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Large-scale distillation is a challenge in many respects. Particularly difficult is the purification by distillation of a compound with limited thermal stability. This article describes various aspects of these difficulties with some possible solutions. Special emphasis is placed on the collaboration of different disciplines to find pragmatic solutions to these challenges. The purification of diketene in quantities of several 1000 ta–1 is an excellent example to illustrate the different requirements. Although the distillation of diketene has been carried out by several companies for many years, there are still some aspects that deserve special attention.

Background: The complexity of research informed consent forms makes it hard for potential study participants to make informed consent decisions. In response, new rules for human research protection require informed consent forms to begin with a key information section that potential study participants can read and understand. This research study builds on exiting guidance on how to write research key information using plain language. Objective: The aim of this study was to develop a valid and reliable tool to evaluate and improve the readability, understandability, and actionability of the key information section on research informed consent forms. Methods: We developed an initial list of measures to include on the tool through literature review; established face and content validity of measures with expert input; conducted four rounds of reliability testing with four groups of reviewers; and established construct validity with potential research participants. Key Results: We identified 87 candidate measures via literature review. After expert review, we included 23 items on the initial tool. Twenty-four raters conducted 4 rounds of reliability testing on 10 informed consent forms. After each round, we revised or eliminated items to improve agreement. In the final round of testing, 18 items demonstrated substantial inter-rater agreement per Fleiss' Kappa (average = .73) and Gwet's AC1 (average = .77). Intra-rater agreement was substantial per Cohen's Kappa (average = .74) and almost perfect per Gwet's AC1 (average = 0.84). Focus group feedback (N = 16) provided evidence suggesting key information was easy to read when rated as such by the Readability, Understandability and Actionability of Key Information (RUAKI) Indicator. Conclusion: The RUAKI Indicator is an 18-item tool with evidence of validity and reliability investigators can use to write the key information section on their informed consent forms that potential study participants can read, understand, and act on to make informed decisions. [HLRP: Health Literacy Research and Practice. 2024;8(1):e29–e37.]

Antiferroelectrics are important in emerging energy-storage technologies. Here, the authors present an approach to adjust their local structure and defect chemistry, in order to overcome the current limitations and make them suitable for environmentally-friendly dielectric energy storage.

Abstract Interface stability is a key factor for stable operation of electronic and electrochemical devices. This contribution introduces an approach for the operando analysis of interfaces using photoelectron spectroscopy employing a solid oxide electrochemical cell. The combined chemical and electronic information provided by the experiment reveals that not only chemical but also electrostatic boundary conditions are essential for interface stability. The approach is demonstrated using (anti‐)ferroelectric (Pb,La)(Zr,Sn,Ti)O3 dielectrics.

It has been recently reported that n-type single crystalline SnS exhibits a large band bending (∼1 eV) at the interface with MoO3, which is a large work function material. In this study, we applied this interface to solar cells for the first time and evaluated its photovoltaic properties. The highest VOC achieved was 437 mV. Although this value is the highest ever recorded for SnS solar cells, it was lower than the expected value of 700–800 mV. The highest power conversion efficiency (PCE) was 4.4%. Based on an analysis of the device parameters, we propose methods for improving the device performance, including VOC, the short-circuit current, and PCE. The carrier-collection length of the n-type SnS single crystals was estimated to be ∼200 nm based on the external quantum efficiency measurements. Therefore, this study demonstrates that the VOC of SnS solar cells can be improved by fabricating a junction with MoO3 thin films.

1897 veröffentlichte der Abel’sche Kunstverlag in Christiania (Oslo) das Kartenalbum Fra Finmarken mit Darstellungen und Texten, die vom Leben und der Natur in Nordnorwegen inspiriert sind. Während die Bilder von Agnes Thorsen (1862–1955), Gründerin, Schulleiterin und Lehrerin an der privaten Mittelschule Nordstrand, angefertigt wurden, sind die Textfragmente Zitate zeitgenössischer Autoren. Fra Finmarken ist Thorsens einzige eigenständige Publikation. Mein Artikel widmet sich dem Hintergrund und der Rezeptionsgeschichte sowie dem gesellschaftlichen und kunsthistorischen Kontext ihres Werks. Ich diskutiere, wie Nordnorwegen im Album dargestellt ist, und zeige, wie Thorsens Bilder in einen Dialog mit den zitierten Texten treten.

Abstract Background One key approach for anticancer therapy is drug combination. Drug combinations can help reduce doses and thereby decrease side effects. Furthermore, the likelihood of drug resistance is reduced. Distinct alterations in tumor metabolism have been described in past decades, but metabolism has yet to be targeted in clinical cancer therapy. Recently, we found evidence for synergism between dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor, and the HIF-1α inhibitor PX-478. In this study, we aimed to analyse this synergism in cell lines of different cancer types and to identify the underlying biochemical mechanisms. Methods The dose-dependent antiproliferative effects of the single drugs and their combination were assessed using SRB assays. FACS, Western blot and HPLC analyses were performed to investigate changes in reactive oxygen species levels, apoptosis and the cell cycle. Additionally, real-time metabolic analyses (Seahorse) were performed with DCA-treated MCF-7 cells. Results The combination of DCA and PX-478 produced synergistic effects in all eight cancer cell lines tested, including colorectal, lung, breast, cervical, liver and brain cancer. Reactive oxygen species generation and apoptosis played important roles in this synergism. Furthermore, cell proliferation was inhibited by the combination treatment. Conclusions Here, we found that these tumor metabolism-targeting compounds exhibited a potent synergism across all tested cancer cell lines. Thus, we highly recommend the combination of these two compounds for progression to in vivo translational and clinical trials.

Multilayered doped BaTiO3 thin films have been fabricated by physical vapor deposition (PVD) on low-cost polycrystalline substrates with the aim to improve dielectric properties by controlling point charge defects at the interfaces. We show that carefully designed interfaces lead to increasing the relative permittivity of the BaTiO3 thin films, in contradiction with the common belief that interfaces behave as dead layers. High relative permittivity up to 1030 and tanδ = 4% at 100 kHz and room temperature were obtained on BaTiO3 multilayered films deposited on Si/Pt substrates by PVD. The large permittivity is suspected to be an extrinsic contribution due to band bending at the interfaces, as inferred by in-situ X-ray photoelectron spectroscopy. A 20-nm depletion layer was found to be associated with an interdiffusion of dopants, as measured by depth profiling with time-of-flight secondary ion mass spectrometry. The films exhibit high permittivity and low dielectric losses stable between 200 and 400 K, which meet the requirement of electronic applications.

Abstract Background Despite an improvement of prognosis in breast and colon cancer, the outcome of the metastatic disease is still severe. Microevolution of cancer cells often leads to drug resistance and tumor-recurrence. To target the driving forces of the tumor microevolution, we focused on synergistic drug combinations of selected compounds. The aim is to prevent the tumor from evolving in order to stabilize disease remission. To identify synergisms in a high number of compounds, we propose here a three-step concept that is cost efficient, independent of high-throughput machines and reliable in its predictions. Methods We created dose response curves using MTT- and SRB-assays with 14 different compounds in MCF-7, HT-29 and MDA-MB-231 cells. In order to efficiently screen for synergies, we developed a screening tool in which 14 drugs were combined (91 combinations) in MCF-7 and HT-29 using EC25 or less. The most promising combinations were verified by the method of Chou and Talalay. Results All 14 compounds exhibit antitumor effects on each of the three cell lines. The screening tool resulted in 19 potential synergisms detected in HT-29 (20.9%) and 27 in MCF-7 (29.7%). Seven of the top combinations were further verified over the whole dose response curve, and for five combinations a significant synergy could be confirmed. The combination Nutlin-3 (inhibition of MDM2) and PX-478 (inhibition of HIF-1α) could be confirmed for all three cell lines. The same accounts for the combination of Dichloroacetate (PDH activation) and NHI-2 (LDH-A inhibition). Our screening method proved to be an efficient tool that is reliable in its projections. Conclusions The presented three-step concept proved to be cost- and time-efficient with respect to the resulting data. The newly found combinations show promising results in MCF-7, HT-29 and MDA-MB231 cancer cells.

Abstract Background Tumorigenesis is a multi-step process which is accompanied by substantial changes in genome organization. The development of these changes is not only a random process, but rather comprise specific DNA regions that are prone to the reorganization process. Results We have analyzed previously published SNP arrays from three different cancer types (pancreatic adenocarcinoma, breast cancer and metastatic melanoma) and from non-malignant control samples. We calculated segmental copy number variations as well as breakpoint regions. Some of these regions were not randomly involved in genome reorganization since we detected fifteen of them in at least 20% of all tumor samples and one region on chromosome 9 where 43% of tumors have a breakpoint. Further, the top-15 breakpoint regions show an association to known fragile sites. The relevance of these common breakpoint regions was further confirmed by analyzing SNP arrays from 917 cancer cell lines. Conclusion Our analyses suggest that genome reorganization is common in tumorigenesis and that some breakpoint regions can be found across all cancer types, while others exclusively occur in specific entities.

The Electroceramics XVII conference, held August 24–28, 2020, was the first fully online conference in the biannual Electroceramics conference series. This communication provides a summary of the experiences gathered during the organization and execution of the meeting. Besides discussing the various pros and cons, we also aim to provide basic guidelines for scientific online conferencing, which will hopefully encourage individual readers to consider virtual meetings as an alternative or a supplement to in-person events, even after the COVID-19 pandemic.

Central nervous system (CNS) involvement in Burkitt lymphoma (BL) poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We described prognostic significance of CNS involvement and incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathologic data on adults with BL diagnosed between 2009 and 2018 across 30 US institutions. We examined associations between baseline CNS involvement, patient characteristics, complete response (CR) rates, and survival. We also examined risk factors for CNS recurrence. Nineteen percent (120/641) of patients (age 18-88 years) had CNS involvement. It was independently associated with HIV infection, poor performance status, involvement of ≥2 extranodal sites, or bone marrow involvement. First-line regimen selection was unaffected by CNS involvement (P=0.93). Patients with CNS disease had significantly lower rates of CR (59% versus 77% without; P

Abstract Background: A feedforward pathological signaling loop generated by TNFα and IFN-γ synergy in the inflamed lung, driving CXCL-10 (IP-10) and CXCL-9 chemokine-mediated activated T-cell and monocyte/macrophage tissue recruitment, may define the inflammatory biology of lethal COVID-19 respiratory failure. Methods: To assess TNFα-antagonist therapy, 18 hospitalized adults with hypoxic respiratory failure and COVID-19 pneumonia received single-dose infliximab-abda therapy 5 mg/kg intravenously between April and December 2020. The primary endpoint was time to increase in oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) by ≥50 compared to baseline and sustained for 48 h. Secondary endpoints included 28-day mortality, dynamic cytokine profiles, secondary infections, duration of supplemental oxygen support, and hospitalization. Findings: Patients were predominantly in critical respiratory failure (15/18, 83%), male (14/18, 78%), above 60 years (median 63 years, range 31–80), race-ethnic minorities (13/18, 72%), lymphopenic (13/18, 72%), steroid-treated (17/18, 94%), with a median ferritin of 1953 ng/ml. Sixteen patients (89%) met the primary endpoint within a median of 4 days; 14/18 (78%) were discharged in a median of 8 days and were alive at 28-day follow-up. Three deaths were attributed to secondary lung infection. Mean plasma IP-10 levels declined sharply from 9183 to 483 pg/ml at Day 3 and 146 pg/ml at Day 14/discharge. Significant Day 3 declines in IFN- $\gamma $ , TNFα, IL-27, CRP, and ferritin occurred. IP-10 and CXCL-9 declines were strongly correlated among patients with lymphopenia reversal (Day 3, Pearson r: 0.98, P-value 0.0006). Interpretation: Infliximab-abda may rapidly abrogate pathological inflammatory signaling to facilitate clinical recovery in severe and critical COVID-19.

Mutation of the isocitrate-dehydrogenase (IDH) enzymes is one of the central research topics regarding gliomagenesis. Indeed, 70% of gliomas are associated with a gain-of-function IDH mutation and consequently synthesize the oncometabolite, 2-hydroxyglutarate (2-HG). This review aims to elucidate the effects of 2-HG on gliomagenesis. 2-HG promotes tumorigenesis by impacting metabolism, vascularization and altering the epigenome of glioma cells. Glioma metabolism and vascularization is altered by 2-HG’s effect on the stability of hypoxia-inducible factor (HIF) and inhibition of endostatin. However, 2-HG’s impacts on epigenetic mechanisms are more profound to gliomagenesis. Through competitive inhibition of JHDMs and TET proteins, 2-HG orchestrates histone and DNA hypermethylation, which is associated with gene silencing and dedifferentiation of cells. The hypermethylator phenotype induced by 2-HG also results in alterations of the interaction of the immune system with the tumour. Additionally, this study reviews 2-HG promotion of tumorigenesis by inhibiting repair of DNA alkylation damage through competitive inhibition of AlkB proteins.

Hematite has been proposed as a suitable photocatalyst for water splitting based on its stability and appealing optical band gap, but its performance has not reached theoretical expectations. Here the authors show that this is due to intra-gap polaronic states that reduce the effective electronic band gap.

It is commonly agreed that the plural -s has become a part of Standard German inflection, yet in dialects such as Alemannic it is often seen as an intruder. We challenge this view based on data from a written survey amongst speakers of Swiss German dialects. Our analysis of pluralised loanwords (e. g. Mango) and abbreviations (e. g. WG ‘flat share’) shows a strong effect of both speakers’ age and grammatical gender that points towards a progressive integration of the plural -s into the dialectal system. While masculine and neuter nouns can express number syntagmatically (using articles that differ in singular and plural), feminine nouns rely heavily on suffixes (as the definite article is d’ in both cases). A comparison of the -s plural with traditional dialectal plurals shows clear advantages for -s plurals in both cue strength (output) and scope (input) of the plural schema. We argue that it is due to this that feminine nouns show a significantly higher percentage of -s plurals compared with masculine and neuter nouns in speakers aged 25 and above. The difference disappears for younger speakers while the overall number of -s plurals increases drastically. Combined, we have an apparent time scenario that shows how the -s plural is first borrowed with nouns that rely on overt plural markers, and later spreads to most loans and other words with non-native structure.