Fumonisin B1 protects against long-chained polyunsaturated fatty acid-induced cell death in HepG2 cells - implications for cancer promotion.

Fumonisin B1 (FB1), a food-borne mycotoxin, is a cancer promoter in rodent liver and augments proliferation of initiated cells while inhibiting the growth of normal hepatocytes by disrupting lipid biosynthesis at various levels. HepG2 cancer cells exhibited resistance to FB1-induced toxic effects presumably due to their low content of polyunsaturated fatty acids (PUFA) even though FB1-typical lipid changes were observed, e.g. significantly increased phosphatidylethanolamine (PE), decreased sphingomyelin and cholesterol content, increased sphinganine (Sa) and sphinganine/sphingosine ratio, increased C18:1ω-9, decreased C20:4ω-6 content in PE and decreased C20:4ω-6_PC/PE ratio. Increasing PUFA content of HepG2 cells with phosphatidylcholine (PC) vesicles containing C20:4ω-6 (SAPC) or C22:6ω-3 (SDPC) disrupted cell survival, cellular redox status and induced oxidative stress and apoptosis. A partially protective effect of FB1 was evident in PUFA-enriched HepG2 cells which may be related to the FB1-induced reduction in oxidative stress and the disruption of key cell membrane constituents indicative of a resistant lipid phenotype. Interactions between different ω-6 and ω-3 PUFA, membrane constituents including cholesterol, and the glycerophospho- and sphingolipids and FB1 in this cell model provide further support for the resistant lipid phenotype and its role in the complex cellular effects underlying the cancer promoting potential of the fumonisins.

Signatures of enhanced out-of-plane polarization in asymmetric BaTiO3 superlattices integrated on silicon.

In order to bring the diverse functionalities of transition metal oxides into modern electronics, it is imperative to integrate oxide films with controllable properties onto the silicon platform. Here, we present asymmetric LaMnO3/BaTiO3/SrTiO3 superlattices fabricated on silicon with layer thickness control at the unit-cell level. By harnessing the coherent strain between the constituent layers, we overcome the biaxial thermal tension from silicon and stabilize c-axis oriented BaTiO3 layers with substantially enhanced tetragonality, as revealed by atomically resolved scanning transmission electron microscopy. Optical second harmonic generation measurements signify a predominant out-of-plane polarized state with strongly enhanced net polarization in the tricolor superlattices, as compared to the BaTiO3 single film and conventional BaTiO3/SrTiO3 superlattice grown on silicon. Meanwhile, this coherent strain in turn suppresses the magnetism of LaMnO3 as the thickness of BaTiO3 increases. Our study raises the prospect of designing artificial oxide superlattices on silicon with tailored functionalities.

Strain-Engineered Metal-to-Insulator Transition and Orbital Polarization in Nickelate Superlattices Integrated on Silicon.

Epitaxial growth of SrTiO3 (STO) on silicon greatly accelerates the monolithic integration of multifunctional oxides into the mainstream semiconductor electronics. However, oxide superlattices (SLs), the birthplace of many exciting discoveries, remain largely unexplored on silicon. In this work, LaNiO3 /LaFeO3 SLs are synthesized on STO-buffered silicon (Si/STO) and STO single-crystal substrates, and their electronic properties are compared using dc transport and X-ray absorption spectroscopy. Both sets of SLs show a similar thickness-driven metal-to-insulator transition, albeit with resistivity and transition temperature modified by the different amounts of strain. In particular, the large tensile strain promotes a pronounced Ni 3 d x 2 - y 2 orbital polarization for the SL grown on Si/STO, comparable to that reported for LaNiO3 SL epitaxially strained to DyScO3 substrate. Those results illustrate the ability to integrate oxide SLs on silicon with structure and property approaching their counterparts grown on STO single crystal, and also open up new prospects of strain engineering in functional oxides based on the Si platform.

Integration of Single Oriented Oxide Superlattices on Silicon Using Various Template Techniques.

To benefit from the diverse functionalities of perovskite oxides in silicon-based complementary metal oxide semiconductor (CMOS) technology, integrating oxides into a silicon platform has become one of the major tasks for oxide research. Using the deposition of LaMnO3/SrTiO3 (STO) superlattices (SLs) as a case study, we demonstrate that (001) single oriented oxide SLs can be integrated on Si using various template techniques, including a single-layer buffer of STO prepared by molecular beam epitaxy (MBE) and pulsed laser deposition, a multilayer buffer of Y-stabilized zirconia/CeO2/LaNiO3/STO, and STO-coated two-dimensional nanosheets of Ca2Nb3O10 (CNO) and reduced graphene oxide. The textured SL grown on STO-coated CNO nanosheets shows the highest crystallinity, owing to the small lattice mismatch between CNO and STO as well as less clamping from a Si substrate. The epitaxial SL grown on STO buffer prepared by MBE suffers the largest thermal strain, giving rise to a strongly suppressed saturation magnetization but an enhanced coercive field, as compared to the reference SL grown on an STO single crystal. These optional template techniques used for integrating oxides on Si are of significance to fulfill practical applications of oxide films in different fields.

An integrated optical modulator operating at cryogenic temperatures.

Photonic integrated circuits (PICs) operating at cryogenic temperatures are fundamental building blocks required to achieve scalable quantum computing and cryogenic computing technologies1,2. Silicon PICs have matured for room-temperature applications, but their cryogenic performance is limited by the absence of efficient low-temperature electro-optic modulation. Here we demonstrate electro-optic switching and modulation from room temperature down to 4 K by using the Pockels effect in integrated barium titanate (BaTiO3) devices3. We investigate the temperature dependence of the nonlinear optical properties of BaTiO3, showing an effective Pockels coefficient of 200 pm V-1 at 4 K. The fabricated devices show an electro-optic bandwidth of 30 GHz, ultralow-power tuning that is 109 times more efficient than thermal tuning, and high-speed data modulation at 20 Gbps. Our results demonstrate a missing component for cryogenic PICs, removing major roadblocks for the realization of cryogenic-compatible systems in the field of quantum computing, supercomputing and sensing, and for interfacing those systems with instrumentation at room temperature.

Neuromorphic Systems Design by Matching Inductive Biases to Hardware Constraints.

Neuromorphic systems are designed with careful consideration of the physical properties of the computational substrate they use. Neuromorphic engineers often exploit physical phenomena to directly implement a desired functionality, enabled by "the isomorphism between physical processes in different media" (Douglas et al., 1995). This bottom-up design methodology could be described as matching computational primitives to physical phenomena. In this paper, we propose a top-down counterpart to the bottom-up approach to neuromorphic design. Our top-down approach, termed "bias matching," is to match the inductive biases required in a learning system to the hardware constraints of its implementation; a well-known example is enforcing translation equivariance in a neural network by tying weights (replacing vector-matrix multiplications with convolutions), which reduces memory requirements. We give numerous examples from the literature and explain how they can be understood from this perspective. Furthermore, we propose novel network designs based on this approach in the context of collaborative filtering. Our simulation results underline our central conclusions: additional hardware constraints can improve the predictions of a Machine Learning system, and understanding the inductive biases that underlie these performance gains can be useful in finding applications for a given constraint.

Back-End, CMOS-Compatible Ferroelectric Field-Effect Transistor for Synaptic Weights.

Neuromorphic computing architectures enable the dense colocation of memory and processing elements within a single circuit. This colocation removes the communication bottleneck of transferring data between separate memory and computing units as in standard von Neuman architectures for data-critical applications including machine learning. The essential building blocks of neuromorphic systems are nonvolatile synaptic elements such as memristors. Key memristor properties include a suitable nonvolatile resistance range, continuous linear resistance modulation, and symmetric switching. In this work, we demonstrate voltage-controlled, symmetric and analog potentiation and depression of a ferroelectric Hf0.57Zr0.43O2 (HZO) field-effect transistor (FeFET) with good linearity. Our FeFET operates with low writing energy (fJ) and fast programming time (40 ns). Retention measurements have been performed over 4 bit depth with low noise (1%) in the tungsten oxide (WOx) readout channel. By adjusting the channel thickness from 15 to 8 nm, the on/off ratio of the FeFET can be engineered from 1 to 200% with an on-resistance ideally >100 kΩ, depending on the channel geometry. The device concept is using earth-abundant materials and is compatible with a back end of line (BEOL) integration into complementary metal-oxide-semiconductor (CMOS) processes. It has therefore a great potential for the fabrication of high-density, large-scale integrated arrays of artificial analog synapses.

Large Pockels effect in micro- and nanostructured barium titanate integrated on silicon.

The electro-optical Pockels effect is an essential nonlinear effect used in many applications. The ultrafast modulation of the refractive index is, for example, crucial to optical modulators in photonic circuits. Silicon has emerged as a platform for integrating such compact circuits, but a strong Pockels effect is not available on silicon platforms. Here, we demonstrate a large electro-optical response in silicon photonic devices using barium titanate. We verify the Pockels effect to be the physical origin of the response, with r42 = 923 pm V-1, by confirming key signatures of the Pockels effect in ferroelectrics: the electro-optic response exhibits a crystalline anisotropy, remains strong at high frequencies, and shows hysteresis on changing the electric field. We prove that the Pockels effect remains strong even in nanoscale devices, and show as a practical example data modulation up to 50 Gbit s-1. We foresee that our work will enable novel device concepts with an application area largely extending beyond communication technologies.

Microstructure and ferroelectricity of BaTiO3 thin films on Si for integrated photonics.

Significant progress has been made in integrating novel materials into silicon photonic structures in order to extend the functionality of photonic circuits. One of these promising optical materials is BaTiO3 or barium titanate (BTO) that exhibits a very large Pockels coefficient as required for high-speed light modulators. However, all previous demonstrations show a noticable reduction of the Pockels effect in BTO thin films deposited on silicon substrates compared to BTO bulk crystals. Here, we report on the strong dependence of the Pockels effect in BTO thin films on their microstructure, and provide guidelines on how to engineer thin films with strong electro-optic response. We employ several deposition methods such as molecular beam epitaxy and chemical vapor deposition to realize BTO thin films with different morphology and crystalline structure. While a linear electro-optic response is present even in porous, polycrystalline BTO thin films with an effective Pockels coefficient r eff = 6 pm V-1, it is maximized for dense, tetragonal, epitaxial BTO films (r eff = 140 pm V-1). By identifying the key structural predictors of electro-optic response in BTO/Si, we provide a roadmap to fully exploit the linear electro-optic effect in novel hybrid oxide/semiconductor nanophotonic devices.

Monolithically Integrated Microelectromechanical Systems for On-Chip Strain Engineering of Quantum Dots.

Elastic strain fields based on single crystal piezoelectric elements represent an effective way for engineering the quantum dot (QD) emission with unrivaled precision and technological relevance. However, pioneering researches in this direction were mainly based on bulk piezoelectric substrates, which prevent the development of chip-scale devices. Here, we present a monolithically integrated Microelectromechanical systems (MEMS) device with great potential for on-chip quantum photonic applications. High-quality epitaxial PMN-PT thin films have been grown on SrTiO3 buffered Si and show excellent piezoelectric responses. Dense arrays of MEMS with small footprints are then fabricated based on these films, forming an on-chip strain tuning platform. After transferring the QD-containing nanomembranes onto these MEMS, the nonclassical emissions (e.g., single photons) from single QDs can be engineered by the strain fields. We envision that the strain tunable QD sources on the individually addressable and monolithically integrated MEMS pave the way toward complex quantum photonic applications on chip.

Species-wide genome sequence and nucleotide polymorphisms from the model allopolyploid plant Brassica napus.

Brassica napus (oilseed rape, canola) is one of the world's most important sources of vegetable oil for human nutrition and biofuel, and also a model species for studies investigating the evolutionary consequences of polyploidisation. Strong bottlenecks during its recent origin from interspecific hybridisation, and subsequently through intensive artificial selection, have severely depleted the genetic diversity available for breeding. On the other hand, high-throughput genome profiling technologies today provide unprecedented scope to identify, characterise and utilise genetic diversity in primary and secondary crop gene pools. Such methods also enable implementation of genomic selection strategies to accelerate breeding progress. The key prerequisite is availability of high-quality sequence data and identification of high-quality, genome-wide sequence polymorphisms representing relevant gene pools. We present comprehensive genome resequencing data from a panel of 52 highly diverse natural and synthetic B. napus accessions, along with a stringently selected panel of 4.3 million high-confidence, genome-wide SNPs. The data is of great interest for genomics-assisted breeding and for evolutionary studies on the origins and consequences in allopolyploidisation in plants.

A strong electro-optically active lead-free ferroelectric integrated on silicon.

The development of silicon photonics could greatly benefit from the linear electro-optical properties, absent in bulk silicon, of ferroelectric oxides, as a novel way to seamlessly connect the electrical and optical domain. Of all oxides, barium titanate exhibits one of the largest linear electro-optical coefficients, which has however not yet been explored for thin films on silicon. Here we report on the electro-optical properties of thin barium titanate films epitaxially grown on silicon substrates. We extract a large effective Pockels coefficient of r(eff) = 148 pm V(-1), which is five times larger than in the current standard material for electro-optical devices, lithium niobate. We also reveal the tensor nature of the electro-optical properties, as necessary for properly designing future devices, and furthermore unambiguously demonstrate the presence of ferroelectricity. The integration of electro-optical active films on silicon could pave the way towards power-efficient, ultra-compact integrated devices, such as modulators, tuning elements and bistable switches.

Peripheral blood mononuclear cell membrane fluidity and disease outcome in patients with multiple sclerosis.

Immune cell membrane lipids are important determinants of membrane fluidity, eicosanoid production and phagocytosis and fatty acid metabolic abnormalities have been reported in immune cells from patients with multiple sclerosis. The aim of this study was to investigate the relationship between peripheral blood mononuclear cell membrane fluidity, permeability status, and disease outcome as measured by the Kurtzke expanded disability status scale. Phospholipids, fatty acids and cholesterol composition in peripheral blood mononuclear cells from 26 patients diagnosed with multiple sclerosis and 25 healthy control subjects were determined by colorimetric assay, gas chromatography and enzymatic assays, respectively. Membrane fluidity was calculated according to previously established formulae and correlated with C-reactive protein and the Kurtzke expanded disability status scale. There were no significant differences in membrane lipids in peripheral blood mononuclear cells from patients and controls. However, correlation studies showed lipid metabolic abnormalities, which were reflected in significant correlations between membrane fluidity as measured by both its fatty acid and phospholipid compositions, and the functional system scores. C-reactive protein showed positive correlations with phosphatidylcholine, phosphatidylserine, phosphatidylinositol and total phospholipids in membranes from control subjects. Metabolic abnormalities, as well as correlations between membrane fluidity and the functional system scores, suggested the involvement of these immune cell membranes in the disease progression. Furthermore, the changed relationship between membrane phospholipids and C-reactive protein, which has been shown to correlate with infectious episodes and clinical relapse, could be an indication of immune cell dysfunction in patients with multiple sclerosis.

Dissecting the genetic architecture of agronomic traits in multiple segregating populations in rapeseed (Brassica napus L.).

Detection of QTL in multiple segregating populations is of high interest as it includes more alleles than mapping in a single biparental population. In addition, such populations are routinely generated in applied plant breeding programs and can thus be used to identify QTL which are of direct relevance for a marker-assisted improvement of elite germplasm. Multiple-line cross QTL mapping and joint linkage association mapping were used for QTL detection. We empirically compared these two different biometrical approaches with regard to QTL detection for important agronomic traits in nine segregating populations of elite rapeseed lines. The plants were intensively phenotyped in multi-location field trials and genotyped with 253 SNP markers. Both approaches detected several additive QTL for diverse traits, including flowering time, plant height, protein content, oil content, glucosinolate content, and grain yield. In addition, we identified one epistatic QTL for flowering time. Consequently, both approaches appear suited for QTL detection in multiple segregating populations.

Monounsaturated fatty acids in blood cell membranes from patients with multiple sclerosis.

The aim of this study was to investigate whether blood cell membrane monounsaturated fatty acids were associated with inflammation and disease outcome in patients with multiple sclerosis. The fatty acid composition in peripheral blood mononuclear cell and red blood cell membranes from 26 patients and 25 controls were determined by gas chromatography. Results showed positive associations between C-reactive protein and C16:1n-7, C18:1n-7, and C24:1n-9 in membranes from controls only. In general, C18:1n-9 and C20:1n-9 showed inverse correlations, while C16:1n-7 and C18:1n-7 showed positive correlations with disease outcome. Multiple sclerosis has a known inflammatory component. There is scarcity of literature on the role of monounsaturated fatty acids in inflammation, but results from this study suggested an association in healthy subjects between monounsaturated fatty acids and C-reactive protein, even at physiologically low levels. This association was not found in the plasma from patients. Furthermore, the n-9 and n-7 fatty acids played different roles in disease outcome, and therefore warrant inclusion, together with polyunsaturated fatty acids when investigating the inflammatory aspects of the disease.

Red blood cell membrane fluidity in the etiology of multiple sclerosis.

Organisms adjust the order, or fluidity, of their cellular membranes in response to changes in their physiochemical environment by adjusting the lipid composition of their membranes. We investigated membrane fluidity using the phospholipid, fatty acid and cholesterol content of red blood cells (RBCs) from multiple sclerosis (MS) patients and correlated this with C-reactive protein (CRP) as well as with the severity of neurological outcome as measured by the Kurtzke Expanded Disability Status Scale (EDSS) and its Functional System Scores. The study group consisted of 31 patients with MS and 30 healthy control subjects. Phospholipids were determined using a colorimetric assay, fatty acids by gas chromatography, cholesterol by an enzymatic assay and CRP by a Beckman nephelometer. Cell membrane fluidity was calculated according to previously established formulae. RBC membrane fluidity as measured by the saturated to polyunsaturated fatty acid ratio was higher in patients than in controls (P = 0.04). The phosphatidylethanolamine saturated to polyunsaturated fatty acid ratio showed highly significant positive correlations with the EDSS and CRP < 5 microg/ml. CRP showed significant inverse correlations with the saturated nature but positive correlations with the ordered-crystalline-phase to liquid-crystalline-phase lipid ratio. In this study we show that membrane fluidity as measured by the relationship between membrane fatty acids, phospholipids and cholesterol is closely interrelated with inflammation and disease outcome in patients with MS. In conclusion, our findings suggest that the membrane lipid composition of patients with MS and, consequently, membrane fluidity are altered, which seems to be influenced by the inflammatory status.

Immune cell membrane fatty acids and inflammatory marker, C-reactive protein, in patients with multiple sclerosis.

Measurement of fatty acids in biological fluids and cell membranes including leucocytes from multiple sclerosis patients is inconsistent. The objective of the present study was to investigate the fatty acid composition within the different membrane phospholipid fractions in peripheral blood mononuclear cells in multiple sclerosis patients, and correlate with severity of neurological outcome as measured by the Kurtzke Expanded Disability Status Scale and Functional System Scores. The fatty acid composition of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin and phosphatidylinositol phospholipids in the peripheral blood mononuclear cells of twenty-six multiple sclerosis and twenty-five control subjects were measured by GC, and C-reactive protein was measured in all subjects. The elongation product of 20 : 4n-6, 22 : 4n-6, was significantly decreased in membrane phosphatidylethanolamine and phosphatidylserine in multiple sclerosis patients (P = 0.01 and P = 0.03 respectively), and correlated inversely with severity of disease and C-reactive protein. Also an inverse correlation was observed between the C-reactive protein and membrane phosphatidylcholine and phosphatidylserine 20 : 4n-6. Cultural and ethnic differences, as well as dietary variability, especially in a diseased state have been implicated in the differences observed in the fatty acid composition in peripheral blood mononuclear cell membranes of patients with multiple sclerosis. The present results suggest that the disease state may in part explain the reported inconsistencies in fatty acid levels in multiple sclerosis patients.