.66, P < 0.01) and migraneurs (r = 0.63, P < 0.01). The regression coefficient of migraneurs (b = 0.88, SE = 0.08) was significantly higher than that of healthy controls (b = 0.55, SE = 0.07) (P = 0.04). We conclude that neurovascular coupling is increased in migraneurs interictally.

Testing of cerebral endothelium function with L-arginine after stroke.

BACKGROUND: Endothelium-dependent vasodilatation could be impaired during hypoperfusion. L-arginine (L-A), a precursor of nitric oxide, is able to elicit endothelium-dependent vasodilatation. To determine cerebral vascular endothelial function in the early stages after ischemic stroke, we studied cerebrovascular reactivity to L-A with transcranial Doppler (TCD). METHODS: The study group consisted of 15 patients with the middle cerebral artery syndrome, aged 57.6+/-9.8 years. They were investigated on days 7 to 10 after ischemic stroke. The control group consisted of 15 healthy volunteers, aged 58+/-10.7 years. All subjects received an intravenous infusion of L-A over 20 min at a rate of 1.5 g/min. The mean arterial velocity (vm) was measured in both middle cerebral arteries by using a bitemporal monitoring system (Multi-Dop X4, DWL). At the same time, the mean arterial pressure (MAP) and heart rate (HR) were measured by Finapres and ECG. The end-tidal CO2 (Et-Co2) was monitored by capnograph. The Vm over 5-min intervals at rest and during the infusion of L-A was determined by using the DWL TCD8 software. RESULTS: The Vm significantly increased in both hemispheres of both groups (p=0.00). Vm differences between rest and L-A stimulation were lower in the ischemic hemispheres compared to the healthy ones (p=0.00), but did not differ between the ischemic hemispheres and hemispheres of the healthy group (p>0.05). MAP, HR and Et-Co2 did not change during the infusion (p>0.05). CONCLUSIONS: Cerebrovascular reactivity to L-A is impaired in patients with recent stroke. The amino acid could thus be useful in testing endothelium function both in healthy persons and in stroke patients since endothelium dysfunction seems to be an important factor in reperfusion injury.

The effect of age on cerebrovascular reactivity to cold pressor test and head-up tilt.

OBJECTIVE: To compare the cold pressor test (CPT) and head-up tilt (HUT) responses of the older and younger healthy individuals by transcranial Doppler. SUBJECTS AND METHODS: Forty healthy volunteers were divided into two age groups (18-39 years, 40-69 years). Mean blood velocity (v(m)) in both middle cerebral arteries was monitored during CPT and HUT. Mean arterial blood pressure, heart rate and end-tidal CO(2) (Et-CO(2)) were measured simultaneously. RESULTS: The v(m) increased by 7.1% during CPT and decreased by 10.1% during HUT. The v(m) responses were significantly lower in the older group (P < 0.01). Linear regression analysis showed a significant effect of age on dv(m) during both CPT (P < 0.01) as well as HUT (P < 0.01). CONCLUSION: The age affected the v(m) responses to CPT and HUT in the group of older subjects.

Influence of the cold pressor test on the middle cerebral artery circulation.

Cold pressor test (CPT) evokes generalized activation of the sympathetic nervous system (SNS). The activity of SNS may be estimated by monitoring the mean blood velocity (v(m)) in the middle cerebral artery (MCA) by using a transcranial Doppler monitoring system (TCD). To determine the response of SNS, we studied the v(m) during CPT. Thirty-four healthy volunteers, 13 female and 21 male (mean age 34 +/- 9.5 years, range 18 to 55 years) participated in our study. The experiment consisted of a 5-min baseline period followed by a 3-min immersion of the right hand in ice water. Blood velocity in both MCA's was monitored by bitemporal 2 MHz probes by using a Multi-Dop X4. MAP and heart rate (HR) were measured simultaneously by a Finapres non-invasive blood pressure monitor and a computerized ECG system. End-tidal CO2 (Et-CO2) was measured with an infrared capnograph. To determine v(m) over a chosen time interval the TCD-8 software was utilized. The results showed that during CPT v(m), MAP, and HR increased significantly (P < 0.01) for 9.8%, 18.5%, and 3.6%, respectively. Et-CO2 did not change significantly (P > 0.05). The increase of v(m) was also significantly higher in the stimulated hemispheres (P = 0.005) regarding to unstimulated ones. The increase of v(m) during CPT was not gender dependent. To establish the association between variables the models of multivariate regression were used. Multiple regression CPT model was significant (P < 0.01) and fitted data moderately well (R2 = 0.28). MAP and Et-CO2 were significant in the model (P < 0.01). It seems that the reactivity of the SNS can be estimated by measuring v(m) with TCD during CPT.