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Suppose we are given a discrete-valued time series $$X $$ X of observed events and an equally long binary sequence $$Y $$ Y that indicates whether something of interest happened at that particular point in time. We consider the problem of mining serial episodes, sequential patterns allowing for gaps, from $$X $$ X that reliably predict those interesting events. With reliable we mean patterns that not only predict that an interesting event is likely to follow, but in particular that we can also accurately tell how how long until that event will happen. In other words, we are specifically interested in patterns with a highly skewed distribution of delays between pattern occurrences and predicted events. As it is unlikely that a single pattern can explain a complex real-world progress, we are after the smallest, least redundant set of such patterns that together explain the interesting events well. We formally define this problem in terms of the Minimum Description Length principle, by which we identify the best patterns as those that describe the occurrences of interesting events $$Y $$ Y most succinctly given the data over $$X $$ X . As neither discovering the optimal explanation of $$Y $$ Y given a set of patterns, nor the discovery of optimal pattern set are problems that allow for straightforward optimization, we break the problem in two and propose effective heuristics for both. Through extensive empirical evaluation, we show that both our main method, Omen, and its fast approximation fOmen, work well in practice and both quantitatively and qualitatively beat the state of the art.

Additional file 1: Fig. S1. Distribution functions for different values of win the NLS model for t1 =1 µs. In the KAI model, a single characteristic time is assumed through a Dirac function. For small values of w, the functions assimilate.

During the last decade, valence change memory (VCM) has been extensively studied due to its promising features, such as a high endurance and fast switching times. The information is stored in a high resistive state (logcial '0', HRS) and a low resistive state (logcial '1', LRS). It can also be operated in two different writing schemes, namely a unipolar switching mode (LRS and HRS are written at the same voltage polarity) and a bipolar switching mode (LRS and HRS are written at opposite voltage polarities). VCM, however, still suffers from a large variability during writing operations and also faults occur, which are not yet fully understood and, therefore, require a better understanding of the underlying fault mechanisms. In this study, a new intrinsic failure mechanism is identified, which prohibits RESET times (transition from LRS to HRS) faster than 400 ps and possibly also limits the endurance. We demonstrate this RESET speed limitation by measuring the RESET kinetics of two valence change memory devices (namely Pt/TaO$_\mathrm{x}$/Ta and Pt/ZrO$_\mathrm{x}$/Ta) in the time regime from 50 ns to 50 ps, corresponding to the fastest writing time reported for VCM. Faster RESET times were achieved by increasing the applied pulse voltage. Above a voltage threshold it was, however, no longer possible to reset both types of devices. Instead a unipolar SET (transition from HRS to LRS) event occurred, preventing faster RESET times. The occurrence of the unipolar SET is attributed to an oxygen exchange at the interface to the Pt~electrode, which can be suppressed by introducing an oxygen blocking layer at this interface, which also allowed for 50 ps fast RESET times., 27 pages, 18 figures and 69 references

Epitaxial layers of ferroelectric orthorhombic HfO2 are frequently investigated as model systems for industrially more relevant polycrystalline films. The recent success in stabilizing the orthorhombic phase in the solid-solution cerium oxide – hafnium oxide system allows detailed investigations of external influences during fabrication. This report analyzes the ferroelectric properties of two thin film capacitors, which were post-deposition annealed in N2 and O2 atmospheres to achieve the orthorhombic phase after room temperature deposition. The samples, which exhibit very similar constituent phase, appear identical in conventional polarization-field hysteresis measurements. However, a significant switching speed difference is observed in pristine devices. Continued field cycling reduces the difference. Deeper analysis of switching transients based on the Nucleation Limited Switching model suggests that the O2 heat treatment atmosphere results in an altered oxygen vacancy profile, which is reverted during ferroelectric cycling.

Background In the ongoing COVID-19 pandemic, advanced age is a risk factor for a severe clinical course of SARS-CoV-2 infection. Thus, older people may benefit in particular from booster doses with potent vaccines and research should focus on optimal vaccination schedules. In addition to each individual’s medical history, immunosenescence warrants further research in this population. This study investigates vaccine-induced immune response over 1 year. Methods/design EU-COVAT-1-AGED is a randomised controlled, adaptive, multicentre phase II protocol evaluating different booster strategies in individuals aged ≥75 years (n=600) already vaccinated against SARS-CoV-2. The initial protocol foresaw a 3rd vaccination (1st booster) as study intervention. The present modified Part B of this trial foresees testing of mRNA-1273 (Spikevax®) vs. BNT162b2 (Comirnaty®) as 4th vaccination dose (2nd booster) for comparative assessment of their immunogenicity and safety against SARS-CoV-2 wild-type and variants. The primary endpoint of the trial is to assess the rate of 2-fold antibody titre increase 14 days after vaccination measured by quantitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA) against wild-type virus. Secondary endpoints include the changes in neutralising antibody titres (Virus Neutralisation Assay) against wild-type as well as against Variants of Concern (VOC) at 14 days and up to 12 months. T cell response measured by qPCR will be performed in subgroups at 14 days as exploratory endpoint. Biobanking samples are being collected for neutralising antibody titres against potential future VOC. Furthermore, potential correlates between humoral immune response, T cell response and neutralising capacity will be assessed. The primary endpoint analysis will be triggered as soon as for all patients the primary endpoint (14 days after the 4th vaccination dose) has been observed. Discussion The EU-COVAT-1-AGED trial Part B compares immunogenicity and safety of mRNA-1273 (Spikevax®) and BNT162b2 (Comirnaty®) as 4th SARS-CoV-2 vaccine dose in adults ≥75 years of age. The findings of this trial have the potential to optimise the COVID-19 vaccination strategy for this at-risk population. Trial registration ClinicalTrials.govNCT05160766. Registered on 16 December 2021. Protocol version: V06_0: 27 July 2022

Epitaxial layers of ferroelectric orthorhombic HfO

Background: In the ongoing COVID-19 pandemic, advanced age is a risk factor for a severe clinical course of SARS-CoV-2 infection. Thus, older people may benefit in particular from booster doses with potent vaccines and research should focus on optimal vaccination schedules. In addition to each individual’s medical history, immunosenescence warrants further research in this population. This study investigates vaccine-induced immune response over one year.Methods/Design: EU-COVAT-1-AGED is a randomised controlled, adaptive, multicentre phase II protocol evaluating different booster strategies in individuals aged ≥75 years (n=600) already vaccinated against SARS-CoV-2. The initial protocol foresaw a 3rd vaccination (1st booster) as study intervention. The present modified Part B of this trial foresees testing of mRNA-1273 (Spikevax®) vs. BNT162b2 (Comirnaty®) as 4th vaccination dose (2nd booster) for comparative assessment of their immunogenicity and safety against SARS-CoV-2 wild-type and variants. The primary endpoint of the trial is to assess the rate of 2-fold antibody titre increase 14 days after vaccination measured by quantitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA) against wild-type virus. Secondary endpoints include the changes in neutralising antibody titres (Virus Neutralisation Assay) against wild-type as well as against Variants of Concern (VOC) at 14 days and up to 12 months. T-cell response measured by qPCR will be performed in subgroups at 14 days as exploratory endpoint. Biobanking samples are being collected for neutralising antibody titres against potential future VOC. Furthermore, potential correlates between humoral immune response, T-cell response and neutralising capacity will be assessed.The primary endpoint analysis will be triggered as soon as for all patients the primary endpoint (14 days after the 4th vaccination dose) has been observed.Discussion: The EU-COVAT-1-AGED trial Part B compares immunogenicity and safety of mRNA-1273 (Spikevax®) and BNT162b2 (Comirnaty®) as 4th SARS-CoV-2 vaccine dose in adults ≥75 years of age. The findings of this trial have the potential to optimise the COVID-19 vaccination strategy for this at-risk population.

Additional file 1. EU-COVAT-1-AGED Intervention in Part A – 3rd vaccination

Threshold switching (TS) devices are of great interest for low power artificial neuron applications. In this work, we present an Ag/HfO 2 /Pt based TS device with an ultra-low leakage current ( 1011), fast turn-on and turn-off speeds (< 300 ns and < 250 ns, respectively), low threshold voltage (< 0.2 V), and a stable TS performance. Furthermore, we demonstrate the integrate-and-fire (I&F) neuron functionality of our device experimentally. The inherent stochastic behavior and simple structure make TS devices an ideal candidate for replacing the complex and large-size CMOS (complementary metal-oxide-semiconductor) based neurons. This paves the way towards building energy- and area-efficient neuromorphic systems.

With the arrival of the Internet of Things (IoT) and the challenges arising from Big Data, neuromorphic chip concepts are seen as key solutions for coping with the massive amount of unstructured data streams by moving the computation closer to the sensors, the so-called “edge computing.” Augmenting these chips with emerging memory technologies enables these edge devices with non-volatile and adaptive properties which are desirable for low power and online learning operations. However, an energy- and area-efficient realization of these systems requires disruptive hardware changes. Memristor-based solutions for these concepts are in the focus of research and industry due to their low-power and high-density online learning potential. Specifically, the filamentary-type valence change mechanism (VCM memories) have shown to be a promising candidate In consequence, physical models capturing a broad spectrum of experimentally observed features such as the pronounced cycle-to-cycle (c2c) and device-to-device (d2d) variability are required for accurate evaluation of the proposed concepts. In this study, we present an in-depth experimental analysis of d2d and c2c variability of filamentary-type bipolar switching HfO2/TiOx nano-sized crossbar devices and match the experimentally observed variabilities to our physically motivated JART VCM compact model. Based on this approach, we evaluate the concept of parallel operation of devices as a synapse both experimentally and theoretically. These parallel synapses form a synaptic array which is at the core of neuromorphic chips. We exploit the c2c variability of these devices for stochastic online learning which has shown to increase the effective bit precision of the devices. Finally, we demonstrate that stochastic switching features for a pattern classification task that can be employed in an online learning neural network.

Kurzfassung Zentrale Hemmnisse für die Flexibilisierung, Wandlungs- und Integrationsfähigkeit von Karosseriebauanlagen sind die Aufbaulinien und die Bauteillogistik. Inzwischen ist es uns gelungen, das Szenario eines zukünftigen Karosseriebaus, der allen absehbaren Anforderungen gerecht wird, in einem Layout zu beschreiben. Dafür wurden die heutigen Restriktionen und Hemmnisse analysiert, Alternativlösungen ermittelt und zu einem schlüssigen Gesamtbild entwickelt: der „Boxenstoppfertigung“. Diese ermöglicht die Unabhängigkeit der Karosseriefertigung von spezifischen Produktanforderungen und gewährleistet maximale Flexibilität.

Redox-type resistive random access memories based on transition-metal oxides are studied as adjustable two-terminal devices for integrated network applications beyond von Neumann computing. The pre...

Bipolar redox-based resistive random-access memory cells are intensively studied for new storage class memory and beyond von Neumann computing applications. However, the considerable variability of the resistance values in ON and OFF state as well as of the SET voltage remains challenging. In this paper, we discuss the physical origin of the significant reduction in the switching variability of HfO2-based devices achieved by the insertion of a thin TiO x layer between the HfO2 layer and the oxygen exchange metal layer. Typically, HfO2 single layer cells exhibit an abrupt SET process, which is difficult to control. In contrast, self-compliance effects in the HfO2/TiO x bilayer devices lead to an increased stability of SET voltages and OFF-state resistances. The SET process is gradual and the RESET becomes abrupt for higher switching currents. Comparison of the experimental data with simulation results achieved from a physics-based compact model for the full description of the switching behavior of the single layer and bilayer devices clearly reveal three major effects. The TiO x layer affects the temperature distribution during switching (by modifying the heat dissipation), forms an additional series resistance and changes the current conduction mechanism in the OFF state of the bilayer device compared to the single layer device.

Umfrageergebnisse zeigen, dass der Larm in seinen vielfaltigen Formen zu den starksten Beeintrachtigungen im Wohnumfeld gehort. Nach Schatzungen der Weltgesundheitsorganisation (WHO) gehen in Europa jahrlich ca. eine Million beschwerdefreie Jahre durch die Wirkungen des Umgebungslarms verloren. Der vorliegende Beitrag diskutiert die Larmwirkungsaspekte am Beispiel des Verkehrslarms, auf den sich die meisten Larmwirkungsstudien zum Umgebungslarm beziehen. Immer mehr Studien weisen Assoziationen zwischen Verkehrslarm und vaskularen und metabolischen Erkrankungen sowie auch psychischen Erkrankungen auf. Noch ist zu wenig uber die kausalen Mechanismen bekannt, auch wenn es hierzu eine Reihe von Modellvorstellungen gibt. Fest steht jedoch: Es ist heutzutage nicht die Frage, ob Larm auch auf extraauraler Ebene krank machen kann, sondern unter welchen Bedingungen und in welchem Risikoausmas. Das hohe Ausmas der Beeintrachtigungen durch Larm verweist auf Handlungsbedarf in der Larmschutzpolitik. Zum Schutz vor Verkehrslarm haben Bund, Lander und Kommunen in den letzten Jahren – z. B. im Rahmen der Larmaktionsplanung – zahlreiche Initiativen ergriffen. Besonders bemerkenswert sind die innovativen Masnahmen, Instrumente und Programme gegen den Schienenverkehrslarm. Bei der wichtigsten Verkehrslarmquelle, dem Strasenverkehr, ist weniger Fortschritt erzielt worden. Auch beim Fluglarm steht die Uberprufung und Weiterentwicklung wichtiger Gesetze noch aus. Zugunsten innerstadtischer Verdichtung wurde das Larmschutzniveau bei Sport- und Gewerbelarm abgesenkt. Signifikante gesundheitsrelevante Absenkungen der Larmbelastungen sind – auser im Bereich des Schienenverkehrs – daher in naher Zukunft nicht zu erwarten.

Redox-type resistive random access memories based on transition-metal oxides are studied as adjustable two-terminal devices for integrated network applications beyond von Neumann computing. The prevailing, so-called, counter-eight-wise (c8w) polarity of the switching hysteresis in filamentary-type valence change mechanism devices originates from a temperature- and field-controlled drift-diffusion process of mobile ions, predominantly oxygen vacancies in the switching oxide. Recently, a bipolar resistive switching (BRS) process with opposite polarity, so-called, eight-wise (8w) switching, has been reported that, especially for TiO

Redox-based resistive random access memories (ReRAM) are promising candidates for the use in ‘beyond-von Neumann’ architectures. One key issue for utilizing ReRAM for e.g. neuromorphic applications is a gradual SET and RESET behavior, allowing to write various resistance states emulating synaptic weights. However, a typical SET event for filamentary-like valence change mechanism devices is happening abrupt due to its physical principle. In this work we demonstrate a gradual SET behavior for $\text{HfO}_{2}/\text{TiO}_{\mathrm{x}}$ ReRAM cells in pulse mode. The results are discussed in view of the inherent properties of the particular bilayer structure.

In this article, the effects of oil price changes on the stock return of 17 German DAX companies are studied from February 1982 to July 2007. By applying panel estimations, we initially identify a nonlinear and asymmetric relationship between oil prices (quoted in US dollar) and the German stock market,which is consistent with a signalling (transmission) channel. Additionally, further evidence is provided for the signalling channel on a disaggregated and daily data base. The results reveal, however, that only certain specific industries are affected by oil price shocks, whereas others remain unaffected. These varying effects of oil price shocks mainly result from the cost- and demand-side dependence on oil that different companies are exposed to.

On the one hand, any licensed physician is allowed to attest a prospective diver’s fitness to dive, even without a relevant further qualification. On the other hand, s/he should certainly not do so after merely reading this short CME article. Not for nothing does the fitness to dive manual comprise more than 200 printed pages, which a doctor should know before attesting anything. There is no such thing as “unfitness to dive.” Aviation physicians have the right to bar a would-be pilot from flying a plane; the reason is that such an undertaking may put others at risk in case of a crash. Diving medicine specialists cannot bar persons from diving because recreational diving puts only the divers themselves at risk. Diving is always the diver’s own responsibility. A medical certificate attesting fitness to dive mainly serves to protect diving schools and tour operators. Making such a certificate a requirement will have a single positive effect in that recreational divers are obliged to submit to a diving medical consultation, in which they will receive extensive and individual information on what their personal risk factors are. Such advice is the main task of a diving medicine specialist; the paper certificate is an optional extra. What the CME article is unforgivably lacking is any mention of psychological contraindications. Most life-threatening diving incidents are caused by psychological slips. Diving medicine specialists should elicit information on how someone deals with stress, how willing they are to experience fear, and how they handle high-risk behavior. A diagnosis of a “phobic patient” is a relative contraindication, as is that of a “carefree/careless person.” Hyperventilation in a scuba diver having a panic attack under water is not a good scenario. Personality disorders require critical evaluation. Further contraindications include depression, suicidality, manic hubris, psychotic symptoms with misjudgment of reality, and addictive behaviors including and excluding substances. It goes without saying that recreational divers should be sober and not currently be taking psychotropic drugs. In my view, the psychological situation of recreational divers is more important than their lung function or cardiac output when the objective is to prevent diving accidents by means of giving high-quality advice.

With the Green Paper on Future Noise Policy published in November 1996, the European Commission began to step up its activities in the field of European noise abatement policy including the railway sector. The Commission has convened various working groups (WG) on noise reception and emissions in order to develop proposals for the new European noise policy. The Railway Noise WG started its work in December 1999. Furthermore, the Commission is going to enforce noise emission limits for high-speed and conventional train sets operating on the trans-European network within the Interoperability Directives of the European Union. This paper reports on the reasons for the new European noise policy. It describes how railway noise regulations are developed within the framework of the Interoperability Directives. First, limit proposals for high-speed train sets are presented. Results of the activities of the Railway Noise WG are described.

In a previous paper we demonstrated that Hammondia heydorni-like oocysts isolated in 1996 from a naturally infected dog could not be distinguished from the isolate Neospora caninum NC-1. The isolate, designated as H. heydorni-Berlin-1996, was cyclically transmitted using dogs as the final hosts. The present study provides information on the antibody responses of the dogs used for the cyclical transmission of this isolate. The majority of dogs that had shed oocysts showed no sero-conversion with respect to N. caninum tachyzoite surface or immunodominant antigens, either in the indirect fluorescent antibody test or in two Western-blot-based tests. In addition to the examination of responses to immunodominant antigens, we also analysed the antibody reactions of dogs to a high-molecular-weight antigen (152 kDa) in the tachyzoite antigen preparation. The antibodies against this antigen appeared after the dogs had been fed infected intermediate host tissues and shed oocysts. The reaction was observed in dogs between day 35 and day 447 after feeding of intermediate host tissues. Therefore, our study provides initial information on a 152 kDa tachyzoite antigen, which might be a suitable candidate to identify dogs with a history of shedding N. caninum oocysts.

This 1-year, double-blind, active-controlled, multicenter study compared the efficacy and safety of atorvastatin to pravastatin and evaluated their ability to achieve target low-density lipoprotein cholesterol (LDL-C) levels in patients with hypercholesterolemia. Patients were stratified to risk factor groups based upon European Atherosclerosis Society (EAS) guidelines before randomization to atorvastatin 10 or 20 mg or pravastatin 20 or 40 mg once daily. Target LDL-C levels for patients with mild/moderate risk and severe risk were

Nuclear energy cannot be avoided in the near future. To regain public acceptance the safety of nuclear power plants has to be increased. Consequently, feasibility studies have been carried out for a containment proposal for future pressurized water reactors which will keep people unharmed even in the case of severe nuclear accidents under the assumption “all that can go wrong, will go wrong”. The main features of the design concept are a core melt cooling and retention device, a passively acting cooling system to remove the decay heat and a double-wall containment which is able to withstand high static and dynamic internal pressures due to hydrogen detonation. Internal structures are designed to resist extreme loadings resulting from various accident scenarios including in-vessel steam explosion and vessel failure under high system pressure.

The Handbook of Iconometry (ca. 1687) reproduces, in facsimile, a lavishly illustrated treatise describing the iconometic principles and measurements at the heart of the 17th-century art of Tibet. It includes over 150 drawings of buddhas, bodhisattvas and divinities, 70 script types and 14 stupa models from the rich world of Indo-Tibetan Buddhism.

Noise belongs to the severest environmental impairments in towns, with road traffic being the most annoying noise source. The reduction of these impairments and the precaution against new noise impacts is an important task of the communities. However, many of the potential abatement measures are not in the responsibility of the communities. In most European countries, noise emission regulations for road and rail vehicles and outdoor machinery are nowadays enforced by the European Union. Noise reception limits are generally enforced by national laws. Therefore, efficient noise abatement in towns has to be coordinated with the regional, national and supranational, i.e. European noise policy. The most important fields of action for the urban noise abatement are the roads, railways and airports with heavy traffic. For the avoidance of health risks due to noise here short-term reductions are needed, which can generally be achieved only by a combination of measures for which different stakeholders are responsible. This underlines the importance of integrated and coordinated noise abatement concepts.

The Handbook of Iconometry (ca. 1687) reproduces, in facsimile, a lavishly illustrated treatise describing the iconometic principles and measurements at the heart of the 17th-century art of Tibet. It includes over 150 drawings of buddhas, bodhisattvas and divinities, 70 script types and 14 stupa models from the rich world of Indo-Tibetan Buddhism.

The Handbook of Iconometry (ca. 1687) reproduces, in facsimile, a lavishly illustrated treatise describing the iconometic principles and measurements at the heart of the 17th-century art of Tibet. It includes over 150 drawings of buddhas, bodhisattvas and divinities, 70 script types and 14 stupa models from the rich world of Indo-Tibetan Buddhism.

The Handbook of Iconometry (ca. 1687) reproduces, in facsimile, a lavishly illustrated treatise describing the iconometic principles and measurements at the heart of the 17th-century art of Tibet. It includes over 150 drawings of buddhas, bodhisattvas and divinities, 70 script types and 14 stupa models from the rich world of Indo-Tibetan Buddhism.

The Handbook of Iconometry (ca. 1687) reproduces, in facsimile, a lavishly illustrated treatise describing the iconometic principles and measurements at the heart of the 17th-century art of Tibet. It includes over 150 drawings of buddhas, bodhisattvas and divinities, 70 script types and 14 stupa models from the rich world of Indo-Tibetan Buddhism.

Duisburg, Essen, Univ., Diss., 2010