11 TOPS photonic convolutional accelerator for optical neural networks.

Convolutional neural networks, inspired by biological visual cortex systems, are a powerful category of artificial neural networks that can extract the hierarchical features of raw data to provide greatly reduced parametric complexity and to enhance the accuracy of prediction. They are of great interest for machine learning tasks such as computer vision, speech recognition, playing board games and medical diagnosis1-7. Optical neural networks offer the promise of dramatically accelerating computing speed using the broad optical bandwidths available. Here we demonstrate a universal optical vector convolutional accelerator operating at more than ten TOPS (trillions (1012) of operations per second, or tera-ops per second), generating convolutions of images with 250,000 pixels-sufficiently large for facial image recognition. We use the same hardware to sequentially form an optical convolutional neural network with ten output neurons, achieving successful recognition of handwritten digit images at 88 per cent accuracy. Our results are based on simultaneously interleaving temporal, wavelength and spatial dimensions enabled by an integrated microcomb source. This approach is scalable and trainable to much more complex networks for demanding applications such as autonomous vehicles and real-time video recognition.

Identification of genome edited cells using CRISPRnano.

Genome engineering-induced cleavage sites can be resolved by non-homologous end joining (NHEJ) or homology-directed repair (HDR). Identifying genetically modified clones at the target locus remains an intensive and laborious task. Different workflows and software that rely on deep sequencing data have been developed to detect and quantify targeted mutagenesis. Nevertheless, these pipelines require high-quality reads generated by Next Generation Sequencing (NGS) platforms. Here, we have developed a robust, versatile, and easy-to-use computational webserver named CRISPRnano (www.CRISPRnano.de) that enables the analysis of low-quality reads generated by affordable and portable sequencers including Oxford Nanopore Technologies (ONT) devices. CRISPRnano allows fast and accurate identification, quantification, and visualization of genetically modified cell lines, it is compatible with NGS and ONT sequencing reads, and it can be used without an internet connection.

Ridge waveguide couplers with leaky mode resonator-like wavelength responses.

Integrated photonic resonators based on bound states in the continuum (BICs) on the silicon-on-insulator (SOI) platform have the potential for novel, mass-manufacturable resonant devices. While the nature of BIC-based ridge resonators requires the resonators to be extended in the (axial) propagation direction of the resonant mode, the requirement for excitation from the quasi-continuum extends the resonator structures also in the lateral dimensions, resulting in large device footprints. To overcome this footprint requirement, we investigate the translation of BIC-based ridge resonators into a guided mode system with finite lateral dimensions. We draw analogies between the resulting waveguide system and the BIC-based resonators and numerically demonstrate that, analog to the BIC-based resonators, such a waveguide system can exhibit spectrally narrow-band inversion of its transmissive behavior.

Ridge resonators with compact guided mode coupling.

Ridge resonators are a recently introduced integrated photonic circuit element based on bound states in the continuum (BICs) which can produce a single, sharp resonance over a broad wavelength range with high extinction ratio. However, to excite these resonators, a broad beam of laterally unbound slab mode is required, resulting in a large device footprint, which is not attractive for integrated photonic circuits. In this contribution, we propose and numerically validate a guided-mode waveguide structure that can be analogue to the BIC-based ridge resonators. Our simulations show that the proposed guided-mode waveguide structure can produce resonances with similar characteristics, yet with a significantly reduced footprint. Furthermore, we investigate the influence of the resonator's dimensions on the bandwidth of the resonance, demonstrating that resonances with Q-factors from low to very high (> 10000) are feasible. We believe that the reduced footprint and ability to design filters systematically make the guided-mode waveguide resonators an attractive photonic circuit component with particular value for foundry fabricated silicon photonic circuits.

Integrated lithium niobate optical mode (de)interleaver based on an asymmetric Y-junction.

Lithium niobate on insulator (LNOI) platforms promise unique advantages in realizing high-speed, large-capacity, and large-scale photonic integrated circuits (PICs) by leveraging lithium niobate's attractive material properties, which include electro-optic and nonlinear optic properties, low material loss, and a wide transparency window. Optical mode interleavers can increase the functionality of future PICs in LNOI by enabling optical mode division multiplexing (MDM) systems, allowing variable mode assignment while maintaining high channel utilization and capacity. In this Letter, we experimentally demonstrate an optical mode interleaver based on an asymmetric Y-junction on the LNOI platform, which exhibits an insertion loss of below 0.46 dB and modal cross talk of below -13.0 dB over a wavelength range of 1500-1600 nm. The demonstrated mode interleaver will be an attractive circuit component in future high-speed and large-capacity PICs due to its simple structure, scalability, and capacity for efficient and flexible mode manipulation on the LNOI platform.

Integrated lithium niobate polarization beam splitter based on a photonic-crystal-assisted multimode interference coupler.

Lithium niobate on insulator (LNOI) is a promising platform for high-speed photonic integrated circuits (PICs) that are used for communication systems due to the excellent electro-optic properties of lithium niobate (LN). In such circuits, the high-speed electro-optical modulators and switches need to be integrated with passive circuit components that are used for routing the optical signals. Polarization beam splitters (PBSs) are one of the fundamental passive circuit components for high-speed PICs that can be used to (de)multiplex two orthogonal polarization optical modes, enabling on-chip polarization division multiplexing (PDM) systems, which are suitable for enhancing the data capacity of PICs. In this Letter, we design and experimentally demonstrate a high-performance PBS constructed by a photonic crystal (PC)-assisted multimode interference (MMI) coupler. The measured polarization extinction ratio (ER) of the fabricated device is 15 dB in the wavelength range from 1525 to 1565 nm, which makes them suitable for the high-speed and large data capacity PICs required for future communication systems.

Synthesis of E- and Z-trisubstituted alkenes by catalytic cross-metathesis.

Catalytic cross-metathesis is a central transformation in chemistry, yet corresponding methods for the stereoselective generation of acyclic trisubstituted alkenes in either the E or the Z isomeric forms are not known. The key problems are a lack of chemoselectivity-namely, the preponderance of side reactions involving only the less hindered starting alkene, resulting in homo-metathesis by-products-and the formation of short-lived methylidene complexes. By contrast, in catalytic cross-coupling, substrates are more distinct and homocoupling is less of a problem. Here we show that through cross-metathesis reactions involving E- or Z-trisubstituted alkenes, which are easily prepared from commercially available starting materials by cross-coupling reactions, many desirable and otherwise difficult-to-access linear E- or Z-trisubstituted alkenes can be synthesized efficiently and in exceptional stereoisomeric purity (up to 98 per cent E or 95 per cent Z). The utility of the strategy is demonstrated by the concise stereoselective syntheses of biologically active compounds, such as the antifungal indiacen B and the anti-inflammatory coibacin D.

Molybdenum chloride catalysts for Z-selective olefin metathesis reactions.

The development of catalyst-controlled stereoselective olefin metathesis processes has been a pivotal recent advance in chemistry. The incorporation of appropriate ligands within complexes based on molybdenum, tungsten and ruthenium has led to reactivity and selectivity levels that were previously inaccessible. Here we show that molybdenum monoaryloxide chloride complexes furnish higher-energy (Z) isomers of trifluoromethyl-substituted alkenes through cross-metathesis reactions with the commercially available, inexpensive and typically inert Z-1,1,1,4,4,4-hexafluoro-2-butene. Furthermore, otherwise inefficient and non-stereoselective transformations with Z-1,2-dichloroethene and 1,2-dibromoethene can be effected with substantially improved efficiency and Z selectivity. The use of such molybdenum monoaryloxide chloride complexes enables the synthesis of representative biologically active molecules and trifluoromethyl analogues of medicinally relevant compounds. The origins of the activity and selectivity levels observed, which contradict previously proposed principles, are elucidated with the aid of density functional theory calculations.

Kinetically E-selective macrocyclic ring-closing metathesis.

Macrocyclic compounds are central to the development of new drugs, but preparing them can be challenging because of the energy barrier that must be surmounted in order to bring together and fuse the two ends of an acyclic precursor such as an alkene (also known as an olefin). To this end, the catalytic process known as ring-closing metathesis (RCM) has allowed access to countless biologically active macrocyclic organic molecules, even for large-scale production. Stereoselectivity is often critical in such cases: the potency of a macrocyclic compound can depend on the stereochemistry of its alkene; alternatively, one isomer of the compound can be subjected to stereoselective modification (such as dihydroxylation). Kinetically controlled Z-selective RCM reactions have been reported, but the only available metathesis approach for accessing macrocyclic E-olefins entails selective removal of the Z-component of a stereoisomeric mixture by ethenolysis, sacrificing substantial quantities of material if E/Z ratios are near unity. Use of ethylene can also cause adventitious olefin isomerization-a particularly serious problem when the E-alkene is energetically less favoured. Here, we show that dienes containing an E-alkenyl-B(pinacolato) group, widely used in catalytic cross-coupling, possess the requisite electronic and steric attributes to allow them to be converted stereoselectively to E-macrocyclic alkenes. The reaction is promoted by a molybdenum monoaryloxide pyrrolide complex and affords products at a yield of up to 73 per cent and an E/Z ratio greater than 98/2. We highlight the utility of the approach by preparing recifeiolide (a 12-membered-ring antibiotic) and pacritinib (an 18-membered-ring enzyme inhibitor), the Z-isomer of which is less potent than the E-isomer. Notably, the 18-membered-ring moiety of pacritinib-a potent anti-cancer agent that is in advanced clinical trials for treating lymphoma and myelofibrosis-was prepared by RCM carried out at a substrate concentration 20 times greater than when a ruthenium carbene was used.

Development of taste-masking microcapsules containing azithromycin by fluid bed coating for powder for suspension and in vivo evaluation.

This research aims to develop bitter taste-masking microcapsules containing azithromycin (AZI) by a simpler and familiar method, fluid-bed coating technology, in comparison with Zithromax®. Cores of microcapsules, AZI microparticles, were prepared by fluid-bed granulation, then taste-masking polymer was covered on by fluid-bed coating technique. Eudragit L100, Eudragit RL100, and ethyl cellulose in single and combined with Eudragit L100 and Eudragit E100 were used as taste-masking polymers. The obtained microcapsules were characterised by taste-masking ability, in vitro release, SEM, coating thickness, and coating efficiency. Combination of ethyl cellulose and Eudragit E100 (3:1) in coating thickness of 45.13 ± 2.12% w/w prevents AZI release from microcapsules below bitter taste threshold (1.78 ± 1.17 µg/ml). Bioavailability of powders containing AZI microcapsules and pH modulators (50 mg Na3PO4 and 35 mg Mg(OH)2) was not significantly different from the reference product (Zithromax®, Pfizer, New York, NY) in the rabbit model (p > 0.05). These results support the possibility of developing a generic product containing AZI.

A Novel Alginate Film Based on Nanocoating Approach for Enteric-Release Tablets.

The objective of this study was to propose a new coating film for biodegradable polymers and environmentally friendly processing. Here, a novel implementation of solid lipid nanoparticles (SLN) into a biodegradable alginate (ALG) film composition created a new gastric-resistant film for an enteric-release tablet. Experiments were performed on a water-soluble substance (thiamine nitrate) to characterize the effects of SLN upon the addition of the ALG coating formulation. The coated tablets or cast films were characterized based on delayed-release properties, surface morphology, moisture resistance, and chemical interactions. The SLN-ALG film displayed gastric-resistant properties (< 10% drug substance dissolved at pH 1.2) and rapid disintegration in the intestinal medium (pH 6.8). Morphological analysis using a microscope and scanning electron microscope confirmed the uniformity and smoothness of the SLN-ALG film, which improved the mechanical properties of the film. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated that SLN contributed to the formation of the film, which maintained free carboxylic groups, making the SLN-ALG film a higher acid resistance, but soluble in pH 6.8 buffer. These promising results suggest a novel nanotechnology-based coating formulation for various enteric-release dosage forms. Because of their biodegradability, the proposed ingredients and processes are safe and environment-friendly.

Coronary artery cavitation as a trigger for atherosclerotic plaque progression: a simplified numerical and computational fluid dynamic demonstration.

BACKGROUNDS: Coronary cavitation is supposed to be generated by both concentric and eccentric coronary artery stenosis which propagates downstream the vessel, creating microbubbles which exploded when the fluid pressure was lower than the vapor pressure at a local thermodynamic state. OBJECTIVE: To assess, using numerical and computational fluid dynamic analysis (CFD), the potential of cavitation to both induce damage to coronary artery endothelium and to promote atherosclerotic plaque progression. METHODS: We retrospectively reviewed the data 12 consecutive patients evaluated between 1st January 2013 and 1st January 2014 with an isolated hemodynamically significant Left Main (LM) disease. The patient specific geometries have been reconstructed. Bubble velocity has been calculated in accordance with Newton's second law. Both the forces arising from the bubbles' interaction with the continuous phase and impact with the endothelium have been evaluated. The impact of turbulence on the motion of bubbles have been modelled with a dispersion model. RESULTS: Among the 12 patients retrospectively analysed [8 males, mean age 68.2 ± 12.8 years old], the mean LM stenosis was 72.3 ± 3.6%. As expected, in all subjects, LM stenoses induced cavitation which propagates downstream the vessel creating microbubbles. The higher concentration of vapor region was detected before the carina (within 0.8 to 1.3 cm from the stenosis). Due to the pressure gradient generated by the stenosis, formation of a re-entry jet which penetrates each bubble generated a shock wave. Before the carina, the mean bubbles radius observed was 4.2 ± 1.4 µm, which generated a mean peak pressure of 3.9 ± 0.5 MPa when they explode. CONCLUSION: The cavitation phenomenon is effectively generated in a model of LM bifurcation and instantaneous pressure-peaks due to collapses of vapor bubbles resulted in a measurable dynamic load on vessel wall potentially able to induce endothelial damage.

Arbitrary access to optical carriers in silicon photonic mode/wavelength hybrid division multiplexing circuits.

The manipulation of optical modes directly in a multimode waveguide without affecting the transmission of undesired signal carriers is of significance to realize a flexible and simple structured optical network-on-chip. In this Letter, an arbitrary optical mode and wavelength carrier access scheme is proposed based on a series of multimode microring resonators and one multimode bus waveguide with constant width. As a proof-of-concept, a three-mode (de)multiplexing device is designed, fabricated, and experimentally demonstrated. A new, to the best of our knowledge, phase-matching idea is employed to keep the bus waveguide width constant. The mode coupling regions and transmission regions of the microring resonators are designed carefully to selectively couple and transmit different optical modes. The extinction ratio of the microring resonators is larger than 21.0 dB. The mode and wavelength cross-talk for directly (de)multiplexing are less than -12.8 dB and -19.0 dB, respectively. It would be a good candidate for future large-scale multidimensional optical networks.

Direct synthesis of Z-alkenyl halides through catalytic cross-metathesis.

Olefin metathesis has had a large impact on modern organic chemistry, but important shortcomings remain: for example, the lack of efficient processes that can be used to generate acyclic alkenyl halides. Halo-substituted ruthenium carbene complexes decompose rapidly or deliver low activity and/or minimal stereoselectivity, and our understanding of the corresponding high-oxidation-state systems is limited. Here we show that previously unknown halo-substituted molybdenum alkylidene species are exceptionally reactive and are able to participate in high-yielding olefin metathesis reactions that afford acyclic 1,2-disubstituted Z-alkenyl halides. Transformations are promoted by small amounts of a catalyst that is generated in situ and used with unpurified, commercially available and easy-to-handle liquid 1,2-dihaloethene reagents, and proceed to high conversion at ambient temperature within four hours. We obtain many alkenyl chlorides, bromides and fluorides in up to 91 per cent yield and complete Z selectivity. This method can be used to synthesize biologically active compounds readily and to perform site- and stereoselective fluorination of complex organic molecules.

A graph-based algorithm for detecting rigid domains in protein structures.

BACKGROUND: Conformational transitions are implicated in the biological function of many proteins. Structural changes in proteins can be described approximately as the relative movement of rigid domains against each other. Despite previous efforts, there is a need to develop new domain segmentation algorithms that are capable of analysing the entire structure database efficiently and do not require the choice of protein-dependent tuning parameters such as the number of rigid domains. RESULTS: We develop a graph-based method for detecting rigid domains in proteins. Structural information from multiple conformational states is represented by a graph whose nodes correspond to amino acids. Graph clustering algorithms allow us to reduce the graph and run the Viterbi algorithm on the associated line graph to obtain a segmentation of the input structures into rigid domains. In contrast to many alternative methods, our approach does not require knowledge about the number of rigid domains. Moreover, we identified default values for the algorithmic parameters that are suitable for a large number of conformational ensembles. We test our algorithm on examples from the DynDom database and illustrate our method on various challenging systems whose structural transitions have been studied extensively. CONCLUSIONS: The results strongly suggest that our graph-based algorithm forms a novel framework to characterize structural transitions in proteins via detecting their rigid domains. The web server is available at http://azifi.tz.agrar.uni-goettingen.de/webservice/ .

Ridge resonators: impact of excitation beam and resonator losses.

Photonic resonators based on bound states in the continuum are attractive for sensing and telecommunication applications, as they have the potential to achieve ultra-high Q-factor resonators in a compact footprint. Recently, ridge resonators - leaky mode resonators based on a bound state in the continuum - have been demonstrated on a scalable photonic integrated circuit platform. However, high Q-factor ridge resonators have thus far not been achieved. In this contribution, we investigate the influence of excitation beam width and optical losses on the spectral response of ridge resonators. We show that for practical applications, the space required of the excitation beam is the limiting factor on the highest achievable Q-factor.

Integrated photonic high extinction short and long pass filters based on lateral leakage.

In this contribution we present a new approach to achieve high extinction short and long pass wavelength filters in the integrated photonic platform of lithium niobate on insulator. The filtering of unwanted wavelengths is achieved by employing lateral leakage and is related to the bound state in the continuum phenomenon. We show that it is possible to control the filter edge wavelength by adjusting the waveguide dimensions and that an extinction of hundreds of dB/cm is readily achievable. This enabled us to design a pump wavelength suppression of more than 100 dB in a 3.5 mm long waveguide, which is essential for on-chip integration of quantum-correlated photon pair sources. These findings pave the way to integrate multi wavelength experiments on chip for the next generation of photonic integrated circuits.

High-speed electro-optic modulator based on silicon nitride loaded lithium niobate on an insulator platform.

Electro-optic (EO) modulators, which convert signals from the electrical to optical domain plays a key role in modern optical communication systems. Lithium niobate on insulator (LNOI) technology has emerged as a competitive solution to realize high-performance integrated EO modulators. In this Letter, we design and experimentally demonstrate a Mach-Zehnder interferometer-based modulator on a silicon nitride loaded LNOI platform, which not only takes full advantage of the excellent EO effect of LiNbO3, but also avoids the direct etching of LiNbO3 thin film. The measured half-wave voltage length product of the fabricated modulator is 2.24 V·cm, and the extinction ratio is ∼20dB. Moreover, the 3 dB EO bandwidth is ∼30GHz, while the modulated data rate for on-off key signals can reach up to 80 Gbps.

Cavitation in left ventricular assist device patients: a potential early sign of pump thrombosis.

Mechanical ventricular support with left ventricular assist device (LVAD) has emerged as a durable and safe therapy, both as bridge-to-transplant (BTT) or destination therapy (DT), in patients with advanced heart failure (HF). However, the occurrence of pump thrombosis (PT) still represents a serious complication, especially when LVADs of first or second generation are implanted. During the latest years, some investigations have recognized the occurrence of cavitation, evidenced through transthoracic echocardiography (TTE), as a potential early and indirect sign of PT. In the present manuscript, we reviewed the available data on the occurrence of cavitation in LVAD patients as an early potential marker of PT, also presenting the hemodynamic mechanisms involved.

On-chip switchable and reconfigurable optical mode exchange device using cascaded three-waveguide-coupling switches.

Data exchange between different data channels can offer more flexible and advanced functions for many optical networks. In this paper, we propose a switchable and reconfigurable data exchange device for arbitrary two optical mode channels based on three-waveguide-coupling (TWC) switches in mode-division multiplexing (MDM) networks. The working principle of the TWC switches is numerically analyzed using the coupled supermode theory. As a proof of concept, switchable data exchange between arbitrary two mode channels among the first three-order quasi-transverse electric modes is experimentally demonstrated successfully. The insertion losses of the device are less than 5.6 dB, including the coupling loss of the multiplexer and demultiplexer, while the mode crosstalk is less than -13.0 dB for all functions. The proposed device is expected to offer more flexibility to on-chip MDM networks due to its low loss, low crosstalk and good scalability.