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The recently discovered ferroelectric nematic liquids incorporate to the functional combination of fluidity, processability and anisotropic optical properties of nematic liquids, an astonishing range of physical properties derived from the phase polarity. Among them, the remarkably large values of second order optical susceptibility encourage to exploit these new materials for non-linear photonic applications. Here we show that photopatterning of the alignment layer can be used to structure polarization patterns. To do so, we take advantage of the flexoelectric effect and design splay structures that geometrically define the polarization direction. We demonstrate the creation of periodic polarization structures and the possibility of guiding polarization by embedding splay structures in uniform backgrounds. The demonstrated capabilities of polarization patterning, open a promising new route for the design of ferroelectric nematic based photonic structures and their exploitation. Ferroelectric Nematic Liquid Crystals (FNLCs) have potential in applications due to their unique combination of fluidity, spontaneous polarization, large dielectric permittivity, and second-order non-linear optical properties. Sebastian et al. show the patterning of electric polarization in FNLCs by photoalignment which exploit flexoelectric coupling between polarization and splay director deformations.

An actinobacterial strain A23T, isolated from adult ant Camponotus vagus collected in Ryazan region (Russia) and established as tetracenomycin X producer, was subjected to a polyphasic taxonomic study. Morphological characteristics of this strain included well-branched substrate mycelium and aerial hyphae fragmented into rod-shaped elements. Phylogenetic analyses based on 16S rRNA gene and genome sequences showed that strain A23T was most closely related to Amycolatopsis pretoriensis DSM 44654T. Average nucleotide identity and digital DNA–DNA hybridization values between the genome sequences of isolate A23T and its closest relative, Amycolatopsis pretoriensis DSM 44654T, were 39.5% and 88.6%, which were below the 70% and 95–96% cut-off point recommended for bacterial species demarcation, respectively. The genome size of the isolate A23T was 10,560,374 bp with a DNA G + C content of 71.2%. The whole-cell hydrolysate contained meso-diaminopimelic acid and arabinose and galactose as main diagnostic sugars as well as ribose and rhamnose. It contained MK-9(H4) as the predominant menaquinone and iso-C16:0, iso-C15:0, anteiso-C17:0 and C16:0 as the major cellular fatty acids. Diphosphatidylglycerol and phosphatidylethanolamine prevailed among phospholipids. Mycolic acids were not detected. Based on the phenotypic, genomic and phylogenetic data, isolate A23T represents a novel species of the genus Amycolatopsis, for which the name Amycolatopsis camponoti sp. nov. is proposed, and the type strain is A23T (= DSM 111725T = VKM 2882T).

Background The Borna disease virus (BoDV-1) is an emerging zoonotic virus causing severe and mostly fatal encephalitis in humans. Methods and Results A local cluster of fatal BoDV-1 encephalitis cases was detected in the same village three years apart affecting two children. While the first case was diagnosed late in the course of disease, a very early diagnosis and treatment attempt facilitated by heightened awareness was achieved in the second case. Therapy started as early as day 12 of disease. Antiviral therapy encompassed favipiravir and ribavirin, and, after bioinformatic modelling, also remdesivir. As the disease is immunopathogenetically mediated, an intensified anti-inflammatory therapy was administered. Following initial impressive clinical improvement, the course was also fatal, although clearly prolonged. Viral RNA was detected by qPCR in tear fluid and saliva, constituting a possible transmission risk for health care professionals. Highest viral loads were found post mortem in the olfactory nerve and the limbic system, possibly reflecting the portal of entry for BoDV-1. Whole exome sequencing in both patients yielded no hint for underlying immunodeficiency. Full virus genomes belonging to the same cluster were obtained in both cases by next-generation sequencing. Sequences were not identical, indicating viral diversity in natural reservoirs. Specific transmission events or a common source of infection were not found by structured interviews. Patients lived 750m apart from each other and on the fringe of the settlement, a recently shown relevant risk factor. Conclusion Our report highlights the urgent necessity of effective treatment strategies, heightened awareness and early diagnosis. Gaps of knowledge regarding risk factors, transmission events, and tailored prevention methods become apparent. Whether this case cluster reflects endemicity or a geographical hot spot needs further investigation.

Late-onset Fuchs endothelial corneal dystrophy (FECD) is a disease affecting the corneal endothelium (CE), associated with a cytosine-thymine-guanine repeat expansion at the CTG18.1 locus in the transcription factor 4 (TCF4) gene. It is unknown whether CTG18.1 expansions affect global methylation including TCF4 gene in CE or whether global CE methylation changes at advanced age. Using genome-wide DNA methylation array, we investigated methylation in CE from FECD patients with CTG18.1 expansions and studied the methylation in healthy CE at different ages. The most revealing DNA methylation findings were analyzed by gene expression and protein analysis. 3488 CpGs had significantly altered methylation pattern in FECD though no substantial changes were found in TCF4. The most hypermethylated site was in a predicted promoter of aquaporin 1 (AQP1) gene, and the most hypomethylated site was in a predicted promoter of coagulation factor V (F5 for gene, FV for protein). In FECD, AQP1 mRNA expression was variable, while F5 gene expression showed a ~ 23-fold increase. FV protein was present in both healthy and affected CE. Further gene expression analysis of coagulation factors interacting with FV revealed a ~ 34-fold increase of thrombomodulin (THBD). THBD protein was detected only in CE from FECD patients. Additionally, we observed an age-dependent hypomethylation in elderly healthy CE.Thus, tissue-specific genome-wide and gene-specific methylation changes associated with altered gene expression were discovered in FECD. TCF4 pathological methylation in FECD because of CTG18.1 expansion was ruled out.

The increase in multi-drug resistant pathogenic bacteria is making our current arsenal of clinically used antibiotics obsolete, highlighting the urgent need for new lead compounds with distinct target binding sites to avoid cross-resistance. Here we report that the aromatic polyketide antibiotic tetracenomycin (TcmX) is a potent inhibitor of protein synthesis, and does not induce DNA damage as previously thought. Despite the structural similarity to the well-known translation inhibitor tetracycline, we show that TcmX does not interact with the small ribosomal subunit, but rather binds to the large subunit, within the polypeptide exit tunnel. This previously unappreciated binding site is located adjacent to the macrolide-binding site, where TcmX stacks on the noncanonical basepair formed by U1782 and U2586 of the 23S ribosomal RNA. Although the binding site is distinct from the macrolide antibiotics, our results indicate that like macrolides, TcmX allows translation of short oligopeptides before further translation is blocked.

Purpose To determine risk factors for coronavirus disease 2019 (COVID-19) in healthcare workers (HCWs), characterize symptoms, and evaluate preventive measures against SARS-CoV-2 spread in hospitals. Methods In a cross-sectional study conducted between May 27 and August 12, 2020, after the first wave of the COVID-19 pandemic, we obtained serological, epidemiological, occupational as well as COVID-19-related data at a quaternary care, multicenter hospital in Munich, Germany. Results 7554 HCWs participated, 2.2% of whom tested positive for anti-SARS-CoV-2 antibodies. Multivariate analysis revealed increased COVID-19 risk for nurses (3.1% seropositivity, 95% CI 2.5–3.9%, p = 0.012), staff working on COVID-19 units (4.6% seropositivity, 95% CI 3.2–6.5%, p = 0.032), males (2.4% seropositivity, 95% CI 1.8–3.2%, p = 0.019), and HCWs reporting high-risk exposures to infected patients (5.5% seropositivity, 95% CI 4.0–7.5%, p = 0.0022) or outside of work (12.0% seropositivity, 95% CI 8.0–17.4%, p p = 0.00018) and the symptom taste disorder was strongly associated with COVID-19 (29.8% seropositivity, 95% CI 24.3–35.8%, p Conclusion Awareness of the identified COVID-19 risk factors and successful surveillance strategies are key to protecting HCWs against SARS-CoV-2, especially in settings with limited vaccination capacities or reduced vaccine efficacy.

Mixed flowing gas (MFG) testing is used to demonstrate the ability of an electronic product or system to survive in a corrosive environment. MFG testing is designed to corrode copper and silver, which are often used as electrical conductors in electronic products. However, MFG tests have failed to identify issues in recent years. These failures have been predominately related to the corrosion of silver. To understand these test escapes, the corrosion of silver and copper corrosion under MFG is examined. For comparison, a flower of sulfur (FoS) test at 75°C was also conducted. The test results show that the rate of copper and silver corrosion is not equivalent but varies depending on the gas concentration, which explains the failure escapes.

New derivatives of 3,5-dibenzoylspiropiperidinium salts were obtained by the previously developed method of cyclization of Mannich methylidene monobases of arylaliphatic 1,5-diketones and their antibacterial activity was studied. The structure of one of the salts was determined by X-ray structural analysis. The study of the mechanism of action using the pDualrep2 reporter system showed that some compounds cause the SOS response in the bacterial cell.

Regular convolutions of arithmetical functions were first defined by Narkiewicz (Colloq Math 10:81–94, 1963). Useful identities regarding generalizations of the totient-counting function and Ramanujan sums were later proven for regular convolutions by McCarthy (Port Math 27(1):1–13, 1968) and Rao (Studies in arithmetical functions, PhD thesis, 1967). We introduce semi-regular convolutions as a generalization of the regular convolutions and show that many of these identities still hold. In particular, special cases of the generalized Ramanujan sums correspond to the corresponding expected generalizations of the totient-counting and Mobius functions. Then we demonstrate that the class of semi-regular convolutions is the broadest generalization to multiplicative-preserving convolutions possible in which even the most basic of these identities still hold. Finally, we introduce a convolution related to Cohen’s infinitary convolution (Int J Math Math Sci 16(2):373–383, 1993) that is semi-regular. This convolution has never been studied to the best of the authors’ knowledge and possesses a property that distinguishes it from all of the other semi-regular convolutions.

Amplification of the MYCN oncogene occurs in approximately 25% of primary neuroblastomas and is the single most powerful biological marker of poor prognosis in this disease. MYCN transcriptionally regulates a range of biological processes important for cancer, including cell metabolism. The MYCN-regulated metabolic gene SLC16A1, encoding the lactate transporter monocarboxylate transporter 1 (MCT1), is a potential therapeutic target. Treatment of neuroblastoma cells with the MCT1 inhibitor SR13800 increased intracellular lactate levels, disrupted the nicotinamide adenine dinucleotide (NADH/NAD(+)) ratio and decreased intracellular glutathione levels. Metabolite tracing with 13C-glucose and 13C-glutamine following MCT1 inhibitor treatment revealed increased quantities of tricarboxylic acid (TCA) cycle intermediates and increased oxygen consumption rate. MCT1 inhibition was highly synergistic with vincristine under cell culture conditions, but this combination was ineffective against neuroblastoma xenografts in mice. Post-treatment xenograft tumors had increased expression of the MCT1 homolog MCT4/SLC16A, a known resistance factor to MCT1 inhibition. We found that MCT4 was negatively regulated by MYCN in luciferase reporter assays and its expression in neuroblastoma cells was increased under hypoxic conditions and following hypoxia-inducible factor (HIF1) induction, suggesting that MCT4 may contribute to resistance to MCT1 inhibitor treatment in hypoxic neuroblastoma tumors. Co-treatment of neuroblastoma cells with inhibitors of MCT1 and LDHA, the enzyme responsible for lactate production, resulted in a large increase in intracellular pyruvate and was highly synergistic in decreasing neuroblastoma cell viability. These results highlight the potential of targeting MCT1 in neuroblastoma in conjunction with strategies that involve disruption of pyruvate homeostasis and indicate possible resistance mechanisms.

Miner’s rule assumes that damage in solder interconnects accumulates linearly under cyclic loading and is independent of the load sequence. Under these constraints, damage is equivalent to cycle ratio, defined as the ratio of the applied cycles to the cycles to failure for the specific cyclic loading condition. Due to these inherent assumptions, Miner’s rule can inaccurately estimate solder interconnect life under sequential loading conditions. A nonlinear damage model with load-dependent damage exponents would take into account the effect of loading sequence under sequential loading conditions. In the nonlinear damage model, damage is related to cycle ratio using a power law relationship with a load-dependent damage exponent. This paper presents an experimental approach to determine the load-dependent exponents under three load levels. Load drop in the specimens, as a result of cyclic loading induced changes, is used as the criterion for the damage state. The tests consisted of a series of constant amplitude (standalone) and blocks of sequential variable amplitude cyclic shear tests in a thermo-mechanical micro-scale analyzer. The load-dependent damage exponents were developed for SAC305 (96.5%Sn + 3.0%Ag + 0.5Cu) solder. The result of the study can be used for SAC305 damage accumulation model formulation. Further, the experimental approach can be used to generate additional fatigue data under variable amplitude loads.

The present report describes our efforts to identify new structural classes of compounds having promising antibacterial activity using previously published double-reporter system pDualrep2. This semi-automated high-throughput screening (HTS) platform has been applied to perform a large-scale screen of a diverse small-molecule compound library. We have selected a set of more than 125,000 molecules and evaluated them for their antibacterial activity. On the basis of HTS results, eight compounds containing 2-pyrazol-1-yl-thiazole scaffold exhibited moderate-to-high activity against ΔTolC Escherichia coli. Minimum inhibitory concentration (MIC) values for these molecules were in the range of 0.037–8 μg ml−1. The most active compound 8 demonstrated high antibacterial potency (MIC = 0.037 μg ml−1), that significantly exceed that measured for erythromycin (MIC = 2.5 μg ml−1) and was comparable with the activity of levofloxacin (MIC = 0.016 μg ml−1). Unfortunately, this compound showed only moderate selectivity toward HEK293 eukaryotic cell line. On the contrary, compound 7 was less potent (MIC = 0.8 μg ml−1) but displayed only slight cytotoxicity. Thus, 2-pyrazol-1-yl-thiazoles can be considered as a valuable starting point for subsequent optimization and morphing.

Background Identification of biomarkers associated with benefit of adjuvant chemotherapy in stage II/III colon cancer is an important task. Methods Vessel density (VD) and tumour stroma were analysed in a randomised-trial-derived discovery cohort (n = 312) and in a stage II/III group of a population-based validation cohort (n = 85). VD was scored separately in the tumour centre, invasive margin and peritumoral stroma compartments and quantitated as VD/total analysed tissue area or VD/stroma area. Results High stroma-normalised VD in the invasive margin was associated with significantly longer time to recurrence and overall survival (OS) (p = 0.002 and p = 0.006, respectively) in adjuvant-treated patients of the discovery cohort, but not in surgery-only patients. Stroma-normalised VD in the invasive margin and treatment effect were significantly associated according to a formal interaction test (p = 0.009). Similarly, in the validation cohort, high stroma-normalised VD was associated with OS in adjuvant-treated patients, although statistical significance was not reached (p = 0.051). Conclusion Through the use of novel digitally scored vessel-density-related metrics, this exploratory study identifies stroma-normalised VD in the invasive margin as a candidate marker for benefit of adjuvant 5-FU-based chemotherapy in stage II/III colon cancer. The findings, indicating particular importance of vessels in the invasive margin, also suggest biological mechanisms for further exploration.

High-throughput screening identified a new class of antibacterial compounds based on N-pyridyl-substituted p- and m-carboxypiperidine amides. Constructs with the two reporter genes RFP and Katushka2S allowed the detection of compounds that inhibit protein translation against DNA biosynthesis. Some agents of this class demonstrated antibacterial activity by inhibiting translation. The most promising compound had an MIC of 12 μg/mL. Thus, this class could become a valuable platform for developing new compounds with higher antibacterial activity and selectivity.