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Nonlinear optical and electrical effects associated with a lack of spatial inversion symmetry allow direction-selective propagation and transport of quantum particles, such as photons1 and electrons2-9. The most common example of such nonreciprocal phenomena is a semiconductor diode with a p-n junction, with a low resistance in one direction and a high resistance in the other. Although the diode effect forms the basis of numerous electronic components, such as rectifiers, alternating-direct-current converters and photodetectors, it introduces an inevitable energy loss due to the finite resistance. Therefore, a worthwhile goal is to realize a superconducting diode that has zero resistance in only one direction. Here we demonstrate a magnetically controllable superconducting diode in an artificial superlattice [Nb/V/Ta]n without a centre of inversion. The nonreciprocal resistance versus current curve at the superconducting-to-normal transition was clearly observed by a direct-current measurement, and the difference of the critical current is considered to be related to the magnetochiral anisotropy caused by breaking of the spatial-inversion and time-reversal symmetries10-13. Owing to the nonreciprocal critical current, the [Nb/V/Ta]n superlattice exhibits zero resistance in only one direction. This superconducting diode effect enables phase-coherent and direction-selective charge transport, paving the way for the construction of non-dissipative electronic circuits.
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The acetal (O-glycoside) bonds of glycans and glycoconjugates are chemically and biologically vulnerable, and therefore C-glycosides are of interest as more stable analogs. We hypothesized that, if the O-glycoside linkage plays a vital role in glycan function, the biological activities of C-glycoside analogs would vary depending on their substituents. Based on this idea, we adopted a "linkage-editing strategy" for the creation of glycan analogs (pseudo-glycans). We designed three types of pseudo-glycans with CH2 and CHF linkages, which resemble the O-glycoside linkage in terms of bond lengths, angles, and bulkiness, and synthesized them efficiently by means of fluorovinyl C-glycosylation and selective hydrogenation reactions. Application of this strategy to isomaltose (IM), an inducer of amylase expression, and α-GalCer, which activates iNKT cells, resulted in the discovery of CH2-IM, which shows increased amylase production ability, and CHF-α-GalCer, which shows activity opposite that of native α-GalCer, serving as an antagonist of iNKT cells.
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Galactosilceramidas , Glicósidos , Polisacáridos , Glicosilación , Polisacáridos/química , Amilasas/metabolismoRESUMEN
Melibiosamine (Gal-α(1,6)-GlcNH2), consisting of galactose and glucosamine linked by an α(1,6)-glycosidic bond, is an artificial disaccharide derivative that selectively inhibits the proliferation of K562 tumor cells relative to HUC-F2 normal cells. In this study, we employed a linkage-editing strategy to synthesize CH2- and CHF-linked melibiosamine analogs through chemo- and stereoselective hydrogenation of fluorovinyl-C-glycoside. (R)-CHF-Melibiosamine exhibited more potent antiproliferative activity than O-linked melibiosamine, while (S)-CHF-melibiosamine was less potent.
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Proliferación Celular , Humanos , Células K562 , Proliferación Celular/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Glucosamina/química , Disacáridos/química , Disacáridos/síntesis química , Disacáridos/farmacología , Estereoisomerismo , Estructura Molecular , Galactosa/química , Ensayos de Selección de Medicamentos Antitumorales , Relación Estructura-ActividadRESUMEN
Minimalist photo-reactive probes, which consist of a photo-reactive group and a tag for detection of target proteins, are useful tools in chemical biology. Although several diazirine-based and aryl azide-based minimalist probes are available, no keto-based minimalist probe has yet been reported. Here we describe minimalist probes based on a 2-thienyl-substituted α-ketoamide bearing an alkyne group on the thiophene ring. The 3-alkyne probe showed the highest photo-affinity labeling efficiency.
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Azidas , Etiquetas de Fotoafinidad , Marcadores de Afinidad , Alquinos , Etiquetas de Fotoafinidad/metabolismo , ProteínasRESUMEN
Symmetry breaking is a fundamental concept that prevails in many branches of physics1-5. In magnetic materials, broken inversion symmetry induces the Dzyaloshinskii-Moriya interaction (DMI), which results in fascinating physical behaviours6-14 with the potential for application in future spintronic devices15-17. Here, we report the observation of a bulk DMI in GdFeCo amorphous ferrimagnets. The DMI is found to increase linearly with an increasing thickness of the ferrimagnetic layer, which is a clear signature of the bulk nature of DMI. We also found that the DMI is independent of the interface between the heavy metal and ferrimagnetic layer. This bulk DMI is attributed to an asymmetric distribution of the elemental content in the GdFeCo layer, with spatial inversion symmetry broken throughout the layer. We expect that our experimental identification of a bulk DMI will open up additional possibilities to exploit this interaction in a wide range of materials.
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We report an experimental observation of magnon-magnon coupling in interlayer exchange coupled synthetic antiferromagnets of FeCoB/Ru/FeCoB layers. An anticrossing gap of spin-wave resonance between acoustic and optic modes appears when the external magnetic field points to the direction tilted from the spin-wave propagation. The magnitude of the gap (i.e., coupling strength) can be controlled by changing the direction of the in-plane magnetic field and also enhanced by increasing the wave number of excited spin waves. We find that the coupling strength under the specified conditions is larger than the dissipation rates of both the resonance modes, indicating that a strong coupling regime is satisfied. A theoretical analysis based on the Landau-Lifshitz equation shows quantitative agreement with the experiments and indicates that the anticrossing gap appears when the exchange symmetry of two magnetizations is broken by the spin-wave excitation.
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We investigate the Gilbert damping parameter α for rare earth (RE)-transition metal (TM) ferrimagnets over a wide temperature range. Extracted from the field-driven magnetic domain-wall mobility, α was as low as the order of 10^{-3} and was almost constant across the angular momentum compensation temperature T_{A}, starkly contrasting previous predictions that α should diverge at T_{A} due to a vanishing total angular momentum. Thus, magnetic damping of RE-TM ferrimagnets is not related to the total angular momentum but is dominated by electron scattering at the Fermi level where the TM has a dominant damping role. This low value of the Gilbert damping parameter suggests that ferrimagnets can serve as versatile platforms for low-dissipation high-speed magnetic devices.
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Antiferromagnetic spintronics is an emerging research field which aims to utilize antiferromagnets as core elements in spintronic devices. A central motivation towards this direction is that antiferromagnetic spin dynamics is expected to be much faster than its ferromagnetic counterpart. Recent theories indeed predicted faster dynamics of antiferromagnetic domain walls (DWs) than ferromagnetic DWs. However, experimental investigations of antiferromagnetic spin dynamics have remained unexplored, mainly because of the magnetic field immunity of antiferromagnets. Here we show that fast field-driven antiferromagnetic spin dynamics is realized in ferrimagnets at the angular momentum compensation point TA. Using rare earth-3d-transition metal ferrimagnetic compounds where net magnetic moment is nonzero at TA, the field-driven DW mobility is remarkably enhanced up to 20 km s-1 T-1. The collective coordinate approach generalized for ferrimagnets and atomistic spin model simulations show that this remarkable enhancement is a consequence of antiferromagnetic spin dynamics at TA. Our finding allows us to investigate the physics of antiferromagnetic spin dynamics and highlights the importance of tuning of the angular momentum compensation point of ferrimagnets, which could be a key towards ferrimagnetic spintronics.
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In this Letter, we show the demonstration of a sequential antiferromagnetic memory operation with a spin-orbit-torque write, by the spin Hall effect, and a resistive read in the CoGd synthetic antiferromagnetic bits, in which we reveal the distinct differences in the spin-orbit-torque and field-induced switching mechanisms of the antiferromagnetic moment, or the Néel vector. In addition to the comprehensive spin torque memory operation, our thorough investigations also highlight the high immunity to a field disturbance as well as a memristive behavior of the antiferromagnetic bits.
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Spin interaction in antiferromagnetic materials is of central interest in the recently emerging antiferromagnetic spintronics. In this Letter, we explore the spin current interaction in antiferromagnetic FeMn by the spin pumping effect. Exchange biased FeNi/FeMn films, in which the Néel vector can be presumably controlled via the exchange spring effect, are employed to investigate the damping enhancement depending on the relative orientation between the Néel vector and the polarization of the pumped spin current. The correlation between the enhanced damping and the strength of the exchange bias suggests that the twisting of the Néel vector induces an additional spin dissipation, which verifies that the Slonczewski-type spin torque is effective even in antiferromagnetic materials.
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PURPOSE: Acute kidney injury (AKI) is one of the critical complications after cardiac surgery. In the kidney, angiotensin II (Ang II) is formed by independent mechanisms, and activity of the intrarenal renin-angiotensin-aldosterone (RAAS) system contributes to the progression of kidney damage. Although atrial natriuretic peptide (ANP) exerts protective effects against renal injury by inhibiting the RAAS, the mechanisms of this effect have not been completely clarified. We investigated how human ANP (hANP) could prevent renal damage induced by cardiopulmonary bypass. METHODS: Forty-eight patients undergoing cardiac surgery were divided into two groups, with and without hANP infusion. Urinary angiotensinogen, neutrophil gelatinase-associated lipocalin (NGAL) and L-type fatty acid-binding protein (L-FABP) were measured during and after surgery in both groups. Plasma renin activity, Ang II, aldosterone and serum creatinine were also measured. RESULTS: Urinary angiotensinogen levels in the hANP group were significantly lower than in the non-hANP group after cardiopulmonary bypass surgery, at the end of surgery and 3 h after surgery. At 3 h after surgery, urinary NGAL levels in the hANP and non-hANP groups were 371.1 ± 413.6 and 761.4 ± 437.8 µg/gCr, respectively (p < 0.01). Urinary L-FABP levels at the end of surgery in the hANP and non-hANP groups were 238.8 ± 107.4 and 573.9 ± 370.1 µg/gCr, respectively (p < 0.01). Moreover, hANP seemed to significantly reduce the incidence of postoperative AKI. CONCLUSIONS: hANP demonstrated renal protective effects during cardiac surgery, and could possibly reduce the incidence of AKI after ischemia-reperfusion surgery. Moreover, this protective effect of hANP is likely induced by inhibition of the intrarenal RAAS.
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Lesión Renal Aguda/prevención & control , Factor Natriurético Atrial/farmacología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Anciano , Angiotensina II/sangre , Puente Cardiopulmonar/efectos adversos , Proteínas de Unión a Ácidos Grasos/orina , Femenino , Humanos , Riñón/efectos de los fármacos , Masculino , Persona de Mediana Edad , Periodo PosoperatorioAsunto(s)
Intubación Intratraqueal/métodos , Síndrome de Klippel-Trenaunay-Weber/diagnóstico por imagen , Tráquea/irrigación sanguínea , Tráquea/diagnóstico por imagen , Várices/diagnóstico por imagen , Adulto , Cesárea/métodos , Femenino , Humanos , Síndrome de Klippel-Trenaunay-Weber/cirugía , EmbarazoRESUMEN
BACKGROUND: Ischemia-reperfusion (I/R) injury is one of the most important pathologic processes causing acute kidney injury. Human atrial natriuretic peptide (hANP) has various effects, including renal protection. The purpose of the present work was to study the effects of intrarenal angiotensin II (Ang II) and investigate the potential of hANP to prevent kidney injury. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into three groups as follows: (1) sham; (2) I/R (30 min of bilateral renal ischemia followed by 6 h reperfusion); and (3) I/R + hANP (I/R injury + continuous intravenous infusion of hANP at 0.025 µg/kg/min). After 6 h of reperfusion, both renal and plasma Ang II concentrations were measured. Urinary angiotensinogen and neutrophil gelatinase-associated lipocalin were measured before ischemia and 2, 4, and 6 h after reperfusion. To evaluate the renal-protective effects of hANP, serum creatinine was determined 6 and 24 h after reperfusion. In addition, mitochondrial oxygen consumption in kidney cortex was measured in the presence of Ang II and hANP. RESULTS: Renal Ang II concentrations were 24.5 ± 3.9 and 14.2 ± 3.4 pg/mg renal weight in the I/R and I/R + hANP groups, respectively. Urinary angiotensinogen and neutrophil gelatinase-associated lipocalin excretions were elevated after I/R injury. Treatment with hANP significantly attenuated this effect after 4 and 6 h. Oxygen consumption in renal mitochondria increased with the addition of Ang II, which was also attenuated by hANP. CONCLUSIONS: Production of intrarenal Ang II was attenuated by hANP, indicating a potential to diminish renal I/R injury.
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Lesión Renal Aguda/prevención & control , Angiotensina II/metabolismo , Factor Natriurético Atrial/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Daño por Reperfusión/prevención & control , Lesión Renal Aguda/metabolismo , Proteínas de Fase Aguda/orina , Angiotensinógeno/orina , Animales , Riñón/metabolismo , Lipocalina 2 , Lipocalinas/orina , Masculino , Mitocondrias/metabolismo , Consumo de Oxígeno , Complicaciones Posoperatorias/metabolismo , Proteínas Proto-Oncogénicas/orina , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismoRESUMEN
BACKGROUND: Rocuronium bromide (Rb) is a rapid onset, intermediate-acting neuromuscular blocking agent that is suitable for continuous administration. The appropriate rate of rocuronium administration is, however, difficult to determine due to large interindividual differences in sensitivity to rocuronium. The aim of this study was to clarify whether the simulated rocuronium concentration at the time of recovery to %T1 > 0 % after the initial administration of rocuronium is a good indicator of optimal effect-site concentrations during continuous rocuronium administration. METHODS: Twenty-one patients were anesthetized with propofol. After induction, Rb 0.6 mg/kg was administered intravenously, and nerve stimulation using the single stimulation mode was conducted every 15 s. When %T1 recovered to >0 % after the initial administration of Rb, the effect-site concentration of rocuronium, calculated by pharmacokinetic simulation with Wierda's set of parameters, was recorded and defined as the recovery concentration (Rb r.c.). The administration rate of rocuronium was adjusted to maintain the Rb r.c. during surgery. Rb administration was discontinued just before the end of surgery, and the recovery time until %T1 > 25 % was recorded. Plasma Rb concentrations were measured at 1 and 3 h after the initiation of continuous Rb administration. RESULT: The mean Rb r.c. was 1.56 ± 0.35 µg/ml, with minimum and maximum values of 1.09 and 2.08 µg/ml, respectively. The %T1 did not increase above 10 % in any of the patients during continuous administration of Rb, and the recovery period to %T1 > 25 % ranged from 9 to 29 min. The effect-site concentrations of Rb calculated with Wierda's parameters significantly correlated with plasma concentrations (P < 0.01) at both 1 and 3 h after the initial administration of Rb. CONCLUSION: The results suggest that our method may be one of the most reliable protocols for the continuous administration of Rb described to date for maintaining suitable muscle relaxation during surgery without excessively prolonged effects.
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Androstanoles/administración & dosificación , Fármacos Neuromusculares no Despolarizantes/administración & dosificación , Piperidinas/administración & dosificación , Propofol/administración & dosificación , Adulto , Anciano , Anestesia/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Relajación Muscular/efectos de los fármacos , Remifentanilo , RocuronioRESUMEN
The ability to drive a spin system to state far from the equilibrium is indispensable for investigating spin structures of antiferromagnets and their functional nonlinearities for spintronics. While optical methods have been considered for spin excitation, terahertz (THz) pulses appear to be a more convenient means of direct spin excitation without requiring coupling between spins and orbitals or phonons. However, room-temperature responses are usually limited to small deviations from the equilibrium state because of the relatively weak THz magnetic fields in common approaches. Here, we studied the magnetization dynamics in a HoFeO3 crystal at room temperature. A custom-made spiral-shaped microstructure was used to locally generate a strong multicycle THz magnetic near field perpendicular to the crystal surface; the maximum magnetic field amplitude of about 2 T was achieved. The observed time-resolved change in the Faraday ellipticity clearly showed second- and third-order harmonics of the magnetization oscillation and an asymmetric oscillation behaviour. Not only the ferromagnetic vector M but also the antiferromagnetic vector L plays an important role in the nonlinear dynamics of spin systems far from equilibrium.
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INTRODUCTION: Neuropathic pain remains one of the most intractable types of pain; although calcium channel α2δ ligands, such as pregabalin and gabapentin, are classified as first-line drugs, they have only modest efficacy. Heme oxygenase-1 (HO-1) signaling attenuates glial activation during neuropathic pain. Thus, this study aimed to investigate the effects of the blood-brain barrier (BBB)-permeable HO-1 inhibitor, tin protoporphyrin IX (SnPP), or the BBB-impermeable HO-1 inhibitor, zinc (II) protoporphyrin IX (ZnPP), on the analgesic efficacy of pregabalin and gabapentin. Additionally, we examined the effects of co-administration of SnPP with pregabalin or gabapentin on the expression of glial markers or other genes. METHODS: Neuropathic pain was induced by spared nerve injury (SNI) of the sciatic nerve. The mechanical threshold was tested using the von Frey filaments. The expression of spinal glial markers or other genes was examined using reverse transcription polymerase chain reaction. RESULTS: Systemic HO-1 inhibition reversed the mechanical antiallodynic effects of pregabalin and gabapentin, although peripheral HO-1 inhibition did not alter the mechanical antiallodynic effects of either pregabalin or gabapentin. Intrathecal injection of SnPP or ZnPP abolished the mechanical antiallodynic effects of pregabalin and gabapentin. Pregabalin and gabapentin increased HO-1, arginase-1, and endogenous opioid precursor preproenkephalin gene expression and decreased the expression of glial markers, interleukin-1ß, and inducible nitric oxide synthase. CONCLUSIONS: This study suggests that spinal HO-1 plays a crucial role in the analgesic effects of calcium channel α2δ ligands through the attenuation of glial activation and endogenous opioid release.
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Analgésicos/farmacología , Gabapentina/farmacología , Hemo-Oxigenasa 1/metabolismo , Neuralgia/metabolismo , Pregabalina/farmacología , Médula Espinal/metabolismo , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Nervio Ciático/lesionesRESUMEN
Pollen-free varieties are advantageous in promoting cut-flower production. In this study, we identified a candidate mutation which is responsible for pollen sterility in a strain of Lilium × formolongi, which was originally identified as a naturally occurred male-sterile plant in a seedling population. The pollen sterility occurred due to the degradation of pollen mother cells (PMCs) before meiotic cell division. Genetic analysis suggested that the male-sterile phenotype is attributed to one recessive locus. Transcriptome comparison between anthers of sterile and fertile plants in a segregated population identified a transcript that was expressed only in pollen-fertile plants, which is homologous to TDF1 (DEFECTIVE in TAPETAL DEVELOPMENT and FUNCTION1) in Arabidopsis, a gene encoding a transcription factor AtMYB35 that is known as a key regulator of pollen development. Since tdf1 mutant shows male sterility, we assumed that the absence transcript of the TDF1-like gene, named as LflTDF1, is the reason for pollen sterility observed in the mutant. A 30 kbp-long nanopore sequence read containing LflTDF1 was obtained from a pollen-fertile accession. PCR analyses using primers designed from the sequence suggested that at least a 30kbp-long region containing LflTDF1 was deleted or replaced by unknown sequence in the pollen-sterile mutant. Since the cross between L. × formolongi and Easter lily (L. longiflorum) is compatible, we successfully introgressed the male-sterile allele, designated as lfltdf1, to Easter lily. To our knowledge, this is the first report of molecular identification of a pollen-sterile candidate gene in lily. The identification and marker development of LflTDF1 gene will assist pollen-free lily breeding of Easter lilies and other lilies.
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Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cell carcinoma. Although usually indolent, high-grade MTSCC has been reported to exhibit an aggressive clinical course. Herein, we report a case of high-grade renal MTSCC. An 86-year-old man visited our hospital with fever and fatigue. Based on contrast-enhanced computed tomography findings, the patient was diagnosed with clinical stage T2aN0M0 right renal cell carcinoma and underwent laparoscopic radical nephrectomy. Histological examination showed tubular to tubulopapillary structures accompanied by mucinous stroma, suggesting high-grade renal MTSCC. He remained recurrence- and metastasis-free 6 months after nephrectomy. Since high-grade renal MTSCC may have an aggressive clinical course, such patients should be observed carefully after radical nephrectomy.
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The micropapillary variant of urothelial carcinoma (MPUC) is an aggressive form of urothelial carcinoma with high metastatic potential and a poor prognosis. Although various therapies have been reported, there is still no established treatment strategy for MPUC due to its rarity. The incidence of urinary tract malignancies is higher in patients undergoing hemodialysis (HD) than in healthy individuals. Here, we report the case of an 82-year-old man on HD with end-stage kidney disease who visited our hospital for macrohematuria. Cystoscopy followed by computed tomography and urine cytology revealed a sessile papillary tumor around the left bladder wall. We performed transurethral resection of the bladder tumor. Based on histopathological and imaging findings indicative of clinical-stage T3N0M0 MPUC, we performed radical cystectomy. Histopathology revealed a pathological stage T4aN0M0 MPUC. Two months after the cystectomy, the patient complained of constipation and painful defecation due to local recurrence and rectal invasion. While colostomy was performed to improve defecation 3 months after cystectomy, he did not receive any chemotherapy due to his progressively worsening general condition. Six months after cystectomy, he died following rapid metastases. Our findings, in this case, confirm that bladder cancer in HD patients tends to be pathologically more advanced. Therefore, regular screening is recommended for its early detection in HD patients.
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The diode effect is fundamental to electronic devices and is widely used in rectifiers and a.c.-d.c. converters. At low temperatures, however, conventional semiconductor diodes possess a high resistivity, which yields energy loss and heating during operation. The superconducting diode effect (SDE)1-8, which relies on broken inversion symmetry in a superconductor, may mitigate this obstacle: in one direction, a zero-resistance supercurrent can flow through the diode, but for the opposite direction of current flow, the device enters the normal state with ohmic resistance. The application of a magnetic field can induce SDE in Nb/V/Ta superlattices with a polar structure1,2, in superconducting devices with asymmetric patterning of pinning centres9 or in superconductor/ferromagnet hybrid devices with induced vortices10,11. The need for an external magnetic field limits their practical application. Recently, a field-free SDE was observed in a NbSe2/Nb3Br8/NbSe2 junction; it originates from asymmetric Josephson tunnelling that is induced by the Nb3Br8 barrier and the associated NbSe2/Nb3Br8 interfaces12. Here, we present another implementation of zero-field SDE using noncentrosymmetric [Nb/V/Co/V/Ta]20 multilayers. The magnetic layers provide the necessary symmetry breaking, and we can tune the SDE by adjusting the structural parameters, such as the constituent elements, film thickness, stacking order and number of repetitions. We control the polarity of the SDE through the magnetization direction of the ferromagnetic layers. Artificially stacked structures13-18, such as the one used in this work, are of particular interest as they are compatible with microfabrication techniques and can be integrated with devices such as Josephson junctions19-22. Energy-loss-free SDEs as presented in this work may therefore enable novel non-volatile memories and logic circuits with ultralow power consumption.