Energy-Constrained Discrimination of Unitaries, Quantum Speed Limits, and a Gaussian Solovay-Kitaev Theorem.

We investigate the energy-constrained (EC) diamond norm distance between unitary channels acting on possibly infinite-dimensional quantum systems, and establish a number of results. First, we prove that optimal EC discrimination between two unitary channels does not require the use of any entanglement. Extending a result by Acín, we also show that a finite number of parallel queries suffices to achieve zero error discrimination even in this EC setting. Second, we employ EC diamond norms to study a novel type of quantum speed limits, which apply to pairs of quantum dynamical semigroups. We expect these results to be relevant for benchmarking internal dynamics of quantum devices. Third, we establish a version of the Solovay-Kitaev theorem that applies to the group of Gaussian unitaries over a finite number of modes, with the approximation error being measured with respect to the EC diamond norm relative to the photon number Hamiltonian.

Convergence Rates for the Quantum Central Limit Theorem.

Various quantum analogues of the central limit theorem, which is one of the cornerstones of probability theory, are known in the literature. One such analogue, due to Cushen and Hudson, is of particular relevance for quantum optics. It implies that the state in any single output arm of an n-splitter, which is fed with n copies of a centred state ρ with finite second moments, converges to the Gaussian state with the same first and second moments as ρ . Here we exploit the phase space formalism to carry out a refined analysis of the rate of convergence in this quantum central limit theorem. For instance, we prove that the convergence takes place at a rate O n - 1 / 2 in the Hilbert-Schmidt norm whenever the third moments of ρ are finite. Trace norm or relative entropy bounds can be obtained by leveraging the energy boundedness of the state. Via analytical and numerical examples we show that our results are tight in many respects. An extension of our proof techniques to the non-i.i.d. setting is used to analyse a new model of a lossy optical fibre, where a given m-mode state enters a cascade of n beam splitters of equal transmissivities λ 1 / n fed with an arbitrary (but fixed) environment state. Assuming that the latter has finite third moments, and ignoring unitaries, we show that the effective channel converges in diamond norm to a simple thermal attenuator, with a rate O ( n - 1 2 ( m + 1 ) ) . This allows us to establish bounds on the classical and quantum capacities of the cascade channel. Along the way, we derive several results that may be of independent interest. For example, we prove that any quantum characteristic function χ ρ is uniformly bounded by some η ρ < 1 outside of any neighbourhood of the origin; also, η ρ can be made to depend only on the energy of the state ρ .

Geometry of Energy Landscapes and the Optimizability of Deep Neural Networks.

Deep neural networks are workhorse models in machine learning with multiple layers of nonlinear functions composed in series. Their loss function is highly nonconvex, yet empirically even gradient descent minimization is sufficient to arrive at accurate and predictive models. It is hitherto unknown why deep neural networks are easily optimizable. We analyze the energy landscape of a spin glass model of deep neural networks using random matrix theory and algebraic geometry. We analytically show that the multilayered structure holds the key to optimizability: Fixing the number of parameters and increasing network depth, the number of stationary points in the loss function decreases, minima become more clustered in parameter space, and the trade-off between the depth and width of minima becomes less severe. Our analytical results are numerically verified through comparison with neural networks trained on a set of classical benchmark datasets. Our model uncovers generic design principles of machine learning models.

Binding of HasA by its transmembrane receptor HasR follows a conformational funnel mechanism.

HasR in the outer membrane of Serratia marcescens binds secreted, heme-loaded HasA and translocates the heme to the periplasm to satisfy the cell's demand for iron. The previously published crystal structure of the wild-type complex showed HasA in a very specific binding arrangement with HasR, apt to relax the grasp on the heme and assure its directed transfer to the HasR-binding site. Here, we present a new crystal structure of the heme-loaded HasA arranged with a mutant of HasR, called double mutant (DM) in the following that seemed to mimic a precursor stage of the abovementioned final arrangement before heme transfer. To test this, we performed first molecular dynamics (MD) simulations starting at the crystal structure of the complex of HasA with the DM mutant and then targeted MD simulations of the entire binding process beginning with heme-loaded HasA in solution. When the simulation starts with the former complex, the two proteins in most simulations do not dissociate. When the mutations are reverted to the wild-type sequence, dissociation and development toward the wild-type complex occur in most simulations. This indicates that the mutations create or enhance a local energy minimum. In the targeted MD simulations, the first protein contacts depend upon the chosen starting position of HasA in solution. Subsequently, heme-loaded HasA slides on the external surface of HasR on paths that converge toward the specific arrangement apt for heme transfer. The targeted simulations end when HasR starts to relax the grasp on the heme, the subsequent events being in a time regime inaccessible to the available computing power. Interestingly, none of the ten independent simulation paths visits exactly the arrangement of HasA with HasR seen in the crystal structure of the mutant. Two factors which do not exclude each other could explain these observations: the double mutation creates a non-physiologic potential energy minimum between the two proteins and /or the target potential in the simulation pushes the system along paths deviating from the low-energy paths of the native binding processes. Our results support the former view, but do not exclude the latter possibility.

Probing plasmonic excitation mechanisms and far-field radiation of single-crystalline gold tapers with electrons.

Conical metallic tapers represent an intriguing subclass of metallic nanostructures, as their plasmonic properties show interesting characteristics in strong correlation to their geometrical properties. This is important for possible applications such as in the field of scanning optical microscopy, as favourable plasmonic resonance behaviour can be tailored by optimizing structural parameters like surface roughness or opening angle. Here, we review our recent studies, where single-crystalline gold tapers were investigated experimentally by means of electron energy-loss and cathodoluminescence spectroscopy techniques inside electron microscopes, supported by theoretical finite-difference time-domain calculations. Through the study of tapers with various opening angles, the underlying resonance mechanisms are discussed. This article is part of a discussion meeting issue 'Dynamic in situ microscopy relating structure and function'.

Steering second-harmonic radiation through local excitations of plasmon.

We propose an approach of steering the second harmonic (SH) emission from a single plasmonic structure, through local excitations of plasmon. The proposed idea is confirmed experimentally, by adjusting the incident beam position at the fundamental frequency, on a single plasmonic antenna. A significant directivity change ( ± 52°) for the SH emission is observed with submicrometer adjustment ( ± 250 nm) of the excitation beam position, over broadband SH frequencies. Providing a simple method of controlling the directivity of frequency-converted light, our approach paves the way to new design strategy for nonlinear optical devices with various nonlinear wavefronts.

Cellular and acellular ex vivo lung perfusion preserve functional lung ultrastructure in a large animal model: a stereological study.

BACKGROUND: Ex vivo lung perfusion (EVLP) is used by an increasing number of transplant centres. It is still controversial whether an acellular or cellular (erythrocyte enriched) perfusate is preferable. The aim of this paper was to evaluate whether acellular (aEVLP) or cellular EVLP (cEVLP) preserves functional lung ultrastructure better and to generate a hypothesis regarding possible underlying mechanisms. METHODS: Lungs of 20 pigs were assigned to 4 groups: control, ischaemia (24 h), aEVLP and cEVLP (both EVLP groups: 24 h ischaemia + 12 h EVLP). After experimental procedures, whole lungs were perfusion fixed, samples for light and electron microscopic stereology were taken, and ventilation, diffusion and perfusion related parameters were estimated. RESULTS: Lung structure was well preserved in all groups. Lungs had less atelectasis and higher air content after EVLP. No significant group differences were found in alveolar septum composition or blood-air barrier thickness. Small amounts of intraalveolar oedema were detected in both EVLP groups but significantly more in aEVLP than in cEVLP. CONCLUSIONS: Both EVLP protocols supported lungs well for up to 12 h and could largely prevent ischaemia ex vivo reperfusion associated lung injury. In both EVLP groups, oedema volume remained below the level of functional relevance. The group difference in oedema formation was possibly due to inferior septal perfusion in aEVLP.

Suppression of Th1 differentiation by tryptophan supplementation in vivo.

Metabolism of the essential amino acid tryptophan (trp) is a key endogenous immunosuppressive pathway restricting inflammatory responses. Tryptophan metabolites promote regulatory T cell (Treg) differentiation and suppress proinflammatory T helper cell (Th)1 and Th17 phenotypes. It has been shown that treatment with natural and synthetic tryptophan metabolites can suppress autoimmune neuroinflammation in preclinical animal models. Here, we tested if oral intake of tryptophan would increase immunosuppressive tryptophan metabolites and ameliorate autoimmune neuroinflammation as a safe approach to treat autoimmune disorders like multiple sclerosis (MS). Without oral supplementation, systemic kynurenine levels decrease during the initiation phase of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, indicating systemic activation of tryptophan metabolism. Daily oral gavage of up to 10 mg/mouse/day was safe and increased serum kynurenine levels by more than 20-fold for more than 3 h after the gavage. While this treatment resulted in suppression of myelin-specific Th1 responses, there was no relevant impact on clinical disease activity. These data show that oral trp supplementation at subtoxic concentrations suppresses antigen-specific Th1 responses, but suggest that the increase in trp metabolites is not sustained enough to impact neuroinflammation.

Reflection and Phase Matching in Plasmonic Gold Tapers.

We investigate different dynamic mechanisms, reflection and phase matching, of surface plasmons in a three-dimensional single-crystalline gold taper excited by relativistic electrons. Plasmonic modes of gold tapers with various opening angles from 5° to 47° are studied both experimentally and theoretically, by means of electron energy-loss spectroscopy and finite-difference time-domain numerical calculations, respectively. Distinct resonances along the taper shaft are observed in tapers independent of opening angles. We show that, despite their similarity, the origin of these resonances is different at different opening angles and results from a competition between two coexisting mechanisms. For gold tapers with large opening angles (above ∼20°), phase matching between the electron field and that of higher-order angular momentum modes of the taper is the dominant contribution to the electron energy-loss because of the increasing interaction length between electron and the taper near-field. In contrast, reflection from the taper apex dominates the EELS contrast in gold tapers with small opening angles (below ∼10°). For intermediate opening angles, a gradual transition of these two mechanisms was observed.

Evaluating acellular versus cellular perfusate composition during prolonged ex vivo lung perfusion after initial cold ischaemia for 24 hours.

Normothermic ex vivo lung perfusion (EVLP) has developed as a powerful technique to evaluate particularly marginal donor lungs prior to transplantation. In this study, acellular and cellular perfusate compositions were compared in an identical experimental setting as no consensus has been reached on a preferred technique yet. Porcine lungs underwent EVLP for 12 h on the basis of an acellular or a cellular perfusate composition after 24 h of cold ischaemia as defined organ stress. During perfusion, haemodynamic and respiratory parameters were monitored. After EVLP, the lung condition was assessed by light and transmission electron microscopy. Aerodynamic parameters did not show significant differences between groups and remained within the in vivo range during EVLP. Mean oxygenation indices were 491 ± 39 in the acellular group and 513 ± 53 in the cellular group. Groups only differed significantly in terms of higher pulmonary artery pressure and vascular resistance in the cellular group. Lung histology and ultrastructure were largely well preserved after prolonged EVLP and showed only minor structural alterations which were similarly present in both groups. Prolonged acellular and cellular EVLP for 12 h are both feasible with lungs prechallenged by ischaemic organ stress. Physiological and ultrastructural analysis showed no superiority of either acellular or cellular perfusate composition.

Protein kinase Cß as a therapeutic target stabilizing blood-brain barrier disruption in experimental autoimmune encephalomyelitis.

Disruption of the blood-brain barrier (BBB) is a hallmark of acute inflammatory lesions in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis. This disruption may precede and facilitate the infiltration of encephalitogenic T cells. The signaling events that lead to this BBB disruption are incompletely understood but appear to involve dysregulation of tight-junction proteins such as claudins. Pharmacological interventions aiming at stabilizing the BBB in MS might have therapeutic potential. Here, we show that the orally available small molecule LY-317615, a synthetic bisindolylmaleimide and inhibitor of protein kinase Cß, which is clinically under investigation for the treatment of cancer, suppresses the transmigration of activated T cells through an inflamed endothelial cell barrier, where it leads to the induction of the tight-junction molecules zona occludens-1, claudin 3, and claudin 5 and other pathways critically involved in transendothelial leukocyte migration. Treatment of mice with ongoing experimental autoimmune encephalomyelitis with LY-317615 ameliorates inflammation, demyelination, axonal damage, and clinical symptoms. Although LY-317615 dose-dependently suppresses T-cell proliferation and cytokine production independent of antigen specificity, its therapeutic effect is abrogated in a mouse model requiring pertussis toxin. This abrogation indicates that the anti-inflammatory and clinical efficacy is mainly mediated by stabilization of the BBB, thus suppressing the transmigration of encephalitogenic T cells. Collectively, our data suggest the involvement of endothelial protein kinase Cß in stabilizing the BBB in autoimmune neuroinflammation and imply a therapeutic potential of BBB-targeting agents such as LY-317615 as therapeutic approaches for MS.

Toward plasmonics with nanometer precision: nonlinear optics of helium-ion milled gold nanoantennas.

Plasmonic nanoantennas are versatile tools for coherently controlling and directing light on the nanoscale. For these antennas, current fabrication techniques such as electron beam lithography (EBL) or focused ion beam (FIB) milling with Ga(+)-ions routinely achieve feature sizes in the 10 nm range. However, they suffer increasingly from inherent limitations when a precision of single nanometers down to atomic length scales is required, where exciting quantum mechanical effects are expected to affect the nanoantenna optics. Here, we demonstrate that a combined approach of Ga(+)-FIB and milling-based He(+)-ion lithography (HIL) for the fabrication of nanoantennas offers to readily overcome some of these limitations. Gold bowtie antennas with 6 nm gap size were fabricated with single-nanometer accuracy and high reproducibility. Using third harmonic (TH) spectroscopy, we find a substantial enhancement of the nonlinear emission intensity of single HIL-antennas compared to those produced by state-of-the-art gallium-based milling. Moreover, HIL-antennas show a vastly improved polarization contrast. This superior nonlinear performance of HIL-derived plasmonic structures is an excellent testimonial to the application of He(+)-ion beam milling for ultrahigh precision nanofabrication, which in turn can be viewed as a stepping stone to mastering quantum optical investigations in the near-field.

Fractal analysis of extracellular matrix for observer-independent quantification of intestinal fibrosis in Crohn's disease.

Prevention of intestinal fibrosis remains an unresolved problem in the treatment of Crohn's disease (CD), as specific antifibrotic therapies are not yet available. Appropriate analysis of fibrosis severity is essential for assessing the therapeutic efficacy of potential antifibrotic drugs. The aim of this study was to develop an observer-independent method to quantify intestinal fibrosis in surgical specimens from patients with CD using structural analysis of the extracellular matrix (ECM). We performed fractal analysis in fibrotic and control histological sections of patients with surgery for CD (n = 28). To specifically assess the structure of the collagen matrix, polarized light microscopy was used. A score to quantify collagen fiber alignment and the color of the polarized light was established. Fractal dimension as a measure for the structural complexity correlated significantly with the histological fibrosis score whereas lacunarity as a measure for the compactness of the ECM showed a negative correlation. Polarized light microscopy to visualize the collagen network underlined the structural changes in the ECM network in advanced fibrosis. In conclusion, observer-independent quantification of the structural complexity of the ECM by fractal analysis is a suitable method to quantify the degree of intestinal fibrosis in histological samples from patients with CD.

Surface charges of the membrane crucially affect regulation of Na,K-ATPase by phospholemman (FXYD1).

The human α1/His10-ß1 isoform of Na,K-ATPase has been reconstituted as a complex with and without FXYD1 into proteoliposomes of various lipid compositions in order to study the effect of the regulatory subunit on the half-saturating Na⁺ concentration (K(½)) of Na⁺ ions for activation of the ion pump. It has been shown that the fraction of negatively charged lipid in the bilayer crucially affects the regulatory properties. At low concentrations of the negatively charged lipid DOPS (<10 %), FXYD1 increases K(½) of Na⁺ ions for activation of the ion pump. Phosphorylation of FXYD1 by protein kinase A at Ser68 abrogates this effect. Conversely, for proteoliposomes made with high concentrations of DOPS (>10 %), little or no effect of FXYD1 on the K(½) of Na⁺ ions is observed. Depending on ionic strength and lipid composition of the proteoliposomes, FXYD1 can alter the K(½) of Na⁺ ions by up to twofold. We propose possible molecular mechanisms to explain the regulatory effects of FXYD1 and the influence of charged lipid and protein phosphorylation. In particular, the positively charged C-terminal helix of FXYD1 appears to be highly mobile and may interact with the cytoplasmic N domain of the α-subunit, the interaction being strongly affected by phosphorylation at Ser68 and the surface charge of the membrane.

Wave front adaptation using a deformable mirror for adiabatic nanofocusing along an ultrasharp gold taper.

We describe and demonstrate the use of an adaptive wave front optimization scheme for enhancing the efficiency of adiabatic nanofocusing of surface plasmon polariton (SPP) waves along an ultrasharp conical gold taper. Adiabatic nanofocusing is an emerging and promising scheme for controlled focusing of far field light into nanometric volumes. It comprises three essential steps: SPP excitation by coupling far field light to an SPP waveguide, SPP propagation along the waveguide and adiabatic SPP nanofocusing towards a geometric singularity. For commonly used complex waveguide geometries, such as, e.g., conical metal tapers, a realistic modeling and efficiency optimization is challenging. Here, we use a deformable mirror to adaptively control the wave front of the incident far field light. We demonstrate an eight-fold enhancement in nanofocusing efficiency and analyze the shape of the resulting optimized wave front. The introduced wave front optimization scheme is of general interest for guiding and controlling light on the nanoscale.

Individualized flow-controlled versus conventional pressure-controlled ventilation in on-pump heart surgery (FLOWVENTIN HEARTSURG): study protocol for a randomized controlled trial.

BACKGROUND: In on-pump cardiac surgery, lungs are at high risk of periprocedural organ impairment because of atelectasis formation, ventilator-induced lung injury, and hyperinflammation due to the cardiopulmonary bypass which results in postoperative pulmonary complications in half of this patient population. The new ventilation mode flow-controlled ventilation (FCV) uniquely allows full control of ins- and expiratory airway flows. This approach reduces the mechanical power of invasive ventilation as a possible cause of ventilator-induced lung injury. The scope of FLOWVENTIN HEARTSURG is to compare perioperative individualized FCV with best clinical practice pressure-controlled ventilation (PVC) modes in patients with elective on-pump cardiac surgery procedures. We hypothesize that the postoperative inflammatory response can be reduced by the perioperative application of FCV compared to PCV. METHODS: FLOWVENTIN HEARTSURG is a single-center, randomized, parallel-group trial with two intervention arms: perioperative PCV modes (n = 70, PCV group) with an individualized positive end-expiratory pressure (PEEP) and a tidal volume of 6-8 ml/kg predicted bodyweight compared to perioperative FCV (n = 70, FCV group) with an individualized PEEP and driving pressure, resulting in a liberal tidal volume. As the primary study endpoint interleukin 8 plasma level is assessed 6 h after cardiopulmonary bypass as a surrogate biomarker of systemic and pulmonary inflammation. As secondary aims clinically relevant patient outcomes are analyzed, e.g., perioperative lung function regarding oxygenation indices, postoperative pulmonary and extra-pulmonary complications, SIRS-free days as well as ICU and total inpatient stays. As additional sub-studies with an exploratory approach perioperative right ventricular function parameters are assessed by echocardiography and perioperative lung aeration by electrical impedance tomography. DISCUSSION: Current paradigms regarding protective low tidal volume ventilation are consciously left in the FCV intervention group in order to reduce mechanical power as a determinant of ventilator-induced lung injury in this high-risk patient population and procedures. This approach will be compared in a randomized controlled trial with current best clinical practice PCV in FLOWVENTIN HEARTSURG. TRIAL REGISTRATION: German Clinical Trials Register DRKS00018956 . Registered on 12 June 2020 (Version 1), last update on 22 August 2022 (Version 4).

Interaction of Different Charged Polymers with Potassium Ions and Their Effect on the Yield Stress of Highly Concentrated Glass Bead Suspensions.

The interaction of different charged polymers, namely anionic polycarboxylate superplasticizer (PCE) and neutral polyethylene glycol (PEG) with potassium ions, and their effect on the yield stress of highly concentrated glass bead suspension (GBS), were studied under different concentrations of potassium ions ([K+]). It was found that, compared to the neutral PEG, the negatively charged PCE can be adsorbed on glass beads (GB), and then decreases the yield stress of GBS. The increasing concentration of free polymer in the interstitial liquid phase with the increased polymer dosage leads to the higher yield stress of GBS, which may be caused by the higher depletion force. In addition, this effect is also related to the charge density of the polymer and the [K+] in the solution. Along with the increase in [K+], the yield stress of GBS increases significantly with the addition of PCE, but this cannot be observed with PEG, which indicates that potassium ions can interact with negatively charged PCE instead of the neutral PEG. At last, the interparticle forces between two single GB with adsorbed PCE in solutions containing [K+] and PCE were measured by colloidal probe atomic force microscopy to better understand the interaction of the charged polymer with counterions.

Effects of immediate versus delayed ex-vivo lung perfusion in a porcine cardiac arrest donation model.

OBJECTIVE: Ex-vivo lung perfusion is a promising tool to evaluate and recondition marginal donor lungs usually after a cold static preservation. The concept of continuous organ perfusion is supposed to reduce ischemic damage; however, the optimal perfusion protocol has not been established yet. The aim of this study was to compare immediate ex-vivo lung perfusion (I-EVLP) to delayed ex-vivo lung perfusion (D-EVLP) after a certain cold static preservation period on lung function in a large animal model. METHODS: In a porcine model, lungs were procured after circulatory death and 60 min of no-touch warm ischemia. Lungs were preserved with single-flush cold low potassium dextran solution and prepared either for I-EVLP (n = 8) or stored cold for 9 h with subsequent D-EVLP (n = 8). Functional outcomes and morphology were compared during 4 h of ex-vivo lung perfusion, using STEEN SolutionTM as perfusion solution. RESULTS: Pulmonary functional data, perfusate activities of lactate dehydrogenase, alkaline phosphatase, and products of lipid peroxidation did not differ significantly. There was a trend toward lower wet-dry ratio (I-EVLP: 13.4 ± 2.9; D-EVLP: 9.1 ± 2.5) and higher ΔpO2 in D-EVLP group (I-EVLP: 209 ± 51.6 mmHg; D-EVLP: 236.3 ± 47.3 mmHg). CONCLUSION: In this donation-after-circulatory-death model, 9 h of cold static preservation followed by ex-vivo lung perfusion results in comparable pulmonary function to I-EVLP as indicated by oxygenation capacities and wet-dry ratio. Our findings indicate that prolonged cold static preservation prior to ex-vivo lung perfusion is as safe and effective as I-EVLP in the procurement of donor lungs.

Far-Field Radiation of Three-Dimensional Plasmonic Gold Tapers near Apexes.

Three-dimensional plasmonic gold tapers are widely used structures in nano-optics for achieving imaging at the nanometer scale, enhanced spectroscopy, confined light sources, and ultrafast photoelectron emission. To understand their radiation properties further, especially in the proximity of the apex at the nanoscale, we employ cathodoluminescence spectroscopy with high spatial and energy resolution. The plasmon-induced radiation in the visible spectral range from three-dimensional gold tapers with opening angles of 13° and 47° is investigated under local electron excitation. We observe a much weaker radiation from the apex of the 13° taper than from that of the 47° taper. By means of finite-difference time-domain simulations we show that for small opening angles plasmon modes that are created at the apex are efficiently guided along the taper shaft. In contrast for tapers with larger opening angles, generated plasmon polaritons experience larger radiation damping. Interestingly, we find for both tapers that the most intense radiation comes from locations a few hundreds of nanometers behind the apexes, instead of exactly at the apexes. Our findings provide useful details for the design of plasmonic gold tapers as confined light sources or light absorbers.

Vectorial near-field coupling.

The coherent exchange of optical near fields between two neighbouring dipoles plays an essential role in the optical properties, quantum dynamics and thus the function of many naturally occurring and artificial nanosystems. These interactions are challenging to quantify experimentally. They extend over only a few nanometres and depend sensitively on the detuning, dephasing and relative orientation (that is, the vectorial properties) of the coupled dipoles. Here, we introduce plasmonic nanofocusing spectroscopy to record coherent light scattering spectra with 5 nm spatial resolution from the apex of a conical gold nanotaper. The apex is excited solely by evanescent fields and coupled to plasmon resonances in a single gold nanorod. We resolve resonance energy shifts and line broadenings as a function of dipole distance and relative orientation. We demonstrate how these phenomena arise from mode couplings between different vectorial components of the interacting optical near fields, specifically from the coupling of the nanorod to both transverse and longitudinal polarizabilities of the taper apex.