Tailored electrical characteristics in multilayer metal-oxide-based-memristive devices

Auf Mehrlagen-Metalloxiden basierende memristive Bauelemente sind einer der vielversprechendsten Kandidaten für neuromorphes Computing. Allerdings stellen spezifische Anwendungen des neuromorphen Computings unterschiedliche Anforderungen an die memristiven Bauelemente. Eine ungelöste Herausforderung in der technologischen Entwicklung ist daher das maßgeschneiderte Design von memristiven Bauelementen für spezifische Anwendungen. Insbesondere die unterschiedlichen Materialien des Schichtstapels erschweren die Herstellungsprozesse aufgrund einer großen Anzahl von Parametern, wie z. B. der Stapelsequenzen und -dicken und der Qualität sowie der Eigenschaften der einzelnen Schichten. Daher sind systematische Untersuchungen der einzelnen Bauelementparameter besonders entscheidend. Darüber hinaus müssen sie mit einem tiefgreifenden Verständnis der zugrundeliegenden physikalischen Prozesse kombiniert werden, um die Lücke zwischen Materialdesign und elektrischen Eigenschaften der resultierenden memristiven Bauelemente zuschließen. Um memristive Bauelemente mit unterschiedlichen resistiven Schalteigenschaften zu erhalten, werden verschiedene Abfolgen und Kombinationen von drei Metalloxidschichten (TiOx, HfOx, und AlOx) hergestellt und untersucht. Zunächst werden einschichtige Oxidbauelemente untersucht, um Kandidaten für mehrschichtige Stapel zu identifizieren. Zweitens werden zweischichtige TiOx/HfOx Oxidbauelemente hergestellt. Anhand von systematischen Experimenten und statistischen Analysen wird gezeigt, dass die Stöchiometrie, die Dicke, und die Fläche des Bauelements die Betriebsspannungen, die Nichtlinearität beim resistiven Schalten und die Variabilität beeinflussen. Drittens werden TiOx/AlOx/HfOx-basierte Bauelemente hergestellt. Durch das Hinzufügen von AlOx in die zweischichtigen Oxidstapel weisen diese dreischichtigen Bauelemente optimale elektrische Eigenschaften für den Einsatz in neuromorpher Hardware auf, wie z. B. elektroformierungsfreies und strombegrenzungsloses Schalten sowie eine lange Lebensdauer. Die entwickelten memristiven Bauelemente werden in Systeme, wie Kreuzpunkt-Strukturen und Ein-Transistor-ein-Memristor-Konfigurationen integriert. Hier wird die Eignung für effizientes neuromorphes Computing bewertet. Außerdem werden Methoden zur stufenlosen analogen Einstellung des Widerstands der Bauelemente demonstriert. Diese Eigenschaft ermöglicht effiziente neuromorphe Rechenschemata. Diese umfassende Studie beleuchtet die Beziehung zwischen den Bauelementparametern und den elektrischen Eigenschaften von mehrschichtigen memristiven Bauelementen auf Metalloxidbasis. Auf dieser Grundlage werden maßgeschneiderte Methoden für spezifische neuromorphe Anwendungen entwickelt.Multilayer metal-oxide-based-memristive devices are one of the most promising candidates for neuromorphic computing. However, specific applications of neuromorphic computing call for different requirements for memristive devices. Therefore, an open challenge in technological development is the tailored design of memristive devices for specific applications. In particular, multilayer stacks complicate fabrication processes due to a large number of device parameters such as staking sequences and thicknesses, quality, and property of each layer. Therefore, systematic investigations of the individual device parameters are particularly decisive. Moreover, they need to be combined with a profound understanding of the underlying physical processes to bridge the gap between material design and electrical characteristics of the resulting memristive devices. To obtain memristive devices with different resistance switching characteristics, various sequences and combinations of three metal oxide layers (TiOx, HfOx, and AlOx) are fabricated and studied. First, single-layer oxide devices are investigated to find desirable multilayer stacks for memristive devices. Second, TiOx/HfOx-based bilayer oxide devices are fabricated. Via systematic experiments and statistical analysis, it is shown that the stoichiometry, thickness, and device area influence operating voltages, non-linearity in resistive switching, and variability. Third, TiOx/AlOx/HfOx-based devices are fabricated. By adding AlOx into the bilayer oxide stacks, these trilayer devices present favorable electrical features for use in neuromorphic hardware, such as electroforming-free and compliance-free switching as well as long retention. The developed memristive devices are integrated into systems such as crossbar structures and one-transistor-one-memristor configurations. Here, suitability for efficient neuromorphic computing is assessed. Also, methods to tune the device resistance gradually in an analog fashion are demonstrated. This feature allows for efficient neuromorphic computation. This comprehensive study highlights the relationship between device parameters and electrical properties of multilayer metal-oxide-based memristive devices. On this basis, tailoring methodologies are established for specific neuromorphic applications

Engineering method for tailoring electrical characteristics in TiN/TiOx/HfOx/Au Bi-layer oxide memristive devices

Memristive devices have led to an increased interest in neuromorphic systems. However, different device requirements are needed for the multitude of computation schemes used there. While linear and time-independent conductance modulation is required for machine learning, non-linear and time-dependent properties are necessary for neurobiologically realistic learning schemes. In this context, an adaptation of the resistance switching characteristic is necessary with regard to the desired application. Recently, bi-layer oxide memristive systems have proven to be a suitable device structure for this purpose, as they combine the possibility of a tailored memristive characteristic with low power consumption and uniformity of the device performance. However, this requires technological solutions that allow for precise adjustment of layer thicknesses, defect densities in the oxide layers, and suitable area sizes of the active part of the devices. For this purpose, we have investigated the bi-layer oxide system TiN/TiOx/HfOx/Au with respect to tailored I-V non-linearity, the number of resistance states, electroforming, and operating voltages. Therefore, a 4-inch full device wafer process was used. This process allows a systematic investigation, i.e., the variation of physical device parameters across the wafer as well as a statistical evaluation of the electrical properties with regard to the variability from device to device and from cycle to cycle. For the investigation, the thickness of the HfOx layer was varied between 2 and 8 nm, and the size of the active area of devices was changed between 100 and 2,500 µm2. Furthermore, the influence of the HfOx deposition condition was investigated, which influences the conduction mechanisms from a volume-based, filamentary to an interface-based resistive switching mechanism. Our experimental results are supported by numerical simulations that show the contribution of the HfOx film in the bi-layer memristive system and guide the development of a targeting device

Serum YKL-40 levels correlate with infarct volume, stroke severity, and functional outcome in acute ischemic stroke patients.

YKL-40 is associated with various neurological disorders. However, circulatory YKL-40 levels early after onset of acute ischemic stroke (AIS) have not been systematically assessed. We aimed to identify the temporal changes and clinical usefulness of measuring serum YKL-40 immediately following AIS.Serum YKL-40 and C-reactive protein (CRP) levels were monitored over time in AIS patients (n = 105) and compared with those of stroke-free controls (n = 34). Infarct volume and stroke severity (National Institutes of Health Stroke Scale; NIHSS) were measured within 48 hours of symptom onset, and functional outcome (modified Rankin Scale; mRS) was measured 3 months after AIS.Within 12 hours of symptom onset, levels of YKL-40 (251 vs. 41 ng/mL) and CRP (1.50 vs. 0.96 µg/mL) were elevated in AIS patients compared to controls. The power of YKL-40 for discriminating AIS patients from controls was superior to that of CRP (area under the curve 0.84 vs. 0.64) and YKL-40 (r = 0.26, P<0.001) but not CRP levels were correlated with mRS. On day 2 of admission (D2), YKL-40 levels correlated with infarct volume and NIHSS. High YKL-40 levels predicted poor functional outcome (odds ratio 5.73, P = 0.03). YKL-40 levels peaked on D2 and declined on D3, whereas CRP levels were highest on D3.Our results demonstrate serial changes in serum YKL-40 levels immediately following AIS and provide the first evidence that it is a valid indicator of AIS extent and an early predictor of functional outcome

Ciliogenesis is reciprocally regulated by PPARA and NR1H4/FXR through controlling autophagy in vitro and in vivo

<p>The primary cilia are evolutionarily conserved microtubule-based cellular organelles that perceive metabolic status and thus link the sensory system to cellular signaling pathways. Therefore, ciliogenesis is thought to be tightly linked to autophagy, which is also regulated by nutrient-sensing transcription factors, such as PPARA (peroxisome proliferator activated receptor alpha) and NR1H4/FXR (nuclear receptor subfamily 1, group H, member 4). However, the relationship between these factors and ciliogenesis has not been clearly demonstrated. Here, we present direct evidence for the involvement of macroautophagic/autophagic regulators in controlling ciliogenesis. We showed that activation of PPARA facilitated ciliogenesis independently of cellular nutritional states. Importantly, PPARA-induced ciliogenesis was mediated by controlling autophagy, since either pharmacological or genetic inactivation of autophagy significantly repressed ciliogenesis. Moreover, we showed that pharmacological activator of autophagy, rapamycin, recovered repressed ciliogenesis in <i>ppara⁻^/− </i> cells. Conversely, activation of NR1H4 repressed cilia formation, while knockdown of NR1H4 enhanced ciliogenesis by inducing autophagy. The reciprocal activities of PPARA and NR1H4 in regulating ciliogenesis were highlighted in a condition where de-repressed ciliogenesis by NR1H4 knockdown was further enhanced by PPARA activation. The in vivo roles of PPARA and NR1H4 in regulating ciliogenesis were examined in greater detail in <i>ppara⁻^/⁻ </i> mice. In response to starvation, ciliogenesis was facilitated in wild-type mice via enhanced autophagy in kidney, while <i>ppara⁻^/⁻ </i> mice displayed impaired autophagy and kidney damage resembling ciliopathy. Furthermore, an NR1H4 agonist exacerbated kidney damage associated with starvation in <i>ppara⁻^/⁻ </i> mice. These findings indicate a previously unknown role for PPARA and NR1H4 in regulating the autophagy-ciliogenesis axis in vivo.</p

Levels of serum YKL-40 (A) and CRP (B) in acute ischemic stroke patients and controls.

<p>Each box indicates the median. Horizontal lines indicate the interquartile ranges. (<b>C</b>) Diagnostic accuracies of serum YKL-40 and CRP for discriminating acute ischemic stroke patients (n = 100; for statistical assessment of the differences between D1 and D2, 5 of 105 patients were excluded because they [n = 5] dropped out of the D2 test) from controls (n = 34) using receiver operating characteristic (ROC) curves. Numbers in square brackets indicate diagnostic accuracies (area under the ROC curves). D1, within 12 hours of symptom onset; D2, 18–24 hours from baseline (D1); CRP, C-reactive protein. *<i>P</i><0.05. ^a<i>P</i><0.05, vs. YKL-40 on D2. ^b<i>P</i><0.05, vs. CRP on D1. ^c<i>P</i><0.05, vs. CRP on D2. ^d<i>P</i><0.05, vs. YKL-40 on D1.</p

Multivariate-Adjusted odds ratios for Poor Functional Outcome Depend on D2 Serum YKL-40.

<p>D2, 18–24 hours from baseline; OR, odds ratio; CI, confidence interval.</p>a<p>Reference OR (1.00) is the lowest tertile of YKL-40 for poor outcome (mRS 4–6).</p>b<p>Adjusted factors: A = age and sex; B = A + hypertension, diabetes mellitus, hypercholesterolemia, and smoking; C = B+ previous stroke and D2 C-reactive protein level.</p>c<p><i>P</i><0.05.</p

Levels of serum YKL-40 (A) and CRP (B) depend on stroke subtype (in noncardiogenic stroke).

<p>Each box indicates the median. Horizontal lines indicate the interquartile ranges. D1, within 12 hours of symptom onset; D2, 18–24 hours from baseline (D1); CRP, C-reactive protein; SVO, small-vessel occlusion or lacunar; LAA, large artery atherosclerosis or atherothrombosis. *<i>P</i><0.05.</p

Correlation of YKL-40 and CRP Levels with Stroke Severity, Infarct volume, and Functional Outcome.

<p>D1, within 12 hours of symptom onset; D2, 18–24 hours from baseline (D1); CRP, C-reactive protein; NIHSS, National.</p><p>Institutes of Health Stroke Scale; mRS, modified Rankin Scale.</p>*<p><i>P</i><0.05.</p

Demographic Characteristics of AIS Patients and Controls.

<p>AIS, acute ischemic stroke; TOAST, Trial of Org 10172 in Acute Stroke Treatment criteria; SVO, small-vessel occlusion or lacunar; LAA, large artery atherosclerosis or atherothrombosis; CE, cardioembolic; NIHSS, National Institutes of Health Stroke Scale; IQR, interquartile range; NT, not tested; mRS, modified Rankin Scale.</p>*<p><i>P</i><0.05.</p