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Nord Stream 2 is one of the most discussed energy projects, which affects the economic and political interests of many countries, not only the direct participants. Despite some uncertainty, the project is highly likely to be completed. In this regard, it is important to understand what impact it will have on the European gas market. This article proposes a simulation model for calculating the total cost of construction of the Nord Stream 2 and determines the cost of natural gas. It was concluded that Nord Stream 2 has an economic advantage overliquified natural gas (LNG) delivery schemes, a strategic value for the economies of the EU countries and will ensure the stability of gas supply, which is undoubtedly a priority for European energy policy.

Undisturbed bioelectricity is a prerequisite for normal organ function. This is especially true for organs with high electrical activity such as the heart and the nervous system. Under clinical conditions, however, this can hardly be determined in patients with disturbed organ function and is therefore largely ignored. Here, based on clinical data, we will discuss whether the direct application of an external electric current (in the physiological μA range) together with an electrical field to hearts with impaired pump function can explain the functional improvement of the hearts by edema reduction triggered by electro-osmosis.

Eisenmangel ohne Anamie wird zunehmend als eine klinisch relevante, und zu erheblicher Morbiditat fuhrende Erkrankung anerkannt. Eisen spielt eine Rolle im Immunsystem und beeinflusst die Funktionalitat der Muskulatur sowie der Neuronen. Klinisch manifestiert sich der Eisenmangel ohne Anamie durch die Symptome einer Fatigue, ein geistiger und korperlicher krankhafter Erschopfungszustand welcher unverhaltnismasig von vorrausgegangenen korperlichen Belastungen auftritt und nicht durch Ruhe- bzw. Schlafphasen behoben werden kann. Diese durch Eisenmangel verursachte Fatigue kann allerdings mit einer parenteralen Eisenzufuhr erfolgreich behandelt werden. Dieser Ubersichtsartikel soll eine Zusammenfassung uber den aktuellen Stand der Wissenschaft, inklusive Entstehung, Diagnose und Behandlung von Eisenmangel ohne Anamie bieten.

Background Obese patients are at risk for rapid oxygen desaturation during anesthesia induction. Apneic oxygenation with regular flow oxygen insufflation has successfully been used to prolong the duration of safe apnea without desaturation (DAWD) in morbidly obese patients. Using high-flown nasal insufflation of oxygen (HFNI) for apneic oxygenation might further increase the DAWD. Objectives To compare the duration of safe apnea using high-flown nasal insufflation of oxygen or standard flow oxygen insufflation for apneic oxygenation in a simulated difficult intubation scenario in patients with morbid obesity. Setting Operating room, University Hospital, Austria. Methods In a prospective, randomized, clinical trial, patients received standardized preoxygenation and anesthesia induction. Apneic oxygenation was performed using standard nasal prongs (10 L/min) or HFNI (120 L/min) during laryngoscopy. A Cormack-Lehane 3° view was maintained until the oxygen saturation on pulse oximetry (Sp O 2) dropped ≤95% or for a maximum of 15 minutes. The primary outcome of this study was to compare the duration of safe apnea using HFNI or standard flow oxygen insufflation for apneic oxygenation. In addition, arterial blood gas results, and airway pressures were investigated. Results In 40 patients with morbid obesity (body mass index [BMI] >40 kg/m2) and the American Society of Anesthesiologists physical classification ≤3 who underwent bariatric surgery, the median duration of safe apnea was 601 (268–900) seconds in the standard group and 537 (399–808) seconds in the HFNI group (P = .698). No differences in arterial blood gas results were observed between the groups. The median airway pressure was 0 (0–0) cm H2O in the standard group and 1 (0–2) cm H2O in the HFNI group (P = .005). Conclusion Compared with standard nasal apneic oxygenation, HFNI did not increase the duration of safe apnea in patients with morbid obesity. A significant but clinically negligible higher airway pressure was observed when using HFNI.

Spin-momentum locking is a peculiar effect in the near-field of guided optical or plasmonic modes. It can be utilized to map the spinning or handedness of electromagnetic fields onto the propagation direction. This motivates a method to probe the circular dichroism of an illuminated chiral object. In this work, we demonstrate local, subdiffraction limited chiral coupling of light and propagating surface plasmon polaritons in a self-assembled system of a gold nanoantenna and a silver nanowire. A thin silica shell around the nanowire provides precise distance control and also serves as a host for fluorescent molecules, which indicate the direction of plasmon propagation. We characterize our nanoantenna-nanowire systems comprehensively through correlated electron microscopy, energy-dispersive X-ray spectroscopy, dark-field, and fluorescence imaging. Three-dimensional numerical simulations support the experimental findings. Besides our measurement of far-field polarization, we estimate sensing capabilities and derive not only a sensitivity of 1 mdeg for the ellipticity of the light field, but also find 103 deg cm2/dmol for the circular dichroism of an analyte locally introduced in the hot spot of the antenna-wire system. Thorough modeling of a prototypical design predicts on-chip sensing of chiral analytes. This introduces our system as an ultracompact sensor for chiral response far below the diffraction limit.

This letter investigates the impact of read operation on the electrical properties of hafnium oxide-based ferroelectric field-effect transistors (FeFETs). We report that a quasi-static read may induce a series of phenomena, including a severe underestimation of the memory window, undesirable loss of the stored state, i.e. destructive read, increased variability and an apparent steep-slope behavior with a subthreshold slope lower than 7 mV/decade, which are not present under a fast read. We explain the results with the time-voltage dependence for the ferroelectric switching. Based on this, we provide comprehensive yet essential guidelines for disturb-free write and read operations.

Background Cannabis has increasingly been used for medical and recreational purposes. The main pharmacological compound in cannabis is tetrahydrocannabinol (THC), which has sedative, anxiolytic and analgesic effects. In some animal models, THC has also been shown to reduce the minimum alveolar concentration (MAC) of halothane and cyclopropane, but its effect on sevoflurane, currently the most commonly used inhalational anaesthetic agent, has not been investigated. Objective To investigate the effect of THC on the MAC of sevoflurane in rats. Methods Observer-blinded, randomised controlled trial. Setting Centre for Biomedical Research of the Medical University of Vienna, 2019. Individuals Thirty-eight adult Wistar rats. Interventions The rats were allocated randomly into one of two groups. Group A received THC 10 mg kg and group B received the corresponding volume of placebo via gastric gavage (administration through a tube placed in the distal oesophagus). The rats were then individually anaesthetised in an airtight sevoflurane-flooded chamber, and the MAC in both groups was determined using Dixon's up-and-down method. Blood samples were drawn to measure serum concentrations of THC. Main outcome measures The primary outcome was the MAC of sevoflurane in Groups A and B. Results The bootstrap estimate of the MAC of sevoflurane was 2.1 (95% confidence interval 1.8 to 2.4) vol% in the THC group and 2.8 (95% confidence interval 2.7 to 2.9) vol% in the placebo group, corresponding to a significant MAC reduction of 26% in response to THC. Conclusion Gastric administration of THC 10 mg kg significantly reduced the MAC of sevoflurane by 26%. Trial registration Not applicable.

Long data retention is a critical requirement for many of the potential applications of HfO2-based ferroelectric field-effect transistors (FeFETs). However, methods for its rapid assessment are still missing. In this article, we report a detailed investigation of the retention and switching properties of FeFETs fabricated in the 28-nm high- ${k}$ metal gate technology. We identify a clear correlation between the two properties and propose a method for fast prediction of the device retention behavior, which can be easily adopted to judge different fabrication processes. Finally, we extend the validity of the method to a direct assessment of disturb-free operating conditions, which may be particularly valuable for FeFET array operation.

Background and Objective BC 007 is a substance with a novel and innovative mode of action for the first-time causal treatment of chronic heart failure, associated with the occurrence of autoantibodies against the β1-adrenoceptor, and other diseases of mostly the heart and vascular system, being accompanied by the occurrence of functionally active agonistic autoantibodies against G-protein-coupled receptors (fGPCR-AAb). The proposed mechanism of action of BC 007 is the neutralisation of these pathogenic autoantibodies which stimulate the respective receptor. To evaluate the safety, tolerability, pharmacokinetics and mode of action of BC 007, single intravenous infusions of increasing concentration were given to healthy young males and healthy elderly autoantibody-negative and autoantibody-positive participants of both sexes. Methods This study was subdivided into three parts. Part A was a single-centre, randomised, double-blind, placebo-controlled safety and tolerability study including healthy young male autoantibody-negative Whites (N = 23) and Asians (N = 1), testing doses of 15, 50 and 150 mg BC 007 (Cohorts 1–3) and elderly male and female Whites (N = 8), testing a dose of 150 mg BC 007 (Cohort 4), randomly assigned in a 3:1 ratio to BC 007 or placebo. Open-label Part B included fGPCR-AAb-positive subjects (50 and 150 mg BC 007, Cohorts 1 and 2, respectively). Open-label Part C included fGPCR-AAb-positive subjects for testing doses of 300, 450, 750, 1350 mg and 1900 mg BC 007. Lower doses were either given as an infusion or divided into a bolus plus infusion up to a dose of 300 mg followed by a constant bolus of 150 mg up to a dose of 750 mg, while at doses of 1350 mg and 1900 mg it was a slow infusion with a constant infusion rate. Infusion times increased with increasing dose from 20 min (15, 50 or 150 mg) to 40 min (300, 450 or 750 mg), 75 min (1350 mg) and 105 min (1900 mg). Results The mean observed BC 007 area under the concentration–time curve (AUC0–24) increased with increasing dose in a dose proportional manner (slope estimate of 1.039). No serious adverse events were observed. Drug-related adverse events were predominantly the expected mild-to-moderate increase in bleeding time (aPTT), beginning with a dose of 50 mg, which paralleled the infusion and returned to normal shortly after infusion. fGPCR-AAb neutralisation efficiency increased with increasing dose and was achieved for all subjects in the last cohort. Conclusion BC 007 is demonstrated to be safe and well tolerated. BC 007 neutralised fGPCR-AAb, showing a trend for a dose-response relationship in elderly healthy but fGPCR-AAb-positive subjects. ClinicalTrials.gov Registration Number NCT02955420.

Aims Aptamer BC 007, a 15‐mer single‐strand DNA oligonucleotide (5'‐GGTTGGTGTGGTTGG‐3'), was developed to neutralize functional autoantibodies that bind to the extracellular domains of G protein‐coupled receptors (GPCR‐AAB), leading to the modulation of receptor‐mediated signalling cascades that induce pathophysiological states. Among the GPCR‐AAB, there are those directed against the β1‐adrenergic receptor (β1‐AAB) that are highly present in patients with dilated cardiomyopathy (DCM) and are increasingly accepted as disease drivers. Using Doberman Pinschers (DP) with DCM, which possess similarities with human DCM among these β1‐AAB positivity for that the disease‐driving role in DP DCM was demonstrated, the safety of BC 007, efficacy for neutralizing β1‐AAB, and the DP's outcome were investigated. Methods and results Fourteen client‐owned β1‐AAB‐positive DP with electrocardiographically and echocardiographically indicated DCM were treated with BC 007. For controlling, two groups were created: 14 β1‐AAB‐positive DP with DCM not treated with BC 007 (Control 1) and 14 DP with DCM closely matched to the BC 007‐treated DP (Control 2), retrospectively selected from the institutional database of DP. After treatment, DP were monitored both echocardiographically, and for β1‐AAB, and survival curves were calculated. Based on clinical and laboratory examination, no adverse effects associated with BC 007 treatment were observed during the study. Forty‐eight hours after treatment, the DP's blood was free of β1‐AAB, which led to a reduction or stabilization of left ventricular end‐systolic volume (ESVI) during β1‐AAB free time in 10 of the treated DP. In one DP, where β1‐AAB returned after 3 months and ESVI worsened again, a second BC 007 treatment after 9 months again cleared the blood from β1‐AAB and improved the ESVI. Compared with the controls, DP treated with BC 007 showed a significantly longer survival time [572 days, interquartile range (IQR) 442–840 days] vs. Control group 1 (266 days, IQR 97–438 days; logrank: P = 0.009) and Control group 2 (229 days, IQR 174–319 days; logrank: P = 0.012). Conclusions Treatment with BC 007 for β1‐AAB neutralization was safe, resulted in a long‐lasting reduction of β1‐AAB combined with improved cardiac function and prolonged the survival of DP with DCM. Using a natural large animal model of DCM considered superior to small animal models of immunization‐induced cardiomyopathy, combined with a study design comparable with clinical trials, we believe that our results provide the basis for optimism that treatment with BC 007 might also be effective in human patients with DCM.

Our research at the large LBK settlement site of Vráble, southwest Slovakia, revealed dynamics of social integration and antagonisms unfolding in an agglomerated, early farming community. During its lifespan from 5250 to 4950 bc, it constantly grew until around 5050 bc it was inhabited by about 70 contemporaneous longhouses. We found that Vráble consisted of markedly autonomous farmstead units that were held together by village-wide social institutions including sharing and communality. Nevertheless, from the beginning, a contradiction between particular farmstead and collective village and neighbourhood interests existed and rose. Towards the end of the village's existence, around 5075 bc an elaborate enclosure was constructed around one of the three neigbourhoods, actively blocking contact with the others. Along this enclosure, human bodies were deposited, showing a social categorization that we interpret as relating to social inequality. This rising level of conflict and emerging social inequality was, we argue, not sustainable under the conditions of early farming societies and led to the village's abandonment at 4950 bc.

Clinical features of Corona Virus Disease 2019 (COVID-19) are caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Acute infection management is a substantial health care issue, and the development of a Long-Covid syndrome (LCS) is extremely challenging for patients and physicians. It is associated with a variety of characteristics as e.g. impaired capillary microcirculation, chronic fatigue syndrome (CFS), pro-inflammatory cytokines, and functional autoantibodies targeting G-protein coupled receptors (GPCR-AAb). Here, we present a case report of a successful healing of LCS with BC 007 (Berlin Cures, Berlin, Germany), a DNA aptamer drug with high affinity to GPCR-AAbs that neutralizes these AAbs. A patient with a documented history of glaucoma, recovered from mild COVID-19, but still suffered from chronic fatigue syndrome, loss of taste and impaired capillary microcirculation in the macula and peripapillary region. He was positively tested for various targeting GPCR-AAbs. Within 48 h after a single BC 007 treatment, GPCR-AAbs were functionally inactivated and remained inactive during the observation period of 4 weeks. This observation was accompanied by a constant improvement of the patient’s fatigue symptoms, and taste as well as retinal capillary microcirculation. Therefore, it might be that removal of GPCR-AAb ameliorates characteristics of the Long-Covid-Syndrome such as capillary impairment, loss of taste and CFS.

The diverse experiences regarding the failure of tested drugs in the fight against COVID‐19 made it clear that one should at least question the requirement to apply classical preclinical development strategies that demand cell and animal efficacy models to be tested before going into clinical trials. Most animals are not susceptible to infection with SARS‐CoV‐2, and so this led to one‐sided virus replication experiments in cells and the use of animal models that have little in common with the complex pathogenesis of COVID‐19 in humans. Therefore, non‐clinical development strategies were designed to meet regulatory requirements, but they did not truly reflect the situation in the clinic. This has led the search for effective agents astray in many cases. As proof of this statement, we now bring together the results of such required preclinical experiments and compare with the results in clinical trials. Two clear conclusions that can be drawn from the experience to date: The required preclinical models are unsuitable for the development of innovative treatments medical devices in the case of COVID‐19 and mono‐action strategies (e.g. direct antivirals) are of very little or no benefit to patients under randomized,blinded conditions. Our hypothesis is that the complex situation of COVID‐19 may benefit from multi‐mode drugs. Here, the molecular class of aptamers could be a solution.

The ultimate goal in modern secure e-voting is to enable everyone to verify whether the final election result correctly reflects the votes chosen by the (human) voters, without exposing how each individual voted. These fundamental security properties are called end-to-end verifiability and voter privacy. Unfortunately, it turns out to be very challenging to pursue these properties simultaneously, especially when the latter must be future-proofed against the rise of quantum computers. In this work, we show, for the first time, a practical approach to do this. We present Epoque, the first end-to-end verifiable, voter-private, post-quantum-secure homomorphic e-voting protocol. It achieves its properties through the combination of practical lattice-based cryptographic primitives only, in a novel way. We formally prove all our security claims under common trust and hardness assumptions. At the core of Epoque lies an efficient identity-based encryption (IBE) scheme with blazingly fast master-key decryption. It is the component that makes the efficient tallying of thousands or millions of ballots a practical possibility. In order to demonstrate its practicality, we fully implemented it and provide detailed benchmarks; we believe this latter contribution is of independent interest beyond the specific e-voting application.

A multi-level cell (MLC) operation as a 1–3 bit/cell of the FeFET emerging memory is reported by utilizing optimized Si doped hafnium oxide (HSO) and hafnium zirconium oxide (HZO) based on ferroelectric laminates. An alumina interlayer was used to achieve the thickness independent of the HSO and HZO-based stack with optimal ferroelectric properties. Various split thicknesses of the HSO and HZO were explored with lamination to increase the FeFET maximum memory window (MW) for a practical MLC operation. A higher MW occurred as the ferroelectric stack thickness increased with lamination. The maximum MW (3.5 V) was obtained for the HZO-based laminate, the FeFETs demonstrated a switching speed (300 ns), 10 years MLC retention, and 104 MLC endurance. The transition from instant switching to increased MLC levels was realized by ferroelectric lamination. This indicated an increased film granularity and a reduced variability through the interruption of ferroelectric columnar grains. The 2–3 bit/cell MLC levels and maximum MW were studied in terms of the size-dependent variability to indicate the impact of the ferroelectric area scaling. The impact of an alumina interlayer on the ferroelectric phase is outlined for HSO in comparison to the HZO material. For the same ferroelectric stack thickness with lamination, a lower maximum MW, and a pronounced wakeup effect was observed in HSO laminate compared to the HZO laminate. Both wakeup effect and charge trapping were studied in the context of an MLC operation. The merits of ferroelectric stack lamination are considered for an optimal FeFET-based synaptic device operation. The impact of the pulsing scheme was studied to modulate the FeFET current to mimic the synaptic weight update in long-term synaptic potentiation/depression.

Current therapies significantly improve survival and clinical endpoints in patients suffering from chronic heart failure with reduced ejection fraction (HFrEF), but most are not sufficient to reverse adverse remodeling and improve myocardial contractility. Herein, we report the first-in-man experience with a novel fully implantable device for cardiac electrical microcurrent (C-MIC) application. A 79-year-old man suffering from HFrEF (dilated cardiomyopathy, NYHA class III, left ventricular ejection fraction 30%) successfully underwent implantation of the C-MIC device through left anterolateral thoracotomy. At 30-day follow-up, no device-related complications were observed, demonstrating feasibility of C-MIC implantation in a patient suffering from HFrEF.

Using psychology professors as participants, the present study investigates how publications in low-impact psychology journals affect evaluations of a hypothetical tenure-track psychology job applicant. Are "weak" publications treated as evidence for or against a candidate's ability? Two experiments revealed that an applicant was rated as stronger when several weak publications were added to several strong ones and was rated as weaker when the weak publications were removed. A third experiment showed that the additional weak publications were not merely viewed as a signal of additional strong publications in the future; instead, the weak publications themselves appear to be valued. In a fourth and final experiment, we found that adding a greater number of weak publications also strengthened the applicant, but not more so than adding just a few. The study further suggests that the weak publications may signal ability, as applicants with added weak publications were rated as both more hardworking and more likely to generate innovative research ideas. Advice for tenure-track psychology applicants: Do not hesitate to publish in even the weakest journals, as long as it does not keep you from publishing in strong journals. Implications of the market rewarding publications in low-impact journals are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Introduction A subpopulation of patients with hydrocephalus and idiopathic intracranial hypertension (IIH) treated for elevated intracranial pressure (ICP) with a cerebrospinal fluid (CSF) shunt may continue to suffer from symptoms or develop new symptoms despite valve adjustments. The use of telemetric ICP measurements may help confirm a clinical suspicion of CSF under- or overdrainage in these patients. However, point in time, duration and activity during the measurements, which may influence the results, have never been standardized. We devised a simple and repeatable maneuver for outpatient telemetric ICP recording. The aim of this study is to evaluate its test-retest reliability. Methods Data of patients who underwent ventriculoperitoneal or ventriculoatrial shunt placement and subsequent telemetric ICP sensor implantation were retrospectively reviewed. Telemetric ICP recordings in these patients were conducted in a standardized manner: The standing-supine-sitting-paradigm requires postural changes in 10-minute intervals over 30 minutes. First, the patient is requested to walk (upright body position), secondly to lay down (supine body position), and lastly to sit down with a headrest elevation of 60°. All ICP measurements were analyzed using a dedicated freeware tool developed by the first author ( www.icp-analyzer.org ). ICP data were given as mean values (SD) in mmHg. Test-retest validity was assessed using Pearson´s correlation analysis. Results We evaluated 66 ICP data sets obtained repeatedly with a time difference of at least 24 hours under condition of unchanged valve settings in seven patients (1 male, 6 female). Implantation diagnoses were IIH (n=2), congenital hydrocephalus (n=2), normal pressure hydrocephalus (NPH) (n=1) and malresorptive hydrocephalus (n=2). Overall test re-test reliability was excellent (Pearsons correlation coefficient 0.99, p Conclusions We confirmed the high test-retest reliability of the standing-supine-sitting-paradigm for telemetric ICP measurements in the outpatient setting. The high test-retest reliability should be considered as pre-requisite for clinical decision making. We advocate the implementation and further testing of this method to validate its utility in guiding treatment decisions.

Despite a growing focus on content marketing as a modern marketing tool, research on it is sparse. Missing completely is a comparison of content marketing with other forms of content, namely sponsored and user-generated content, although these content types are of high relevance for the marketing strategy of a company. To fill this research gap, the present study examines how different content types are perceived and how they influence brand responses through persuasion knowledge. A serial mediation model is developed, which posits that different content types lead to a varying conceptual persuasion knowledge, which then influences the activation of attitudinal persuasion knowledge and in turn results in different brand attitudes. The corresponding model is tested in an experimental study, using different content types in the context of the video game industry. The findings indicate that, through the proposed serial mediation, sponsored content leads to a more negative brand attitude than user-generated content and content marketing. These results suggest that, although coming directly from a company, content marketing seemingly is perceived in a similar way as user-generated content. The implications for marketing managers concerning content marketing strategies are discussed.

A number of small middle-Neolithic (3300–2800 BC) settlements flourished in the Oldenburger Graben area of northern Germany. The excavations yielded large amounts of crop remains, suggesting that agrarian production was a cornerstone of subsistence economy. Until about 3000 BC, Oldenburger Graben was a fjord, which over time was separated from the Baltic Sea and became a lagoon. The location of the settlement in the wetlands would have been highly favourable, offering a range of terrestrial and aquatic resources. Nonetheless, it may have been challenging to the Neolithic farmers, as perhaps not much dry land was available for crop growing. The success of agrarian production likely depended on the methods employed. This is an initial attempt at reconstructing strategies of agricultural land use during the middle-Neolithic occupation of the Oldenburger Graben lowland. We combine information on the habitat preferences and life history of arable weeds, and the recently obtained carbon and nitrogen stable isotope values on crop grains from one of the sites. The evidence allows us to glean practices that crop cultivation may have entailed, including potential strategies aimed at improving productivity of arable land such as tillage, weeding and manuring. Although preliminary, the observations point at potentially different management of emmer and barley, perhaps due to their variable importance to the Neolithic residents. This is the first time that stable isotope analysis on crops from northern Germany is used to elucidate agricultural practices of the Funnelbeaker communities of the middle-Neolithic.

How did socio-cultural transformation processes change land-use patterns? Throughout the last 50 years, outstanding comprehensive geographic, archaeobiological, and archaeological data have been produced for the area of Oldenburger Graben, Schleswig-Holstein, Germany. Based on this exceptional data set, we are able to study the land-use patterns for a period ranging from the Final Mesolithic until the Late Neolithic (4600–1700 BCE). By application of fuzzy modeling techniques, these patterns are investigated diachronically in order to assess the scale of transformations between the different archaeological phases. Based on nutrient requirements and proposed dietary composition estimates derived from empirical archaeobotanical, archaeozoological, and stable isotope data, the required extent of the areas for different land-use practices are modeled. This information is made spatially explicit using a fuzzy model that reconstructs areas of potential vegetation and land-use for each transformation phase. Pollen data are used to validate the type and extent of land-use categories. The model results are used to test hypotheses on the dynamics of socio-cultural transformations: can we observe a diversification of land-use patterns over time or does continuity of land-use practices prevail? By integrating the different lines of evidence within a spatially explicit modeling approach, we reach a new quality of data analysis with a high degree of contextualization. This allows testing of hypotheses about Neolithic transformation processes by an explicit adjustment of our model assumptions, variables, and parameters.

Using projections of surface solar radiation and temperature from 23 CMIP5 global climate models for two climate change scenarios (RCP4.5 & 8.5) we quantify the average change in PV electricity production expected in the years 2060–2080 compared to the present (2007–2027). We upsample daily radiation data to hourly resolution with a sinusoidal diurnal cycle model and split it into direct and diffuse radiation with the semi-empirical BRL model as input to a PV electricity generation model. Locally, changes in PV potential from −6% to +3% in annual and −25% to +10% in monthly means are shown. These projections are combined with a PV deployment scenario and show countries benefitting from increased PV yields include Spain, France, Italy and Germany. We also calculate uncertainties when calculating PV yield with input data at daily or lower resolution, demonstrating that our method to derive synthetic hourly profiles should be of use for other researchers using input data with low temporal resolution. We conclude that PV is an attractive and no-regrets investment in Europe irrespective of future climate change, and can continue to play a key role in energy system decarbonisation.

High static power associated with static random access memory (SRAM) represents a bottleneck in increasing the amount of on-chip memory. Novel, emerging nonvolatile memories such as spin-transfer torque magnetic random access memory (STT-RAM), resistive random access memory (RRAM), and ferroelectric field effect transistor-based random access memory (FeFET-RAM) are alternatives for replacing hardware kernels such as SRAM-based last level caches (LLC) due to their fast access times and lower leakage. In this paper, we study an ultra-dense FeFET-RAM based on 1-FeFET memory cells, and address potential disturbance issues at the array level. Disturbances are studied experimentally and via simulation. Experimental measurements are well correlated with modeling results suggesting that we have a good understanding of how disturbance issues will manifest themselves. That said, previous WRITE schemes for 1-FeFET arrays may: 1) exacerbate disturbances and 2) significantly degrade figures of merit (FoM) such as WRITE power. To address these issues, we propose the use of columnwise body connections to simultaneously overcome disturbances and reduce leakage currents during WRITES. We present detailed studies on how 1-FeFET memory cells and arrays (with columnwise body bias) fare when compared to traditional SRAM approaches and other emerging technologies. Notably, we benchmark the 1-FeFET memory against 1T * 1FeFET and 2T * 1FeFET designs proposed in early works, as well as SRAM, STT-RAM, and RRAM. Our evaluation of a $64\times 64$ FeFET-RAM array shows that the area, READ delay, and static power are reduced by $\sim 5.3\times $ , $\sim 1.5\times $ , and $\sim 74\times $ , respectively, when compared to an SRAM equivalent. Also, the 1-FeFET memory cell design shows $\sim 50\times $ improvements in terms of WRITE energy with respect to STT-RAM and RRAM counterparts.

The difference in the switching behavior of program and erase operation in hafnium oxide based ferroelectric FETs (FeFETs) highlights insufficiency of models solely based on the ferroelectric hysteresis. In this work, program and erase characteristics across various FeFET dimensions have been compared in order to investigate the scaling-dependent switching behavior. A simulation model comprising the FeFET channel size, effective grain size, phase and orientation was developed to mimic the field controlled switching of ferroelectric grains and their effect on resulting current percolation paths. Finally, the impact of FET channel length L and width W was systematically analyzed both experimentally and using the developed model for both memory states. Investigations show how systematic W and L scaling can be utilized to tune switching behavior from abrupt digital-like, suitable for robust memory applications, to gradual analog-like, favorable in neuromorphic applications.

Introduction Diffusion-weighted imaging in stimulated echo acquisition mode (STEAM-DWI) is an interesting alternative with less susceptibility artifacts compared to the most commonly used diffusion-weighted echo-planar imaging (EPI-DWI). Sensitivity and specificity of a novel STEAM-DWI, described by Merrem et al. 2017 [1], were assessed in patients with ischemic stroke. Methods EPI- and STEAM-DWIs were performed in patients with suspected subacute stroke between 01 July 2019 and 30 June 2020 using 3-T MRI. Three neuroradiologists independently and separately rated STEAM-DWI images with respect to (i) signs of an acute/subacute stroke, (ii) the number, size and localization of infarctions and, (iii) the presence of artifacts. Results In 55 (23 right, 23 left, 9 both hemispheres) of 85 patients a subacute stroke was confirmed using EPI-DWI. The cerebral vascular territories were affected as follows: anterior cerebral artery 8 %, middle cerebral artery 48 %, posterior cerebral artery 27 %, brainstem 7 %, cerebellum 10 %. In 53 of 55 (96 %) cases the stroke was detected by usage of STEAM-DWI, in 35 of 37 patients microembolic events were noticed (95 %). Results showed a sensitivity and specificity of 100 % (70/70) for major infarcts (>9 mm² in-plane) and a sensitivity of up to 94 % (121/129) for detecting subacute microembolic lesions. No susceptibility artifacts were noticed in STEAM-DWI. Conclusion Compared to standard EPI-DWI, STEAM-DWI offers a more robust alternative for diagnosing subacute strokes in areas affected by susceptibility artifacts.

This paper presents a method that allows to improve the quality of ptycho- graphic reconstructions at a reduced dose by adaptively scanning the specimen and thus providing only local information redundancy in regions of highest importance.

Impairment of health after overcoming the acute phase of COVID-19 is being observed more and more frequently. Here different symptoms of neurological and/or cardiological origin have been reported. With symptoms, which are very similar to the ones reported but are not caused by SARS-CoV-2, the occurrence of functionally active autoantibodies ((f)AABs) targeting G-protein coupled receptors (GPCR-(f)AABs) has been discussed to be involved. We, therefore investigated, whether GPCR-(f)AABs are detectable in 31 patients suffering from different Long-COVID-19 symptoms after recovery from the acute phase of the disease. The spectrum of symptoms was mostly of neurological origin (29/31 patients), including post-COVID-19 fatigue, alopecia, attention deficit, tremor and others. Combined neurological and cardiovascular disorders were reported in 17 of the 31 patients. Two recovered COVID-19 patients were free of follow-up symptoms. All 31 former COVID-19 patients had between 2 and 7 different GPCR-(f)AABs that acted as receptor agonists. Some of those GPCR-(f)AABs activate their target receptors which cause a positive chronotropic effect in neonatal rat cardiomyocytes, the read-out in the test system for their detection (bioassay for GPCR-(f)AAB detection). Other GPCR-(f)AABs, in opposite, cause a negative chronotropic effect on those cells. The positive chronotropic GPCR-(f)AABs identified in the blood of Long-COVID patients targeted the β(2)-adrenoceptor (β(2)-(f)AAB), the α1-adrenoceptor (α(1)-(f)AAB), the angiotensin II AT1-receptor (AT1-(f)AAB), and the nociceptin-like opioid receptor (NOC-(f)AAB). The negative chronotropic GPCR-(f)AABs identified targeted the muscarinic M(2)-receptor (M(2)-(f)AAB), the MAS-receptor (MAS-(f)AAB), and the ETA-receptor (ETA-(f)AAB). It was analysed which of the extracellular receptor loops was targeted by the autoantibodies.

Radiation-induced late side effects such as cognitive decline and normal tissue complications can severely affect quality of life and outcome in long-term survivors of brain tumors. Proton therapy offers a favorable depth-dose deposition with the potential to spare tumor-surrounding normal tissue, thus potentially reducing such side effects. In this study, we describe a preclinical model to reveal underlying biological mechanisms caused by precise high-dose proton irradiation of a brain subvolume. We studied the dose- and time-dependent radiation response of mouse brain tissue, using a high-precision image-guided proton irradiation setup for small animals established at the University Proton Therapy Dresden (UPTD). The right hippocampal area of ten C57BL/6 and ten C3H/He mice was irradiated. Both strains contained four groups (nirradiated = 3, ncontrol = 1) treated with increasing doses (0 Gy, 45 Gy, 65 Gy or 85 Gy and 0 Gy, 40 Gy, 60 Gy or 80 Gy, respectively). Follow-up examinations were performed for up to six months, including longitudinal monitoring of general health status and regular contrast-enhanced magnetic resonance imaging (MRI) of mouse brains. These findings were related to comprehensive histological analysis. In all mice of the highest dose group, first symptoms of blood-brain barrier (BBB) damage appeared one week after irradiation, while a dose-dependent delay in onset was observed for lower doses. MRI contrast agent leakage occurred in the irradiated brain areas and was progressive in the higher dose groups. Mouse health status and survival corresponded to the extent of contrast agent leakage. Histological analysis revealed tissue changes such as vessel abnormalities, gliosis, and granule cell dispersion, which also partly affected the non-irradiated contralateral hippocampus in the higher dose groups. All observed effects depended strongly on the prescribed radiation dose and the outcome, i.e. survival, image changes, and tissue alterations, were very consistent within an experimental dose cohort. The derived dose–response model will determine endpoint-specific dose levels for future experiments and may support generating clinical hypotheses on brain toxicity after proton therapy.

Subjective Logic (SL) is a powerful extend of classical probability theory that can handle small sample sizes and, with that, the resulting statistical uncertainty. However, SL is a quite abstract theory and has found limited attention in the field of automation so far. In this work, we present a new urn model intuition to SL that connects SL with the P��lya urn scheme. The application of SL-based reliability estimation in automation is demonstrated on two examples from the domain of connected automated driving: first to assess external information for motion planning on-board the vehicle and second to rate connected vehicles as agents within a large-scale multi-agent system., publishedVersion

The DePFET is an active pixel sensor utilized or suggested for several experiments. For future applications, it is desirable to improve the signal to noise ratio of the DePFET. The DePFET is essentially a pMOSFET built on a high resistive, fully depleted bulk. A deep-n implant beneath the MOS-gate forms a positive potential. Electrons collected in this internal gate modulate the transistors conductivity. This charge gain is influenced by the geometry and operational parameters of the DePFET. To study all influences, we utilized Sentaurus TCAD based simulations to investigate the DePFETs characteristics and compared the results from simulations and measurements. Using the simulations, we studied possible improvements of the DePFET, optimizing its charge gain and noise. From these simulations, it becomes evident, that especially impact ionization poses a problem. We developed an optimized technology that can overcome this limitation.

We report on antiferroelectric (AFE) hybrid charge trap (CT) memory with amplified tunnel oxide field via dynamic AFE hysteresis dipole switching. Memory window (4.5V), switching speed (

Autonomous vehicles need precise knowledge on dynamic objects in their surroundings. Especially in urban areas with many objects and possible occlusions, an infrastructure system based on a multi-sensor setup can provide the required environment model for the vehicles. Previously, we have published a concept of object reference points (e.g. the corners of an object), which allows for generic sensor "plug and play" interfaces and relatively cheap sensors. This paper describes a novel method to additionally incorporate multiple hypotheses for fusing the measurements of the object reference points using an extension to the previously presented Labeled Multi-Bernoulli (LMB) filter. In contrast to the previous work, this approach improves the tracking quality in the cases where the correct association of the measurement and the object reference point is unknown. Furthermore, this paper identifies options based on physical models to sort out inconsistent and unfeasible associations at an early stage in order to keep the method computationally tractable for real-time applications. The method is evaluated on simulations as well as on real scenarios. In comparison to comparable methods, the proposed approach shows a considerable performance increase, especially the number of non-continuous tracks is decreased significantly.

Corona virus disease 2019 (COVID-19) is a respiratory disease caused by a new coronavirus (SARS-CoV-2) which causes significant morbidity and mortality. The emergence of this novel and highly pathogenic SARS-CoV-2 and its rapid international spread poses a serious global public health emergency. To date 32,174,627 cases, of which 962,613 (2.99%) have died, have been reported (https://www.who.int/westernpacific/health-topics/coronavirus, accessed 23 Sep 2020). The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. There are still not many SARS-CoV-2-specific and effective treatments or vaccines available. A second round of infection is obviously unavoidable. Aptamers had already been at the centre of interest in the fight against viruses before now. The selection and development of a new aptamer is, however, a time-consuming process. We therefore checked whether a clinically developed aptamer, BC 007, which is currently in phase 2 of clinical testing for a different indication, would also be able to efficiently bind DNA-susceptible peptide structures from SARS-CoV-2-spreading crucial proteins, such as the receptor binding domain (RBD) of the spike protein and the RNA dependent RNA polymerase of SARS-CoV-2 (re-purposing). Indeed, several such sequence-sections have been identified. In particular for two of these sequences, BC 007 showed specific binding in a therapy-relevant concentration range, as shown in Nuclear magnetic resonance (NMR)- and Circular dicroism (CD)-spectroscopy and isothermal titration calorimetry (ITC). The excellent clinical toxicity and tolerability profile of this substance opens up an opportunity for rapid clinical testing of its COVID-19 effectiveness., Antiviral; Aptamer; BC 007; COVID-19; Re-purposing; SARS-CoV-2; Pharmaceutical science; Health sciences; Infectious disease; Pharmacology; Clinical research.

Automated vehicles need to not only perceive their environment, but also predict the possible future behavior of all detected traffic participants in order to safely navigate in complex scenarios and avoid critical situations, ranging from merging on highways to crossing urban intersections. Due to the availability of datasets with large numbers of recorded trajectories of traffic participants, deep learning based approaches can be used to model the behavior of road users. This paper proposes a convolutional network that operates on rasterized actor-centric images which encode the static and dynamic actor-environment. We predict multiple possible future trajectories for each traffic actor, which include position, velocity, acceleration, orientation, yaw rate and position uncertainty estimates. To make better use of the past movement of the actor, we propose to employ temporal convolutional networks (TCNs) and rely on uncertainties estimated from the previous object tracking stage. We evaluate our approach on the public "Argoverse Motion Forecasting" dataset, on which it won the first prize at the Argoverse Motion Forecasting Challenge, as presented on the NeurIPS 2019 workshop on "Machine Learning for Autonomous Driving"., acceptedVersion

Background For prostate cancer, signaling pathways induced by over-boarding stimulation of G-protein coupled receptors (GPCR) such as the endothelin, α1- and β-adrenergic, muscarinic and angiotensin 1 receptors were accused to support the carcinogenesis. However, excessive receptor stimulation by physiological receptor ligands is minimized by a control system that induces receptor sensitization and down-regulation. This system is missing when so-called “functional autoantibodies” bind to the GPCR (GPCR-AAB). If GPCR-AAB were found in patients with prostate cancer, uncontrolled GPCR stimulation could make these autoantibodies an additional supporter in prostate cancer. Methods Using the bioassay of spontaneously beating cultured rat neonatal cardiomyocytes, GPCR-AAB were identified, quantified and characterized in the serum of 25 patients (aged 56–78 years, median 70 years) with prostate cancer compared to 10 male patients (aged 48–82 years, median 64) with urinary stone disorders (controls). Results Of the cancer patients, 24 (96%) and 17 (68%), respectively, carried autoantibodies directed against the α1-adrenergic receptor (α1-AAB) and endothelin receptor A (ETA-AAB). No patient was negative for both GPCR-AAB. In contrast, ETA-AAB and α1-AAB were absent in all (100%) and 9 (90%) of the 10 control patients, respectively. While α1-AAB targeted a specific epitope of the first extracellular loop of the α1-adrenergic receptor subtype A, an epitope of the second extracellular loop of the ETA receptor was identified as a target of ETA-AAB. As demonstrated in vitro, the functional activity of both autoantibodies found in prostate cancer can be neutralized by the aptamer BC007. Conclusions We hypothesized that α1-AAB and ETA-AAB, which are highly present in prostate cancer patients, could by their functional activity support carcinogenesis by excessive receptor stimulation. The in vitro demonstrated neutralization of α1- and ETA-AAB by the aptamer BC007 could open the door to complement the treatments already available for prostate cancer.

Self-assessment is a key to safety and robustness in automated driving. In order to design safer and more robust automated driving functions, the goal is to self-assess the performance of each module in a whole automated driving system. One crucial component in automated driving systems is the tracking of surrounding objects, where the Kalman filter is the most fundamental tracking algorithm. For Kalman filters, some classical online consistency measures exist for self-assessment, which are based on classical probability theory. However, these classical approaches lack the ability to measure the explicit statistical uncertainty within the self-assessment, which is an important quality measure, particularly, if only a small number of samples is available for the self-assessment. In this work, we propose a novel online self-assessment method using subjective logic, which is a modern extension of probabilistic logic that explicitly models the statistical uncertainty. Thus, by embedding classical Kalman filtering into subjective logic, our method additionally features an explicit measure for statistical uncertainty in the self-assessment., Accepted for presentation at the 2020 IEEE 23rd International Conference on Information Fusion (FUSION), July 6 - 9, 2020, Virtual Conference

A Novel MFMFIS FeFET based on dual MFM/MFIS integration in a single gate stack is reported. The external top and bottom contacts, dual ferroelectric (FE) layers, and tailored MFM/MFIS area ratio $(\mathrm{A}_{\mathrm{FI}})$ shows flexible stack tuning for improved FeFET performance. A tradeoff between maximized MFM voltage and weaker FET channel inversion is notable in the ID(sat) as AFI decreases. A dual FE layer enables maximized MW and fine control of its size when MFM/MFIS switching contribution is tuned through AFI change. The merits of $\mathrm{A}_{\mathrm{FI}}$ tuning extends to low voltage switching with maximized MW size and extremely linear current change over a wide dynamic range at high symmetry of synaptic potentiation/depression. Reliability in terms of variability, temperature effects, endurance, and retention is reported. The MFMFIS concept is thoroughly discussed with insight on optimal stack tuning for improved FeFET characteristics.

Since David Chaum introduced the idea of mix nets 40 years ago, they have become widely used building blocks for privacy-preserving protocols. Several important applications, such as secure e-voting, require that the employed mix net be verifiable. In the literature, numerous techniques have been proposed to make mix nets verifiable. Some of them have also been employed in politically binding elections. Verifiable mix nets differ in many aspects, including their precise verifiability levels, possible trust assumptions, and required cryptographic primitives; unfortunately, these differences are often opaque, making comparison painful. To shed light on this intransparent state of affairs, we provide the following contributions. For each verifiability technique proposed to date, we first precisely describe how the underlying basic mix net is to be extended and which (additional) cryptographic primitives are required, and then study its verifiability level, including possible trust assumptions, within one generic and expressive verifiability framework. Based on our uniform treatment, we are able to transparently compare all known verifiability techniques for mix nets, including their advantages and limitations. Altogether, our work offers a detailed and expressive reference point for the design, employment, and comparison of verifiable mix nets. © 2020 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.

With the discovery of ferroelectricity in HfO 2 based thin films and the co-integration of ferroelectric field effect transistors (FeFET) into standard high-k metal gate (HKMG) CMOS platforms, the FeFET has emerged from a theoretical dream to an applicable reality. This paper summarizes the status of GLOBALFOUNDRIES FeFET technology and some of its potential applications. We show excellent 0.12µm2 SRAM yields of our mature 28nm CMOS platform, with co-integrated FeFETs, exhibiting a solid memory window of 1.4V. In contrast to conventional embedded memory cells, the FeFET can be integrated like a regular 26A EOT transistor, exhibiting two reversibly programmable VT states, while offering full design flexibility. We show state of the art across wafer VT variability of the programmed and erased states of the FeFETs and discuss its layout-dependence. Embedded size-competitive FeFETs already allow solid separation of the memory states, approaching a mature 6Sigma distribution. Reasonable endurance and stable data retention are demonstrated. Moreover, an outlook of this technology beyond the von Neumann computing will be discussed, considering some of the various applications of this new, versatile device.

Improved characteristics of ferroelectric Si:HfO 2 (HSO) MFIS FeFETs by tuning the substrate implant doping concentration is reported. Shallow implant doping gives the possibility to control the FeFET readout range, whereas the deep implant affects the I off current, resulting in a higher I on -I off current ratio. Additionally, the implant tuning improves the switching MFIS field distribution enabling lower FeFET switching voltages. A transition from a charge trap dominated endurance to an endurance that is limited by the interface trap generation is observed when the substrate implant is tuned. An endurance of 105 cycles with approximately 4 orders of magnitude I on -I off residual current ratio is measured on the FeFET devices. The impact of tuning shallow and deep substrate implant profiles is studied with respect to changes of the MFIS stack characteristics and overall FeFET performance.

The impact of the ferroelectric (FE) wakeup phenomenon on the reliability of fluorite structure-based laminated Si-doped hafnium oxide (HSO) FeFET memory cells is reported. The post wakeup cycling shows a strong change in the optimal program/erase (PG/ER) write conditions. A shift towards lower PG/ER switching conditions at a higher memory window (MW) is observed after wakeup cycling. Similarly, the cross wafer statistics for different FeFET dimensions shows a strong wakeup influence towards a lower variability and higher MW after wakeup. For the wakeup cycling different trends for amplitude and pulse width variation are observed. The increase in write pulse amplitude has limited impact whereas the number of wakeup cycles appears to be the driving factor. On the contrary, the write pulse width sweep (50-800ns) shows faster wakeup as the pulse width increases even on pristine devices. The FeFET area sweep shows a comparable wakeup behavior with a trend of higher shift window on larger devices. The high-temperature operation shows an initially lower MW and pronounced wakeup effect. On the other hand, the pyroelectric effect dominates at lower temperatures and leads to initially higher MW with an insignificant wakeup. The various factors associated with the FE wakeup effect are studied with insight into the changes in FeFET stack physics during wakeup cycling.

Increasing demands for new computer architectures may require embedded non-volatile memories as for example in-memory computing. Ferroelectric field-effect transistors (FeFETs) add further advantages besides their outstanding properties due to the availability of both n-type and p-type transistors. The latter favor a different channel materials, like SiGe, due to the low hole mobility in silicon. In this article, we demonstrate the integration of ferroelectric hafnium oxide on SiGe as well as working p-type FeFETs, possessing a large memory window of about 1.1 V and low variability. Such architectures were co-integrated into a standard high-k metal gate (HKMG) CMOS platform. Furthermore, we report on the impact of annealing temperature on the interface and ferroelectric layer, which appears to be universal for SiGe and Si substrates. Here, a growth of the interface layer during annealing at higher temperatures was observed as well as a reduction of the wake-up effect for the ferroelectric layer.

Inverse problems in image processing, phase imaging, and computer vision often share the same structure of mapping input image(s) to output image(s) but are usually solved by different application-specific algorithms. Deep convolutional neural networks have shown great potential for highly variable tasks across many image-based domains, but sometimes can be challenging to train due to their internal non-linearity. We propose a novel, fast-converging neural network architecture capable of solving generic image(s)-to-image(s) inverse problems relevant to a diverse set of domains. We show this approach is useful in recovering wavefronts from direct intensity measurements, imaging objects from diffusely reflected images, and denoising scanning transmission electron microscopy images, just by using different training datasets. These successful applications demonstrate the proposed network to be an ideal candidate solving general inverse problems falling into the category of image(s)-to-image(s) translation.