Harnessing the carrier wave of light as an alternating-current bias may enable electronics at optical clock rates
. Lightwave-driven currents have been assumed to be essential for high-harmonic ...generation in solids
, charge transport in nanostructures
, attosecond-streaking experiments
and atomic-resolution ultrafast microscopy
. However, in conventional semiconductors and dielectrics, the finite effective mass and ultrafast scattering of electrons limit their ballistic excursion and velocity. The Dirac-like, quasi-relativistic band structure of topological insulators
may allow these constraints to be lifted and may thus open a new era of lightwave electronics. To understand the associated, complex motion of electrons, comprehensive experimental access to carrier-wave-driven currents is crucial. Here we report angle-resolved photoemission spectroscopy with subcycle time resolution that enables us to observe directly how the carrier wave of a terahertz light pulse accelerates Dirac fermions in the band structure of the topological surface state of Bi
Te
. While terahertz streaking of photoemitted electrons traces the electromagnetic field at the surface, the acceleration of Dirac states leads to a strong redistribution of electrons in momentum space. The inertia-free surface currents are protected by spin-momentum locking and reach peak densities as large as two amps per centimetre, with ballistic mean free paths of several hundreds of nanometres, opening up a realistic parameter space for all-coherent lightwave-driven electronic devices. Furthermore, our subcycle-resolution analysis of the band structure may greatly improve our understanding of electron dynamics and strong-field interaction in solids.
This study presents investigations on the additive manufacturing of hot work steel with the energy-reduced gas metal arc welding (GMAW) process, which is a cold metal transfer (CMT) process. The ...paper analyses the influence of arc energy and the thermal field on the resulting mechanical properties and microstructure of the material. The investigations were carried out with hot work tool steel X37CrMoV 5-1, which is used for the manufacturing of plastic moulds, hot extrusion dies, and forging dies. The results show that this steel can be used to generate 3D metal components or structures with high reproducibility, near-net-shaped geometry, absence of cracks, and a deposition rate of up to 3.6 kg/h. The variation of the wire feed speed and the welding speed enables the production of weld beads of width up to 9.4 mm. The mechanical properties of the generated structures can be adapted by the dominant thermal field, which in turn is influenced by the bypass temperature and the electric arc energy. A determining factor to describe the main variables of the welding process is represented by energy per unit length EL. If the bypass temperature is above the martensite start temperature (Ms), there is a homogeneous hardness level along the height of the additively manufactured structure height as long as the energy produced by the welding arc is enough to keep the temperature of all layers above Ms.
Strong light fields have created opportunities to tailor novel functionalities of solids
. Floquet-Bloch states can form under periodic driving of electrons and enable exotic quantum phases
. On ...subcycle timescales, lightwaves can simultaneously drive intraband currents
and interband transitions
, which enable high-harmonic generation
and pave the way towards ultrafast electronics. Yet, the interplay of intraband and interband excitations and their relation to Floquet physics have been key open questions as dynamical aspects of Floquet states have remained elusive. Here we provide this link by visualizing the ultrafast build-up of Floquet-Bloch bands with time-resolved and angle-resolved photoemission spectroscopy. We drive surface states on a topological insulator
with mid-infrared fields-strong enough for high-harmonic generation-and directly monitor the transient band structure with subcycle time resolution. Starting with strong intraband currents, we observe how Floquet sidebands emerge within a single optical cycle; intraband acceleration simultaneously proceeds in multiple sidebands until high-energy electrons scatter into bulk states and dissipation destroys the Floquet bands. Quantum non-equilibrium calculations explain the simultaneous occurrence of Floquet states with intraband and interband dynamics. Our joint experiment and theory study provides a direct time-domain view of Floquet physics and explores the fundamental frontiers of ultrafast band-structure engineering.
Objective
The histopathological features of malignant hyperthermia (MH) and non-anaesthetic (mostly exertional) rhabdomyolysis (RM) due to
RYR1
mutations have only been reported in a few cases.
...Methods
We performed a retrospective multi-centre cohort study focussing on the histopathological features of patients with MH or RM due to
RYR1
mutations (1987–2017). All muscle biopsies were reviewed by a neuromuscular pathologist. Additional morphometric and electron microscopic analysis were performed where possible.
Results
Through the six participating centres we identified 50 patients from 46 families, including patients with MH (
n
= 31) and RM (
n
= 19). Overall, the biopsy of 90% of patients showed one or more myopathic features including: increased fibre size variability (
n
= 44), increase in the number of fibres with internal nuclei (
n
= 30), and type I fibre predominance (
n
= 13). Abnormalities on oxidative staining, generally considered to be more specifically associated with
RYR1
-related congenital myopathies, were observed in 52%, and included unevenness (
n
= 24), central cores (
n
= 7) and multi-minicores (
n
= 3). Apart from oxidative staining abnormalities more frequently observed in MH patients, the histopathological spectrum was similar between the two groups. There was no correlation between the presence of cores and the occurrence of clinically detectable weakness or presence of (likely) pathogenic variants.
Conclusions
Patients with
RYR1
-related MH and RM exhibit a similar histopathological spectrum, ranging from mild myopathic changes to cores and other features typical of
RYR1
-related congenital myopathies. Suggestive histopathological features may support
RYR1
involvement, also in cases where the in vitro contracture test is not informative.
We study ultrafast population dynamics in the topological surface state of SbFormula: see textTeFormula: see text in two-dimensional momentum space with time- and angle-resolved two-photon ...photoemission spectroscopy. Linearly polarized mid-infrared pump pulses are used to permit a direct optical excitation across the Dirac point. We show that this resonant excitation is strongly enhanced within the Dirac cone along three of the six Formula: see text-Formula: see text directions and results in a macroscopic photocurrent when the plane of incidence is aligned along a Formula: see text-Formula: see text direction. Our experimental approach makes it possible to disentangle the decay of transiently excited population and photocurent by elastic and inelastic electron scattering within the full Dirac cone in unprecedented detail. This is utilized to show that doping of SbFormula: see textTeFormula: see text by vanadium atoms strongly enhances inelastic electron scattering to lower energies, but only scarcely affects elastic scattering around the Dirac cone.
Quantum anomalous Hall effect (QAHE) is a key phenomenon for low power-consumption device applications owing to its dissipationless spin-polarized and quantized current in the absence of an external ...magnetic field. However, the recorded working temperature of the QAHE is still very low. Here we systematically investigate the magnetic dopants induced modifications from the view points of magnetic, structural and electronic properties and the ultrafast carrier dynamics in a series of V-doped Sb2Te3 samples of composition Sb2−xVxTe3 with x = 0, 0.015 and 0.03. Element specific x-ray magnetic circular dichroism signifies that the ferromagnetism of V-doped Sb2Te3 is governed by the p-d hybridization between the host carrier and the magnetic dopant. Time- and angle-resolved photoemission spectroscopy excited with mid-infrared pulses has revealed that the V impurity induced states underlying the topological surface state (TSS) add scattering channels that significantly shorten the duration of transient surface electrons down to the 100 fs scale. This is in a sharp contrast to the prolonged duration reported for pristine samples though the TSS is located inside the bulk energy gap of the host in either magnetic or non-magnetic cases. It implies the presence of a mobility gap in the bulk energy gap region of the host material that would work toward the robust QAHE. Our findings shed light on the material design for low-energy-consuming device applications.
To investigate the maximum tolerated dose of ranibizumab administered as a single intravitreal injection.
Open-label, 5-center, uncontrolled, prospective, dose-ranging, interventional case series.
...Twenty-seven patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) with best-corrected Snellen equivalent visual acuity (VA) of 20/100 or worse and considered ineligible for laser photocoagulation or photodynamic therapy.
A single intravitreal injection of ranibizumab was to be administered at 1 of 6 escalating doses (50, 150, 300, 500, 1000, and 2000 microg), with escalation to the next dose level occurring only after the safety and tolerability of the lower dose level was established through postinjection day 14. Follow-up examinations were performed on postinjection days 1, 3, 7, 14, 42, and 90. Enrollment was stopped if > or =2 patients experienced dose-limiting toxicity.
The primary safety measures were changes from baseline in VA, intraocular pressure (IOP), intraocular inflammation, and production of antiranibizumab antibody. Dose-limiting toxicity was defined by intraocular inflammation, elevated IOP, reduced VA, or hemorrhage within 90 days after injection.
All patients completed this single intravitreal injection study, and 500 microg of ranibizumab was the maximum tolerated dose. At the higher dose of 1000 microg, significant intraocular inflammation was noted. All adverse events were self-limited, and no infectious endophthalmitis occurred. Aqueous or vitreous ocular inflammation occurred in 12 subjects, with complete resolution within 42 days. In 9 of the subjects, the inflammation was graded as trace to 1+ and required no treatment; in 3 of the subjects, the inflammation was graded as 2+ or 3+, and 2 of the 3 were treated with topical 1% prednisolone acetate. No serum antiranibizumab antibodies were detected. All patients had VA similar or improved compared with baseline values.
The maximum tolerated single dose of ranibizumab in neovascular AMD patients was 500 microg. Single intravitreal injections of ranibizumab up to a dose of 500 microg were safe and well tolerated in this small group of patients.
Background
A variant in the canine phosphodiesterase (PDE) 5A gene (PDE5A:E90K) is associated with decreased concentrations of circulating cyclic guanosine monophosphate (cGMP) and response to PDE5 ...inhibitor treatment. Pimobendan is a PDE inhibitor recommended for medical treatment of certain stages of myxomatous mitral valve disease (MMVD) in dogs.
Hypothesis
PDE5A:E90K polymorphism attenuates the inhibitory effect of pimobendan on in vitro platelet aggregation and increases basal platelet aggregation in Cavalier King Charles Spaniels (CKCS). Selected clinical variables (MMVD severity, sex, age, hematocrit, platelet count in platelet‐rich plasma PRP, and echocardiographic left ventricular fractional shortening LV FS) will not show an association with results.
Animals
Fifty‐two privately owned CKCS with no or preclinical MMVD.
Methods
Using blood samples, we prospectively assessed PDE5A genotype using Sanger sequencing and adenosine diphosphate‐induced platelet aggregation response (area under the curve AUC, maximal aggregation MaxA, and velocity Vel) with and without pimobendan using light transmission aggregometry. Dogs also underwent echocardiography.
Results
Pimobendan inhibited platelet function as measured by AUC, MaxA, and Vel at a concentration of 10 μM (P < .0001) and Vel at 0.03 μM (P < .001). PDE5A:E90K polymorphism did not influence the inhibitory effect of pimobendan or basal platelet aggregation response.
Conclusions and Clinical Importance
The PDE5A:E90K polymorphism did not influence in vitro basal platelet aggregation response or the inhibitory effect of pimobendan on platelet aggregation in CKCS. Dogs with the PDE5A:E90K polymorphism did not appear to have altered platelet function or response to pimobendan treatment.
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