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Coastal ecosystems are vulnerable to climate change, with rising sea levels and increased anthropogenic pressure constraining space for natural processes. Nature based solutions using sediments rather than hard surfaces in coastal defense may offer an alternative that both creates new habitats and offer a flexible protection against flooding.In contrast to hard infrastructure, the topography of dunes depends on the highly dynamic processes of wind and waves and the resistance to them offered by dune vegetation. Perennial grass species such as marram grass (Ammophila arenaria) and sand couch (Elytrigia juncea) play a key-role for topographic stability and the development and shape of coastal dune forms. This is usually attributed to their dense cover which effectively traps sand as well as their positive growth response to burial by sediments. Therefore, species like marram grass have been used as ecosystem engineers in both past and recent coastal dune restoration projects.Whether this solution will be applicable in the future depends on climate change. Coastal vegetation is vulnerable to climate change due to its susceptibility to changes in growing conditions (e.g. Temperature, Precipitation). Especially at the dry-beach section where the influence of groundwater is limited, a change in growing season precipitation could potentially affect the cover of dune grasses. Past research was already able to establish a general link between dune development and growth in function of precipitation. However, to this date direct responses of dune vegetation to precipitation has not been quantified.We explored the response of dune building grasses to summer precipitation and its implication for the future dune building in a two-step approach. We used a greenhouse-experiment to derive species growth relationships with water availability for marram grass and sand couch. In a second step we used these relationships to explore the impact of potential changes in summer precipitation on the growth of these species. We found that both marram grass and sand couch were equally sensitive to changes in water availability and responded positively to an increase in it. Comparing soil moisture from the field to the greenhouse, showed that field water availability tended to be on the lower end of ranges in the greenhouse. This suggests that dune vegetation in the field is susceptible to drought effects. Exploring these results further using climate scenarios, we found that plant growth was increased by 1.3 % (experimental period) – 1.8 % (extrapolated) under the most recent RCP 4.5 IPCC projection and by 9.6 – 13 % for an extremely wet year. In contrast, for an extremely dry year plant growth could decrease by 6.2 – 8.2 %.While changes of < 2 % in plant growth might have limited implications for dune development and stability, years of extreme climate conditions show a bigger range in plant growth (- 8 % - + 13 %) which is more likely to also have direct consequences for dune growth and development. Incorporating these relationships between plant growth and climate in models of coastal dune development should improve predictions of climate change impacts.

Sandy shores serve a multitude of purposes; they protect the inland from flooding, support a high biodiversity, and are recreation hotspots. To what extent these functions can coexist or are mutually exclusive is unclear, especially given increasing stressors such as rising sea levels and urbanization. Knowledge on the trade-offs between these functions is important when designing these areas and nature-based solutions to ensure the desired results. We investigated the effect of recreational pressure on the establishment of two common dune building grass species (Ammophila arenaria and Elytrigia juncea). We conducted a field introduction experiment with seeds and rhizomes of both species along increasing distance to a beach entrance. We established a total of 300 plots, following a randomised block design with 4 factorial treatments (species * type diaspore) and 60 replicates for two beaches on the Dutch barrier Island of Terschelling. Plant material was collected from the wild, using local genetic material. Plant seeds were left in their husk to mimic natural dispersal. Plots were georeferenced by means of Real Time Kinematic and left unmarked to enable undisturbed recreation. Recreation pressure was assessed by counting the number of people at different beach sections, confirming that anthropogenic pressure increased with distance to the beach entrance. Establishment success was monitored by counting the number of emerged seeds and sprouted rhizomes per plot at regular intervals across the growing season. To control for drivers other than recreation pressure, we also monitored environmental variables, such as the change in beach level. Preliminary results suggest that environmental factors such as erosion and burial are limiting the establishment success for all treatments. Moreover, a positive effect of distance from the entrance on the establishment success of both species can be observed. This is especially clear within the first 100 meters. The strongest effect seems to be for Ammophila arenaria. These preliminary results indicate that both sediment dynamics and recreational pressure play a role in the new establishment of these species on the upper beach. This means that the impact of both should be considered when designing sandy coastal areas.

Supplementary Figure 1 from Methylation-Independent Silencing of the Tumor Suppressor INK4b (p15) by CBFβ-SMMHC in Acute Myelogenous Leukemia with inv(16)

Supplementary Figure 1 Legend from Methylation-Independent Silencing of the Tumor Suppressor INK4b (p15) by CBFβ-SMMHC in Acute Myelogenous Leukemia with inv(16)

Supplementary Tables 1-2 from Methylation-Independent Silencing of the Tumor Suppressor INK4b (p15) by CBFβ-SMMHC in Acute Myelogenous Leukemia with inv(16)

The tumor suppressor gene INK4b (p15) is silenced by CpG island hypermethylation in most acute myelogenous leukemias (AML), and this epigenetic phenomenon can be reversed by treatment with hypomethylating agents. Thus far, it was not investigated whether INK4b is hypermethylated in all cytogenetic subtypes of AML. A comparison of levels of INK4b methylation in AML with the three most common cytogenetic alterations, inv(16), t(8;21), and t(15;17), revealed a strikingly low level of methylation in all leukemias with inv(16) compared with the other types. Surprisingly, the expression level of INK4b in inv(16)+ AML samples was low and comparable with that of the other subtypes. An investigation into an alternative mechanism of INK4b silencing determined that the loss of INK4b expression was caused by inv(16)-encoded core binding factor β-smooth muscle myosin heavy chain (CBFβ-SMMHC). The silencing was manifested in an inability to activate the normal expression of INK4b RNA as shown in vitamin D3–treated U937 cells expressing CBFβ-SMMHC. CBFβ-SMMHC was shown to displace RUNX1 from a newly determined CBF site in the promoter of INK4b. Importantly, this study (a) establishes that the gene encoding the tumor suppressor p15INK4b is a target of CBFβ-SMMHC, a finding relevant to the leukemogenesis process, and (b) indicates that, in patients with inv(16)-containing AML, reexpression from the INK4b locus in the leukemia would not be predicted to occur using hypomethylating drugs. [Cancer Res 2007;67(3):992–1000]

Diese Arbeit konzentriert sich auf die Untersuchung des Einflusses von verschiedenen Promotoren wie Kalium, Aluminium und Magnesium auf Makro- und Nanostruktur, Zusammensetzung, Reduktionsverhalten und katalytische Aktivität von eisenbasierten Modellkatalysatoren für die Ammoniaksynthese mithilfe von verschiedenen Charakterisierungsmethoden wie Elektronenmikroskopie, Röntgendiffraktometrie und Physisorptionsexperimenten und katalytischen Tests unter industriell relevanten Bedingungen. Die verwendeten Modellkatalysatoren wurden aus der Reduktion von zwei verschiedenen Klassen von alternativen Präkursormaterialien gewonnen. Als Präkursormaterialien verwendet wurden zum einen Eisen(III)-hydroxidoxid (FeOOH) Nanoplättchen und zum anderen nanostrukturierte Magnesioferrite (\(MgFe_{2}O_{4}\)), wobei die Magnesioferrite mithilfe einer Syntheseroute über einer "Layered double hydroxide" Phase hergestellt wurden.

Cysteine proteases obtained from the stem of pineapple or papaya latex, bromelain and papain, respectively, exhibit a broad spectrum of beneficial effects on human health. However, their effects on gut microbiota composition or dose-manner effects on the intestinal integrity of healthy tissue have not been evaluated. In this study, C57BL/6 young, healthy mice were fed bromelain or papain in a dose of 1 mg per animal/day for three consecutive days, followed by the assessment of digestive protein capacity, intestinal morphology and gut microbiota composition. Furthermore, a human reconstructed 3D tissue model EpiIntestinal (SMI-100) was used to study the effects of 1, 0.1 and 10 mg/mL doses of each enzyme on tissue integrity and mucosal permeability using TEER measurements and passage of Lucifer Yellow marker from the apical to the basolateral side of the mucosa. The results indicated that fruit proteases have the potential to modulate gut microbiota with decreasing abundance of Proteobacteria and increasing beneficial Akkermansia muciniphila. The enhancement of pancreatic trypsin was observed in bromelain and papain supplementation, while bromelain also increased the thickness of the ileal mucosa. Furthermore, an in vitro study showed a dose-dependent interruption in epithelial integrity, which resulted in increased paracellular permeability by the highest doses of enzymes. These findings define bromelain and papain as promising enzymatic supplementation for controlled enhancement of paracellular uptake when needed, together with beneficial effects on the gut microbiota.

Cysteine proteases obtained from the stem of pineapple or papaya latex, bromelain and papain, respectively, exhibit a broad spectrum of beneficial effects on human health. However, their effects on gut microbiota composition or dose-manner effects on the intestinal integrity of healthy tissue have not been evaluated. In this study, C57BL/6 young, healthy mice were fed bromelain or papain in a dose of 1 mg per animal/day for three consecutive days, followed by the assessment of digestive protein capacity, intestinal morphology and gut microbiota composition. Furthermore, a human reconstructed 3D tissue model EpiIntestinal (SMI-100) was used to study the effects of 1, 0.1 and 10 mg/mL doses of each enzyme on tissue integrity and mucosal permeability using TEER measurements and passage of Lucifer Yellow marker from the apical to the basolateral side of the mucosa. The results indicated that fruit proteases have the potential to modulate gut microbiota with decreasing abundance of Proteobacteria and increasing beneficial

Funder: European and Developing Countries Clinical Trials Partnership (EDCTP); doi: https://doi.org/10.13039/501100001713, Funder: MRC Centre for Global Infectious Disease Analysis (MR/R015600/1), jointly funded by the U.K. Medical Research Council (MRC) and the U.K. Foreign, Commonwealth and Development Office (FCDO), under the MRC/FCDO Concordat agreement. Community Jameel. The UK Research and Innovation (MR/V038109/1), the Academy of Medical Sciences Springboard Award (SBF004/1080), The MRC (MR/R015600/1), The BMGF (OPP1197730), Imperial College Healthcare NHS Trust- BRC Funding (RDA02), The Novo Nordisk Young Investigator Award (NNF20OC0059309) and The NIHR Health Protection Research Unit in Modelling Methodology. S. Bhatt thanks Microsoft AI for Health and Amazon AWS for computational credits., Funder: EA Funds, Funder: University of Oxford (Oxford University); doi: https://doi.org/10.13039/501100000769, Funder: DeepMind, Funder: OpenPhilanthropy, Funder: UKRI Centre for Doctoral Training in Interactive Artificial Intelligence (EP/S022937/1), Funder: Augustinus Fonden (Augustinus Foundation); doi: https://doi.org/10.13039/501100004954, Funder: Knud Højgaards Fond (Knud Højgaard Fund); doi: https://doi.org/10.13039/501100009938, Funder: Kai Lange og Gunhild Kai Langes Fond (Kai Lange and Gunhild Kai Lange Foundation); doi: https://doi.org/10.13039/501100008206, Funder: Aage og Johanne Louis-Hansens Fond (Aage and Johanne Louis-Hansen Foundation); doi: https://doi.org/10.13039/501100010344, Funder: William Demant Foundation, Funder: Boehringer Ingelheim Fonds (Stiftung für medizinische Grundlagenforschung); doi: https://doi.org/10.13039/501100001645, Funder: Imperial College COVID-19 Research Fund, Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289, European governments use non-pharmaceutical interventions (NPIs) to control resurging waves of COVID-19. However, they only have outdated estimates for how effective individual NPIs were in the first wave. We estimate the effectiveness of 17 NPIs in Europe’s second wave from subnational case and death data by introducing a flexible hierarchical Bayesian transmission model and collecting the largest dataset of NPI implementation dates across Europe. Business closures, educational institution closures, and gathering bans reduced transmission, but reduced it less than they did in the first wave. This difference is likely due to organisational safety measures and individual protective behaviours—such as distancing—which made various areas of public life safer and thereby reduced the effect of closing them. Specifically, we find smaller effects for closing educational institutions, suggesting that stringent safety measures made schools safer compared to the first wave. Second-wave estimates outperform previous estimates at predicting transmission in Europe’s third wave.

Aluminum is an element found in nature and in cosmetic products. It can interfere with the metabolism of other cations, thus inducing gastrointestinal disorder. In cosmetics, aluminum is used in antiperspirants, lipsticks, and toothpastes. The aim of this work is to investigate aluminum bioavailability after accidental oral ingestion derived from the use of a toothpaste containing a greater amount of aluminum hydroxide than advised by the Scientific Committee on Consumer Safety (SCCS). To simulate in vitro toothpaste accidental ingestion, the INFOGEST model was employed, and the amount of aluminum was measured through the ICP-AES analysis. Tissue barrier integrity was analyzed by measuring transepithelial electric resistance, and the tissue architecture was checked through light microscopy. The margin of safety was also calculated. Overall, our results indicate that the acute exposure to aluminum accidentally ingested from toothpastes is safe for the final user, even in amounts higher than SCCS indications.

Hereditary breast and ovarian cancer (HBOC) is primarily associated with mutations in the BRCA1/2 genes. However, causal variants in other high, moderate, and low penetrance genes proportionally increase the risk of breast/ovarian cancer. This study aims to provide data about the mutation spectrum of HBOC-associated genes in Slovak HBOC families and estimate the ratio of BRCA versus non-BRCA causal variants. We used panel sequencing containing 22 high/moderate-risk susceptibility genes and parallel MLPA analysis of BRCA1/2, CHEK2 genes, to analyze 94 individuals with a strong family/personal history of breast and/or ovarian cancer. The analyzed group consisted of 80 patients diagnosed with cancer (85.1%) and 14 healthy individuals (14.9%) with a positive family history of HBOC syndrome. In total, we have identified 22 causal DNA variants (23.4%) showing 15 primary findings in BRCA1/2 genes (68.2%) and 7 positive secondary findings in CHEK2, PALB2, CDH1, and MUTYH genes (31.8%). The most frequent pathogenic alterations were BRCA1 mutations c.181T>G and CNV variant (c.5573-?_c.5701+?)del, known as deletion of exons 21-22. Besides known mutations, the BRCA1 variant c.2794del (p.Val932Leufs*68) and variant c.2480dup (p.Tyr827*) in the CDH1 gene represent the novel, previously unpublished variants that might be population-specific. In conclusion, we provide the first report of multigene panel testing in Slovak HBOC families demonstrating that almost one-third of pathogenic mutations are situated in susceptibility genes other than BRCA1/2. Although multigene panel testing requires precise data filtration and interpretation, it might bring the relevant data for clinical management of the patients.

We experimentally demonstrate excitation of orbital angular momentum states in an air-core fiber by a silicon integrated vortex beam emitter which is designed and fabricated to match the modes supported by the fiber. The coupling loss is measured to be ∼7.5 dB. Excitation of eigenmodes is confirmed by analyzing the fiber output.

Menschen mit komplexen Kommunikationsbedürfnissen sind – wie alle anderen Menschen auch – grundlegend auf Beziehungen und Kommunikation angewiesen. Um sie in ihrer Kommunikation wirksam unterstützen zu können, schlägt dieses Buch eine Brücke zwischen Theorie, Empirie und unmittelbarer Praxis der Unterstützten Kommunikation. Im Fokus des Lehrbuches stehen dabei sowohl die Einzelpersonen mit ihren jeweiligen Kommunikationsbedürfnissen als auch deren gesamtes Umfeld. Die Autoren liefern fundiertes Wissen über Kommunikationsmodelle, Unterstützte Kommunikation, deren Anwendung und stellen praktische Hilfen für die Unterstützte Kommunikation vor. LeserInnen erfahren, wie Maßnahmen zur Kommunikationsunterstützung sinnvoll durchgeführt, begleitet, überprüft und dokumentiert werden können.

Bakalaureusetöö Tehnika ja tehnoloogia õppekaval Lõputöö teema valiti seoses autori hobist kardispordi vastu ning huvist sisepõlemismootori vastu. Käesoleva bakalaureusetöö eesmärk on leida sissepritsesüsteemi lahendus kahetaktilisele mootorile. Töö esimeses peatükis kirjeldatakse kahetaktilise mootori tööpõhimõtet ning mootori komponente. Teises peatükis kirjeldatakse sissepritse liike ja nende tunnuseid ja küttesegu moodustamist. Kolmandas peatükis viiakse läbi turu-uuring ning neljandas leitakse valitud mootorile sissepritsesüsteemi lahendus. The topic of the thesis was chosen in connection with the author's hobby of karting and his interest in the internal combustion engine. The aim of this bachelor's thesis is to find an injection system solution for a two-stroke engine. The first chapter describes the operation of a two-stroke engine and engine components. The second chapter describes the types of injection and their characteristics and the formation of the fuel mixture. In the third chapter, a market study is carried out and in the fourth, an injection system solution is found for the selected engine.

Masculinity has been and continues to be of fundamental importance to Islamist movements, including the relatively distinct Turkish variety. The article offers a broad analysis of various aspects of Islamist masculinity in Turkey. It begins by examining how, from the 1950s onwards, Islamic intellectuals there conceived of a new political subjectivity based on an ideal masculinity. After a discussion of Islamist masculinity drawing on novels, manuals and other sources, the article demonstrates how everyday social practices (such as clothing and beards, or an interest in poetry) established further facets of Islamist masculinity. Turkish Islamism organised itself in the Milli Görüş movement beginning in the 1970s and rose to become a mass movement in the 1980s. Against this background, a new masculinity could be construed as a way out of the self-perceived inferiority to the West. In social practice, this masculinity was transformed by increasingly rigid rules of behaviour and the establishment of a distinct habitus of pathos and discipline, which is then analysed in conclusion. Männlichkeit war und ist von grundlegender Bedeutung für islamistische Bewegungen, so auch für die relativ eigenständige türkische Variante. Der Aufsatz bietet eine breite Analyse verschiedener Aspekte islamistischer Männlichkeit in der Türkei. Zunächst wird untersucht, wie islamische Intellektuelle dort ab den 1950er-Jahren basierend auf einer idealen Männlichkeit eine neue politische Subjektivität konzipierten. Nach einer Auseinandersetzung mit islamistischer Männlichkeit im Diskurs anhand von Quellen wie Romanen und Ratgebern wird dargelegt, wie alltägliche gesellschaftliche Praktiken (etwa Kleidung oder Bärte, aber auch das Interesse an Poesie) weitere Facetten islamistischer Männlichkeit etablierten. Der türkische Islamismus organisierte sich seit den 1970er-Jahren in der Bewegung Milli Görüş und stieg in den 1980er-Jahren zur Massenbewegung auf. Vor diesem Hintergrund konnte eine neue Männlichkeit als Ausweg aus der selbstdiagnostizierten Unterlegenheit zum Westen konstruiert werden. In der sozialen Praxis wandelte sich diese Männlichkeit durch immer rigidere Verhaltensregeln und die Etablierung eines eigenständigen Habitus aus Pathos und Disziplin, der abschließend analysiert wird.

Introduction slides for the poster session for the General Meeting of IEA Wind Task 32 on November 16th 2021. Each Early Stage Researcher (ESR) from LIKE presented their work on one slide at the beginning of the session.

BackgroundSeasonal affective disorder (SAD) is common and debilitating. The standard of care includes light therapy provided by a light box; however, this treatment is restrictive and only moderately effective. Advances in LED technology enable lighting solutions that emit vastly more light than traditional light boxes. Here, we assess the feasibility of BROAD (Bright, whole-ROom, All-Day) light therapy and get a first estimate for its potential effectiveness.MethodsPatients were randomly assigned to a treatment for four weeks; either a very brightly illuminated room in their home for at least six hours per day (BROAD light therapy) or 30 minutes in front of a standard 10,000 lux SAD light box. Feasibility was assessed by monitoring recruitment, adherence, and side effects. SAD symptoms were measured at baseline and after two and four weeks, with the Hamilton Depression Rating Scale-Seasonal Affective Disorders 29-items, self-report version.ResultsAll 62 patients who started treatment were available at four-week follow-up and no significant adverse effects were reported. SAD symptoms of both groups improved similarly and considerably, in line with previous results. Exploratory analyses indicate that a higher illuminance (lux) is associated with a larger symptom improvement in the BROAD light therapy group.ConclusionsBROAD light therapy is feasible and seems similarly effective as the standard of care while not confining the participants to 30 minutes in front of a light box. In follow-up trials, BROAD light therapy could be modified for increased illuminance, which would likely improve its effectiveness.

Radiale Diffusoren werden oft zur Be- und Entladung von Warm- und Heißwasserspeichern eingesetzt. Bei schlanken Speichern treten intensive Mischungseffekte, wenn das Fluid (Wärmeträger, Wasser) in den Speicher eintritt [1], [2], auf. Ein neuer Ansatz beschäftigt sich mit einer zusätzlichen Drallerzeugung [3], [4]. Dadurch soll der Schichtungsaufbau beziehungsweise die thermische Schichtung verbessert werden. Strömungssimulationen lieferten bereits vielversprechende Ergebnisse [4], [5]. Dieser zweiteilige Beitrag stellt weiterführende Untersuchungen beziehungsweise erste Ergebnisse vor, die mit einem Versuchsstand und dem Einsatz von Diffusormodellen gewonnen wurden. Im ersten Teil [6] erfolgte die Erläuterung von Grundlagen und die Beschreibung des Versuchsstandaufbaus. Der zweite Teil liefert eine detaillierte Vorstellung und Auswertung der experimentellen Ergebnisse.

During the pandemic, there has been ongoing and contentious debate around the impact of restrictive government measures to contain SARS-CoV-2 outbreaks, often termed ‘lockdowns’. We define a ‘lockdown’ as a highly restrictive set of non-pharmaceutical interventions against COVID-19, including either stay-at-home orders or interventions with an equivalent effect on movement in the population through restriction of movement. While necessarily broad, this definition encompasses the strict interventions embraced by many nations during the pandemic, particularly those that have prevented individuals from venturing outside of their homes for most reasons. The claims often include the idea that the benefits of lockdowns on infection control may be outweighed by the negative impacts on the economy, social structure, education and mental health. A much stronger claim that has still persistently appeared in the media as well as peer-reviewed research concerns only health effects: that there has been a large toll of death and disease attributable directly to government action against COVID-19, a toll larger than that of COVID-19 itself.1 2 The tagline for this claim is that “the cure is worse than the disease”.3 Here, we consider the claim that lockdowns cause more health harms than COVID-19 by examining their impacts on mortality, routine health services, global health programmes and suicide and mental health. We examine the evidence regarding whether government interventions are to blame for negative health consequences, or whether the lethality and infectiousness of SARS-CoV-2 is as much or more of a driver behind adverse health impacts. The grave harms from ineffectively mitigated epidemics have been clearly seen in places such as India and Brazil.4 Given the benefits from government intervention against COVID-19—slowing spread and preventing COVID-19 deaths—we explore whether the harms of lockdowns are likely to exceed the harms of COVID-19, or if the health harms sometimes attributed to lockdowns may instead be explained directly by the pandemic itself.

Mask-wearing has been a controversial measure to control the COVID-19 pandemic. While masks are known to substantially reduce disease transmission in healthcare settings [1–3], studies in community settings report inconsistent results [4–6].Investigating the inconsistency within epidemiological studies, we find that a commonly used proxy, government mask mandates, does not correlate with large increases in mask-wearing in our window of analysis. We thus analyse the effect of mask-wearing on transmission instead, drawing on several datasets covering 92 regions on 6 continents, including the largest survey of individual-level wearing behaviour (n=20 million) [7]. Using a hierarchical Bayesian model, we estimate the effect of both mask-wearing and mask-mandates on transmission by linking wearing levels (or mandates) to reported cases in each region, adjusting for mobility and non-pharmaceutical interventions.We assess the robustness of our results in 123 experiments spanning 22 sensitivity analyses. Across these analyses, we find that an entire population wearing masks in public leads to a median reduction in the reproduction number R of 25.8%, with 95% of the medians between 22.2% and 30.9%. In our window of analysis, the median reduction in R associated with the wearing level observed in each region was 20.4% [2.0%, 23.3%]1. We do not find evidence that mandating mask-wearing reduces transmission. Our results suggest that mask-wearing is strongly affected by factors other than mandates.We establish the effectiveness of mass mask-wearing, and highlight that wearing data, not mandate data, are necessary to infer this effect.

While seasonal variation has a known influence on the transmission of several respiratory viral infections, its role in SARS-CoV-2 transmission remains unclear. As previous analyses have not accounted for the implementation of non-pharmaceutical interventions (NPIs) in the first year of the pandemic, they may yield biased estimates of seasonal effects. Building on two state-of-the-art observational models and datasets, we adapt a fully Bayesian method for estimating the association between seasonality and transmission in 143 temperate European regions. We find strong seasonal patterns, consistent with a reduction in the time-variableRtof 42.1% (95% CI: 24.7% – 53.4%) from the peak of winter to the peak of summer. These results imply that the seasonality of SARS-CoV-2 transmission is comparable in magnitude to the most effective individual NPIs but less than the combined effect of multiple interventions.

The eco-efficiency of actual production processes is still one dominating research area in engineering. However, neglecting the environmental impacts of production equipment, technical building services and energy supply might lead to sub-optimization or burden-shifting and thus reduced effectiveness. As an established method used in sustainability management, Life Cycle Assessment aims at calculating the environmental impacts from all life cycle stages of a product or system. In order to cope with shortcomings of the static character of life cycle models and data gaps this approach combines Life Cycle Assessment with manufacturing system simulation. Therefore, the two life cycles of product and production system are merged to assess environmental sustainability on product level. Manufacturing simulation covers the production system and Life Cycle Assessment is needed to relate the results to the final product. This combined approach highlights the influences from dynamic effects in manufacturing systems on resulting life cycle impact from both product and production system. Furthermore, the importance of considering indirect peripheral equipment and its effects on the manufacturing system operation in terms of output and energy demands is underlined. The environmental flows are converted into impacts for the five recommended environmental impact categories. Thus, it can be demonstrate that Life Cycle Assessment can enhance the process simulation and help identify hot-spots along the life cycle. The combined methodology is applied for analysing a case study in fourteen scenarios for the integration of volatile energy sources into energy flexible manufacturing control.

As European governments face resurging waves of COVID-19, non-pharmaceutical interventions (NPIs) continue to be the primary tool for infection control. However, updated estimates of their relative effectiveness have been absent for Europe’s second wave, largely due to a lack of collated data that considers the increased subnational variation and diversity of NPIs. We collect the largest dataset of NPI implementation dates in Europe, spanning 114 subnational areas in 7 countries, with a systematic categorisation of interventions tailored to the second wave. Using a hierarchical Bayesian transmission model, we estimate the effectiveness of 17 NPIs from local case and death data. We manually validate the data, address limitations in modelling from previous studies, and extensively test the robustness of our estimates. The combined effect of all NPIs was smaller relative to estimates from the first half of 2020, indicating the strong influence of safety measures and individual protective behaviours--such as distancing--that persisted after the first wave. Closing specific businesses was highly effective. Gathering restrictions were highly effective but only for the strictest limits. We find smaller effects for closing educational institutions compared to the first wave, suggesting that safer operation of schools was possible with a set of stringent safety measures including testing and tracing, preventing mixing, and smaller classes. These results underscore that effectiveness estimates from the early stage of an epidemic are measured relative to pre-pandemic behaviour. Updated estimates are required to inform policy in an ongoing pandemic.

Rezension zu: Christopher Degelmann, Squalor. Symbolisches Trauern in der Politischen Kommunikation der Römischen Republik und Frühen Kaiserzeit. Potsdamer Altertumswissenschaftliche Beiträge, Band 61. Verlag Franz Steiner, Stuttgart 2018. 361 Seiten, 4 Schwarzweißabbildungen., Bonner Jahrbücher, Bd. 217.2017(2018): Bonner Jahrbücher

Pedestrian zones are increasing in lengths and the relevant authorities are aiming at introducing autonomous vehicles to such zones for different purposes like transportation vehicles, delivery vehicles and cleaning vehicles. As the name suggests, pedestrian zones are crowded by pedestrian having highest priority. Vehicles in such zones should take special care regarding the safety of the people. Unlimited situations can occur from the pedestrians. Hence, it becomes crucial to test such vehicles before deploying in real-world to ensure safety of the people and the environment. Therefore, there is a need to have a realistic behaviors of pedestrians in simulation for critical testing of autonomous vehicles. The major novelty in this paper is the generation of virtual pedestrians which avoid obstacles realistically and to provide a platform for accurate and easy testing of autonomous vehicles in pedestrian zones. These virtual pedestrians avoid all kinds of obstacles based on self-awareness while progressing towards the goal. Main feature of these pedestrians are based on direction and speed heuristics. The goal is to have minimum number of parameters to generate test scenarios with realistic behaving pedestrians for autonomous systems. A thorough experimentation is done to validate the system. In the final experiment, a real-world scene is recreated from the simulation and the results are compared. It is seen visually that both the trajectories from the simulation and real-world highly resemble to each other. By slightly tweaking the parameters, one can generate different test scenario.

As a result of a non-trivial mixing matrix, neutrinos cannot be simultaneously in a flavor and mass eigenstate. We formulate and discuss information entropic relations that quantify the associated quantum uncertainty. We also formulate a protocol to determine the Pontecorvo-Maki-Nakagawa-Sakata (PMNS) matrix from quantum manipulations and measurements on an entangled lepton-neutrino pair. The entangled state features neutrino oscillations in a conditional probability involving measurements on the lepton and the neutrino. They can be switched off by choosing a specific observable on the lepton side which is determined by the PMNS matrix. The parameters of the latter, including the CP-violating phase $\delta$, can be obtained by guessing them and improving the guess by minimizing the remaining oscillations., Comment: 16 pages, 2 figures

Microphysiometry has proved to be a useful tool for monitoring the energy metabolism of living cells and their interactions with other cells. The technique has mainly been used for monitoring two-dimensional (2D) monolayers of cells. Recently, our group showed that it is also possible to monitor the extracellular acidification rate and transepithelial electrical resistance (TEER) of 3D skin constructs in an automated assay maintaining an air–liquid interface (ALI) with a BioChip extended by 3D-printed encapsulation. In this work, we present an optimized multichannel intestine-on-a-chip for monitoring the TEER of the commercially available 3D small intestinal tissue model (EpiIntestinalTM from MatTek). Experiments are performed for 1 day, during which a 60 min cycle is repeated periodically. Each cycle consists of three parts: (1) maintain ALI; (2) application of the measurement medium or test substance; and (3) the rinse cycle. A cytotoxic and barrier-disrupting benchmark chemical (0.2% sodium dodecyl sulfate) was applied after 8 h of initial equilibration. This caused time-dependent reduction of the TEER, which could not be observed with typical cytotoxicity measurement methods. This work represents a proof-of-principle of multichannel time-resolved TEER monitoring of a 3D intestine model using an automated ALI. Reconstructed human tissue combined with the Intelligent Mobile Lab for In vitro Diagnostic technology represents a promising research tool for use in toxicology, cellular metabolism studies, and drug absorption research.

The gastrointestinal tract (GIT), in particular, the small intestine, plays a significant role in food digestion, fluid and electrolyte transport, drug absorption and metabolism, and nutrient uptake. As the longest portion of the GIT, the small intestine also plays a vital role in protecting the host against pathogenic or opportunistic microbial invasion. However, establishing polarized intestinal tissue models in vitro that reflect the architecture and physiology of the gut has been a challenge for decades and the lack of translational models that predict human responses has impeded research in the drug absorption, metabolism, and drug-induced gastrointestinal toxicity space. Often, animals fail to recapitulate human physiology and do not predict human outcomes. Also, certain human pathogens are species specific and do not infect other hosts. Concerns such as variability of results, a low throughput format, and ethical considerations further complicate the use of animals for predicting the safety and efficacy xenobiotics in humans. These limitations necessitate the development of in vitro 3D human intestinal tissue models that recapitulate in vivo-like microenvironment and provide more physiologically relevant cellular responses so that they can better predict the safety and efficacy of pharmaceuticals and toxicants. Over the past decade, much progress has been made in the development of in vitro intestinal models (organoids and 3D-organotypic tissues) using either inducible pluripotent or adult stem cells. Among the models, the MatTek's intestinal tissue model (EpiIntestinal™ Ashland, MA) has been used extensively by the pharmaceutical industry to study drug permeation, metabolism, drug-induced GI toxicity, pathogen infections, inflammation, wound healing, and as a predictive model for a clinical adverse outcome (diarrhea) to pharmaceutical drugs. In this paper, our review will focus on the potential of in vitro small intestinal tissues as preclinical research tool and as alternative to the use of animals.

Background: Existing analyses of nonpharmaceutical interventions (NPIs) against COVID19 transmission have focussed on the joint effectiveness of large-scale NPIs. With increasing data, we can move beyond estimating aggregate effects, to understanding the effects of individual interventions. In addition to effectiveness, policy decisions ought to reflect the burden different NPIs put on the population. Methods: To our knowledge, this is the largest data-driven study of NPI effectiveness to date. We collected chronological data on 9 NPIs in 41 countries between January and April 2020, using extensive fact-checking to ensure high data quality. We infer NPI effectiveness with a novel semi-mechanistic Bayesian hierarchical model, modelling both confirmed cases and deaths to increase the signal from which NPI effects can be inferred. Finally, we study the burden imposed by different NPIs with an online survey of preferences using the MaxDiff method. Results: Six NPIs had a >97.5% posterior probability of being effective: closing schools (mean reduction in R: 58%; 95% credible interval: 50% - 64%), limiting gatherings to 10 people or less (24%; 6% - 39%), closing nonessential businesses (23%; 5% - 38%), closing high-risk businesses (19%; 1% - 34%), testing patients with respiratory symptoms (18%; 8% - 26%), and stay-at-home orders (17%; 5% - 28%). These results show low sensitivity to 12 forms of varying the model and the data. The model makes sensible forecasts for countries and periods not seen during training. We combine the effectiveness and preference results to estimate effectiveness-to-burden ratios. Conclusions: Our results suggest a surprisingly large role for schools in COVID-19 transmission, a contribution to the ongoing debate about the relevance of asymptomatic carriers in disease spreading. We identify additional interventions with good effectiveness-burden tradeoffs, namely symptomatic testing, closing high-risk businesses, and limiting gathering size. Closing most nonessential businesses and issuing stay-at-home orders impose a high burden while having a limited additional effect.