Classification with a disordered dopant-atom network in silicon.

Classification is an important task at which both biological and artificial neural networks excel1,2. In machine learning, nonlinear projection into a high-dimensional feature space can make data linearly separable3,4, simplifying the classification of complex features. Such nonlinear projections are computationally expensive in conventional computers. A promising approach is to exploit physical materials systems that perform this nonlinear projection intrinsically, because of their high computational density5, inherent parallelism and energy efficiency6,7. However, existing approaches either rely on the systems' time dynamics, which requires sequential data processing and therefore hinders parallel computation5,6,8, or employ large materials systems that are difficult to scale up7. Here we use a parallel, nanoscale approach inspired by filters in the brain1 and artificial neural networks2 to perform nonlinear classification and feature extraction. We exploit the nonlinearity of hopping conduction9-11 through an electrically tunable network of boron dopant atoms in silicon, reconfiguring the network through artificial evolution to realize different computational functions. We first solve the canonical two-input binary classification problem, realizing all Boolean logic gates12 up to room temperature, demonstrating nonlinear classification with the nanomaterial system. We then evolve our dopant network to realize feature filters2 that can perform four-input binary classification on the Modified National Institute of Standards and Technology handwritten digit database. Implementation of our material-based filters substantially improves the classification accuracy over that of a linear classifier directly applied to the original data13. Our results establish a paradigm of silicon-based electronics for small-footprint and energy-efficient computation14.

Ballistic Phonons in Ultrathin Nanowires.

According to Fourier's law, a temperature difference across a material results in a linear temperature profile and a thermal conductance that decreases inversely proportional to the system length. These are the hallmarks of diffusive heat flow. Here, we report heat flow in ultrathin (25 nm) GaP nanowires in the absence of a temperature gradient within the wire and find that the heat conductance is independent of wire length. These observations deviate from Fourier's law and are direct proof of ballistic heat flow, persisting for wire lengths up to at least 15 µm at room temperature. When doubling the wire diameter, a remarkably sudden transition to diffusive heat flow is observed. The ballistic heat flow in the ultrathin wires can be modeled within Landauer's formalism by ballistic phonons with an extraordinarily long mean free path.

Protease-activated receptor 2 deficiency mediates cardiac fibrosis and diastolic dysfunction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) and pathological cardiac aging share a complex pathophysiology, including extracellular matrix remodelling (EMR). Protease-activated receptor 2 (PAR2) deficiency is associated with EMR. The roles of PAR1 and PAR2 have not been studied in HFpEF, age-dependent cardiac fibrosis, or diastolic dysfunction (DD). METHODS AND RESULTS: Evaluation of endomyocardial biopsies from patients with HFpEF (n = 14) revealed that a reduced cardiac PAR2 expression was associated with aggravated DD and increased myocardial fibrosis (r = -0.7336, P = 0.0028). In line, 1-year-old PAR2-knockout (PAR2ko) mice suffered from DD with preserved systolic function, associated with an increased age-dependent α-smooth muscle actin expression, collagen deposition (1.7-fold increase, P = 0.0003), lysyl oxidase activity, collagen cross-linking (2.2-fold increase, P = 0.0008), endothelial activation, and inflammation. In the absence of PAR2, the receptor-regulating protein caveolin-1 was down-regulated, contributing to an augmented profibrotic PAR1 and transforming growth factor beta (TGF-ß)-dependent signalling. This enhanced TGF-ß/PAR1 signalling caused N-proteinase (ADAMTS3) and C-proteinase (BMP1)-related increased collagen I production from cardiac fibroblasts (CFs). PAR2 overexpression in PAR2ko CFs reversed these effects. The treatment with the PAR1 antagonist, vorapaxar, reduced cardiac fibrosis by 44% (P = 0.03) and reduced inflammation in a metabolic disease model (apolipoprotein E-ko mice). Patients with HFpEF with upstream PAR inhibition via FXa inhibitors (n = 40) also exhibited reduced circulating markers of fibrosis and DD compared with patients treated with vitamin K antagonists (n = 20). CONCLUSIONS: Protease-activated receptor 2 is an important regulator of profibrotic PAR1 and TGF-ß signalling in the heart. Modulation of the FXa/FIIa-PAR1/PAR2/TGF-ß-axis might be a promising therapeutic approach to reduce HFpEF.

Charge Transport by Superexchange in Molecular Host-Guest Systems.

Charge transport in disordered organic semiconductors is generally described as a result of incoherent hopping between localized states. In this work, we focus on multicomponent emissive host-guest layers as used in organic light-emitting diodes (OLEDs), and show using multiscale ab initio based modeling that charge transport can be significantly enhanced by the coherent process of molecular superexchange. Superexchange increases the rate of emitter-to-emitter hopping, in particular if the emitter molecules act as relatively deep trap states, and allows for percolation path formation in charge transport at low guest concentrations.

Nicotinamide phosphoribosyltransferase/pre-B-cell colony enhancing factor/visfatin plasma levels and clinical outcome in patients with dilated cardiomyopathy.

BACKGROUND: Nicotinamide phosphoribosyltransferase (Nampt) is an enzyme involved in nicotinamide adenine dinucleotide biosynthesis. Nampt functions as gatekeeper of energy status and survival in cardiac myocytes in animal models of ischemia-reperfusion and might regulate inflammatory processes. Therefore, we performed for the 1st time a clinical study to determine the effects of Nampt on cardiac function in patients with nonischemic dilated (DCM) and inflammatory (DCMi) cardiomyopathy. METHODS AND RESULTS: A total of 113 patients were enrolled in the study and classified into control (n = 25), DCM (n = 38), and DCMi (n = 50) groups. Cardiac functional and inflammatory parameters as well as plasma Nampt and cardiac mRNA and protein Nampt expression were determined at baseline and follow-up after 6 months. Patients with DCM (1.04 ± 0.8 ng/mL; P < .001) and DCMi (1.07 ± 0.7 ng/mL; P < .001) showed significantly increased Nampt plasma concentrations at baseline compared with the control group (0.57 ± 0.5 ng/mL). Patients with higher Nampt concentrations in both heart failure groups showed significant better improvement of cardiac functional parameters (correlation between Nampt plasma levels and the change of left ventricular ejection fraction after 6 months: DCM: r = 0.698, P < .001; DCMi: r = 0.503, P < .001). Moreover, cardiac inflammation did not influence Nampt expression, and Nampt concentrations did not modulate cardiac inflammation in DCMi. A multivariate linear regression model revealed high plasma Nampt expression to contribute to better improvement of cardiac function in patients of both heart failure groups. Moreover, heart failure patients with high plasma Nampt levels showed suppressed cardiac TNF-α and IL-6 mRNA expression after 6 months' follow-up as well as lower B-type natriuretic peptide levels compared with heart failure patients with low Nampt plasma concentrations. CONCLUSIONS: High Nampt expression in patients with nonischemic DCM and DCMi is associated with a favorable outcome and improvement in functional status.

The effect of clopidogrel on platelet activity in patients with and without type-2 diabetes mellitus: a comparative study.

BACKGROUND: Although antiplatelet therapy involving clopidogrel is a standard treatment for preventing cardiovascular events after coronary stent implantation, patients can display differential responses. Here, we assessed the effectiveness of clopidogrel on platelet function inhibition in subjects with and without type-2 diabetes and stable coronary artery disease. In addition, we investigated the correlation between platelet function and routine clinical parameters. METHODS: A total of 64 patients with stable coronary heart disease were enrolled in the study. Among these, 32 had known type-2 diabetes, whereas the remaining 32 subjects were non-diabetics (control group). A loading dose of 300 mg clopidogrel was given to clopidogrel-naïve patients (13 patients in the diabetes group and 14 control patients). All patients were given a daily maintenance dose of 75 mg clopidogrel. In addition, all patients received 100 mg ASA per day. Agonist-induced platelet aggregation measurements were performed on hirudin-anticoagulated blood using an impedance aggregometer (Multiple Platelet Function Analyzer, Dynabyte, Munich, Germany). Blood samples were drawn from the antecubital vein 24 h after coronary angiography with percutaneous coronary intervention. The platelets were then stimulated with ADP alone or ADP and prostaglandin-E (ADP and ADP-PGE tests, respectively) in order to evaluate clopidogrel-mediated inhibition of platelet function. The effectiveness of ASA was measured by stimulation with arachidonic acid (ASPI test). In addition, maximal platelet aggregation was assessed via stimulation with thrombin receptor-activating peptide (TRAP test). RESULTS: Patients with diabetes exhibited significantly less inhibition of platelet function than patients without diabetes (ADP-PGE test p = 0.003; ASPI test p = 0.022). Administering a clopidogrel loading dose of 300 mg did not result in a lower level of ADP-PGE-induced platelet reactivity in comparison to the use of a 75 mg maintenance dose. Moreover, we observed that ADP-PGE-induced platelet inhibition was positively correlated with fasting blood glucose and HbA1c (p < 0.01). CONCLUSIONS: Patients with type-2 diabetes exhibited increased platelet reactivity compared to patients without diabetes despite combined treatment with clopidogrel and ASA. Using a loading dose of clopidogrel rather than small daily doses was not sufficient for adequately overcoming increased platelet reactivity in patients with type-2 diabetes, highlighting the need for more effective anti-platelet drugs for such patients.

Molecular-scale simulation of electroluminescence in a multilayer white organic light-emitting diode.

In multilayer white organic light-emitting diodes the electronic processes in the various layers--injection and motion of charges as well as generation, diffusion and radiative decay of excitons--should be concerted such that efficient, stable and colour-balanced electroluminescence can occur. Here we show that it is feasible to carry out Monte Carlo simulations including all of these molecular-scale processes for a hybrid multilayer organic light-emitting diode combining red and green phosphorescent layers with a blue fluorescent layer. The simulated current density and emission profile are shown to agree well with experiment. The experimental emission profile was obtained with nanometre resolution from the measured angle- and polarization-dependent emission spectra. The simulations elucidate the crucial role of exciton transfer from green to red and the efficiency loss due to excitons generated in the interlayer between the green and blue layers. The perpendicular and lateral confinement of the exciton generation to regions of molecular-scale dimensions revealed by this study demonstrate the necessity of molecular-scale instead of conventional continuum simulation.

Thermodynamic Origin of the Photostability of the Two-Dimensional Perovskite PEA2Pb(I1-x Br x )4.

The two-dimensional (2D) mixed halide perovskite PEA2Pb(I1-x Br x )4 exhibits high phase stability under illumination as compared to the three-dimensional (3D) counterpart MAPb(I1-x Br x )3. We explain this difference using a thermodynamic theory that considers the sum of a compositional and a photocarrier free energy. Ab initio calculations show that the improved compositional phase stability of the 2D perovskite is caused by a preferred I-Br distribution, leading to a much lower critical temperature for halide segregation in the dark than for the 3D perovskite. Moreover, a smaller increase of the band gap with Br concentration x and a markedly shorter photocarrier lifetime in the 2D perovskite reduce the driving force for phase segregation under illumination, enhancing the photostability.

Adiponectin expression in patients with inflammatory cardiomyopathy indicates favourable outcome and inflammation control.

AIMS: Circulating adiponectin (APN) is an immunomodulatory, pro-angiogenic, and anti-apoptotic adipocytokine protecting against acute viral heart disease and preventing pathological remodelling after cardiac injury. The purpose of this study was to describe the regulation and effects of APN in patients with inflammatory cardiomyopathy (DCMi). METHODS AND RESULTS: Adiponectin expression and outcome were assessed in 173 patients with DCMi, 30 patients with non-inflammatory DCM, and 30 controls. Mechanistic background of these findings was addressed in murine experimental autoimmune myocarditis (EAM), a model of human DCMi, and further elucidated in vitro. Adiponectin plasma concentrations were significantly higher in DCMi compared with DCM or controls, i.e. 6.8 ± 3.9 µg/mL vs. 5.4 ± 3.6 vs. 4.76 ± 2.5 µg/mL (P< 0.05, respectively) and correlated significantly with cardiac mononuclear infiltrates (CD3+: r(2)= 0.025, P= 0.038; CD45R0+: r(2)= 0.058, P= 0.018). At follow-up, DCMi patients with high APN levels showed significantly increased left ventricular ejection fraction improvement, decreased left ventricular end-diastolic diameter, and reduced cardiac inflammatory infiltrates compared with patients with low APN levels. A multivariate linear regression analysis implicated APN as an independent prognostic factor for inhibition of cardiac inflammation. In accordance with these findings in human DCMi, EAM mice exhibited elevated plasma APN. Adiponectin gene transfer led to significant downregulation of key inflammatory mediators promoting disease. Mechanistically, APN acted as a negative regulator of T cells by reducing antigen specific expansion (P< 0.01) and suppressed TNFα-mediated NFκB activation (P< 0.01) as well as release of reactive oxygen species in cardiomyocytes. CONCLUSION: Our results implicate that APN acts as endogenously upregulated anti-inflammatory cytokine confining cardiac inflammation and progression in DCMi.

Leptin and resistin induce increased procoagulability in diabetes mellitus.

BACKGROUND: Patients with diabetes mellitus (DM) suffer from an increased risk of cardiovascular events caused by thrombotic conditions. Adipose tissue might play a crucial role in this pathogenesis by synthesis of procoagulant mediators. This study was performed to elucidate the role of the adipocytokines leptin and resistin in the development of hypercoagulability and hypofibrinolysis under diabetic conditions. METHODS: Sixty two patients with or without DM were included in our study to measure leptin, resistin and tissue factor (TF) plasma concentrations. Moreover, flow chamber experiments were performed to assess factor Xa and plasmin activity on the surface of HUVECs. Western blot and real-time PCR were performed to determine mRNA and protein expression of main factors of the coagulation and fibrinolytic system. RESULTS: Patients with diabetes showed increased levels of leptin and resistin (leptin: 25.69±13.9 vs. 15.98±17.5 ng/mL, p<0.05; resistin: 2.61±0.6 vs. 1.19±0.7 ng/mL, p<0.05), which were positively correlated with TF. In vitro, leptin and resistin induced increased factor Xa activity (leptin: 4.29±0.57-fold, p<0.05; resistin 4.19±0.7-fold, p<0.05 vs. control) on HUVECs as also reflected by elevated TF mRNA and protein expression. Moreover, stimulatory (plasminogen activator inhibitor 1) and inhibitory (tissue plasminogen activator) mediators of the fibrinolytic cascade were induced by leptin and resistin, leading to a balanced plasmin activity regulation. CONCLUSIONS: Leptin and resistin lead to a procoagulant state in HUVECs by inducing TF expression. This mechanism might be one explanation for the prothrombotic state observed under diabetic conditions.

Unified theory for light-induced halide segregation in mixed halide perovskites.

Mixed halide perovskites that are thermodynamically stable in the dark demix under illumination. This is problematic for their application in solar cells. We present a unified thermodynamic theory for this light-induced halide segregation that is based on a free energy lowering of photocarriers funnelling to a nucleated phase with different halide composition and lower band gap than the parent phase. We apply the theory to a sequence of mixed iodine-bromine perovskites. The spinodals separating metastable and unstable regions in the composition-temperature phase diagrams only slightly change under illumination, while light-induced binodals separating stable and metastable regions appear signalling the nucleation of a low-band gap iodine-rich phase. We find that the threshold photocarrier density for halide segregation is governed by the band gap difference of the parent and iodine-rich phase. Partial replacement of organic cations by cesium reduces this difference and therefore has a stabilizing effect.

Effect of Light-Induced Halide Segregation on the Performance of Mixed-Halide Perovskite Solar Cells.

Light-induced halide segregation hampers obtaining stable wide-band-gap solar cells based on mixed iodide-bromide perovskites. So far, the effect of prolonged illumination on the performance of mixed-halide perovskite solar cells has not been studied in detail. It is often assumed that halide segregation leads to a loss of open-circuit voltage. By simultaneously recording changes in photoluminescence and solar cell performance under prolonged illumination, we demonstrate that cells instead deteriorate by a loss of short-circuit current density and that the open-circuit voltage is less affected. The concurrent red shift, increased lifetime, and higher quantum yield of photoluminescence point to the formation of relatively emissive iodide-rich domains under illumination. Kinetic Monte Carlo simulations provide an atomistic insight into their formation via exchange of bromide and iodide, mediated by halide vacancies. Localization of photogenerated charge carriers in low-energy iodide-rich domains and subsequent recombination cause reduced photocurrent and red-shifted photoluminescence. The loss in photovoltaic performance is diminished by partially replacing organic cations by cesium ions. Ultrasensitive photocurrent spectroscopy shows that cesium ions result in a lower density of sub-band-gap defects and suppress defect growth under illumination. These defects are expected to play a role in the development and recovery of light-induced compositional changes.

High energy acceptor states strongly enhance exciton transfer between metal organic phosphorescent dyes.

Exciton management in organic light-emitting diodes (OLEDs) is vital for improving efficiency, reducing device aging, and creating new device architectures. In particular in white OLEDs, exothermic Förster-type exciton transfer, e.g. from blue to red emitters, plays a crucial role. It is known that a small exothermicity partially overcomes the spectral Stokes shift, enhancing the fraction of resonant donor-acceptor pair states and thus the Förster transfer rate. We demonstrate here a second enhancement mechanism, setting in when the exothermicity exceeds the Stokes shift: transfer to multiple higher-lying electronically excited states of the acceptor molecules. Using a recently developed computational method we evaluate the Förster transfer rate for 84 different donor-acceptor pairs of phosphorescent emitters. As a result of the enhancement the Förster radius tends to increase with increasing exothermicity, from around 1 nm to almost 4 nm. The enhancement becomes particularly strong when the excited states have a large spin-singlet character.

A deep-learning approach to realizing functionality in nanoelectronic devices.

Many nanoscale devices require precise optimization to function. Tuning them to the desired operation regime becomes increasingly difficult and time-consuming when the number of terminals and couplings grows. Imperfections and device-to-device variations hinder optimization that uses physics-based models. Deep neural networks (DNNs) can model various complex physical phenomena but, so far, are mainly used as predictive tools. Here, we propose a generic deep-learning approach to efficiently optimize complex, multi-terminal nanoelectronic devices for desired functionality. We demonstrate our approach for realizing functionality in a disordered network of dopant atoms in silicon. We model the input-output characteristics of the device with a DNN, and subsequently optimize control parameters in the DNN model through gradient descent to realize various classification tasks. When the corresponding control settings are applied to the physical device, the resulting functionality is as predicted by the DNN model. We expect our approach to contribute to fast, in situ optimization of complex (quantum) nanoelectronic devices.

Optical spectra and stokes shift in double-stranded helical supramolecular assemblies.

We study the photoluminescence from helical MOPV4 aggregates using a model that includes excitonic coupling, exciton-phonon coupling, and spatially correlated disorder in the chromophore transition energies. The helical aggregates consist of stacked dimers of MOPV4 chromophores. We have modeled these helical stacks as double-stranded aggregates, allowing us to investigate the effect of correlated disorder within the dimers on emission. We have studied the dependence of the Stokes shift, the emission line widths, and the ratio of the 0-0 to 0-1 emission peaks on the aggregate size and disorder. Our findings show that this peak ratio is quite insensitive to the aggregate size if the latter exceeds the coherence length of the emitting exciton. This makes this ratio a reliable probe for both disorder and the coherence length of the emitting exciton. We have found only a weak dependence of this peak ratio on the degree of correlation between the transition energies within each dimer, whereas such correlation has a large effect on the aggregate-size-dependent Stokes shift. By comparison with experiment, we have estimated the coherence length of the emitting exciton to be only one lattice spacing along the stacking direction. From our analysis of the Stokes shift we conclude that the exciton diffusion length is in the range 6-13 nm.

Equilibrated Charge Carrier Populations Govern Steady-State Nongeminate Recombination in Disordered Organic Solar Cells.

We employed bias-assisted charge extraction techniques to investigate the transient and steady-state recombination of photogenerated charge carriers in complete devices of a disordered polymer-fullerene blend. Charge recombination is shown to be dispersive, with a significant slowdown of the recombination rate over time, consistent with the results from kinetic Monte Carlo simulations. Surprisingly, our experiments reveal little to no contributions from early time recombination of nonequilibrated charge carriers to the steady-state recombination properties. We conclude that energetic relaxation of photogenerated carriers outpaces any significant nongeminate recombination under application-relevant illumination conditions. With equilibrated charges dominating the steady-state recombination, quasi-equilibrium concepts appear suited for describing the open-circuit voltage of organic solar cells despite pronounced energetic disorder.

Globular adiponectin but not full-length adiponectin induces increased procoagulability in human endothelial cells.

Adiponectin (APN), a recently discovered adipocytokine, is present in human serum in a full length (fAPN) and a globular form (gAPN). gAPN is a proteolytic cleavage product of fAPN and seems to show independent biological activities compared to the properties of fAPN. The influence of gAPN and fAPN on procoagulability of cells is still unknown. This study examined the effect of gAPN and fAPN on the expression of tissue factor (TF), the initiator of the extrinsic coagulation system, in human umbilical vein endothelial cells (HUVECs). TF activity was measured by a chromogenic assay, TF mRNA by real-time PCR and TF protein by western blot. We found TF activity to be increased after activation by gAPN (3 microg/mL) compared to a non-stimulated control (169.0+/-19.23 U versus 501.9+/-38.95 U, p<0.001). Furthermore, TF mRNA and TF protein was increased dose-dependently after gAPN stimulation. The gAPN-induced rise of TF activity and TF mRNA was significantly reduced by inhibition of the MAP kinases ERK1/2, p38 and JNK. Contrary to gAPN, stimulation with fAPN did not lead to these procoagulant effects. In conclusion, gAPN increased TF transcription, expression and activity in HUVECs. Therefore, our data support the theory that gAPN but not fAPN supports the cellular procoagulability via TF upregulation.

Photoluminescence spectra of self-assembling helical supramolecular assemblies: a theoretical study.

The reversible assembly of helical supramolecular polymers of chiral molecular building blocks is known to be governed by the interplay between mass action and the competition between weakly and strongly bound states of these building blocks. The highly co-operative transition from free monomers at high temperatures to long helical aggregates at low temperatures can be monitored by photoluminescence spectroscopy that probes the energetically lowest-lying optical excitations in the assemblies. In order to provide the interpretation of obtained spectroscopic data with a firm theoretical basis, we present a comprehensive model that combines a statistical theory of the equilibrium polymerization with a quantum-mechanical theory that not only accounts for the conformational properties of the assemblies but also describes the impact of correlated energetic disorder stemming from deformations within the chromophores and their interaction with solvent molecules. The theoretical predictions are compared to fluorescence spectra of chiral oligo(p-phenylene-vinylene) molecules in the solvent dodecane and we find them to qualitatively describe the red-shift of the main fluorescence peak and its decreasing intensity upon aggregation.

Stabilizing Lead-Free All-Inorganic Tin Halide Perovskites by Ion Exchange.

Because of its thermal stability, lead-free composition, and nearly ideal optical and electronic properties, the orthorhombic CsSnI3 perovskite is considered promising as a light absorber for lead-free all-inorganic perovskite solar cells. However, the susceptibility of this three-dimensional perovskite toward oxidation in air has limited the development of solar cells based on this material. Here, we report the findings of a computational study which identifies promising Rb y Cs1-y Sn(Br x I1-x )3 perovskites for solar cell applications, prepared by substituting cations (Rb for Cs) and anions (Br for I) in CsSnI3. We show the evolution of the material electronic structure as well as its thermal and structural stabilities upon gradual substitution. Importantly, we demonstrate how the unwanted yellow phase can be suppressed by substituting Br for I in CsSn(Br x I1-x )3 with x ≥ 1/3. We predict that substitution of Rb for Cs results in a highly homogeneous solid solution and therefore an improved film quality and applicability in solar cell devices.

Interstitial Occupancy by Extrinsic Alkali Cations in Perovskites and Its Impact on Ion Migration.

Recent success in achieving highly stable Rb-containing organolead halide perovskites has indicated the possibility of incorporating small monovalent cations, which cannot fit in the lead-halide cage with an appropriate tolerance factor, into the perovskite lattice while maintaining a pure stable "black" phase. In this study, through a combined experimental and theoretical investigation by density functional theory (DFT) calculations on the incorporation of extrinsic alkali cations (Rb+ , K+ , Na+ , and Li+ ) in perovskite materials, the size-dependent interstitial occupancy of these cations in the perovskite lattice is unambiguously revealed. Interestingly, DFT calculations predict the increased ion migration barriers in the lattice after the interstitial occupancy. To verify this prediction, ion migration behavior is characterized through hysteresis analysis of solar cells, electrical poling, temperature-dependent conductivity, and time-dependent photoluminescence measurements. The results collectively point to the suppression of ion migration after lattice interstitial occupancy by extrinsic alkali cations. The findings of this study provide new material design principles to manipulate the structural and ionic properties of multication perovskite materials.