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We present the motivation, experience, and learnings from a data challenge conducted at a large pharmaceutical corporation on the topic of subgroup identification. The data challenge aimed at exploring approaches to subgroup identification for future clinical trials. To mimic a realistic setting, participants had access to 4 Phase III clinical trials to derive a subgroup and predict its treatment effect on a future study not accessible to challenge participants. A total of 30 teams registered for the challenge with around 100 participants, primarily from Biostatistics organization. We outline the motivation for running the challenge, the challenge rules, and logistics. Finally, we present the results of the challenge, the participant feedback as well as the learnings. We also present our view on the implications of the results on exploratory analyses related to treatment effect heterogeneity. [ABSTRACT FROM AUTHOR]

Objectives: Midostaurin is an oral multitargeted tyrosine kinase inhibitor for the treatment of acute myeloid leukemia (AML). Therapeutic drug monitoring of midostaurin may support its safe use when suspecting toxicity or combined with strong CYP3A4 inhibitors. Methods: A stable isotope dilution liquid chromatography–tandem mass spectrometry method was developed and validated for the determination and quantification of midostaurin in human plasma and serum. Midostaurin serum concentrations were analyzed in 12 patients with FMS‐like tyrosine kinase 3 (FLT3)‐mutated AML during induction chemotherapy with cytarabine, daunorubicin, and midostaurin. Posaconazole was used as prophylaxis of invasive fungal infections. Results: Linear quantification of midostaurin was demonstrated across a concentration range of 0.01–8.00 mg/L. Inter‐ and intraday imprecisions of the proposed method were well within ±10%. Venous blood samples were taken in nine and three patients in the first and second cycle of induction chemotherapy. Median (range) midostaurin serum concentration was 7.9 mg/L (1.5–26.1 mg/L) as determined in 37 independent serum specimens. Conclusion: In a real‐life cohort of AML patients, interindividual variability in midostaurin serum concentrations was high, highlighting issues concerning optimal drug dosing in AML patients. A personalized dosage approach may maximize the safety of midostaurin. Prospective studies and standardization of analytical methods to support such an approach are needed. [ABSTRACT FROM AUTHOR]

Radical trifluoromethoxylation is an attractive approach to prepare compounds featuring the important OCF3 group, however most existing methods have focused on aromatic substrates. Here, we report novel methodologies with alkenyl substrates employing bis(trifluoromethyl)peroxide (BTMP) as a practical and comparatively atom economical trifluoromethoxylating reagent. With silyl enol ether substrates, switching reaction solvent allows for the synthesis of either α‐(trifluoromethoxy)ketone products or unprecedented alkenyl‐OCF3 species. Furthermore, allyl silanes have been employed as substrates for the first time, affording allyl(trifluoromethyl)ether products in good yields. In each case, the methods operate at room temperature without large excesses of the alkene substrate while, in contrast to previous radical trifluoromethoxylation reactions, no catalyst, light or other activators are required. [ABSTRACT FROM AUTHOR]

The preparation and structural characterization of [NEt3Me]2[SCl6] is described, which is the first example of a [SCl6]2− dianion and of a halosulfate anion of the type [SxXy]z− in general. This dianion belongs to the group of 14‐valence electron AB6E systems and forms an octahedral structure in the solid‐state. Interestingly, co‐crystallization with CH2Cl2 affords [NEt3Me]2[SCl6]⋅4 CH2Cl2 containing [SCl6]2− dianions with C4v symmetry. As suggested by quantum‐chemical calculations, the distortion of the structure is not caused by a stereochemically active lone pair but by enhanced hydrogen bonding interactions with CH2Cl2. At elevated temperatures, [NEt3Me]2[SCl6] decomposes to various sulfur chlorine compounds as shown by Raman spectroscopy. Cooling back to room temperature results in the selective formation of [NEt3Me]2[SCl6] which is comparable to the well‐studied SCl4. [ABSTRACT FROM AUTHOR]

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BACKGROUND There is increasing consumer demand for olive oil to be traceable. However, genotype, environmental factors, and stage of maturity, all affect the flavor and composition of both the olives and olive oil. Few studies have included all three variables. Key metabolites include lipids, phenolics, and a wide range of volatile organic compounds (VOCs), which provide the olives and oil with their characteristic flavor. Here we aim to identify markers that are able to discriminate between cultivars, that can identify growth location, and can discriminate stages of fruit maturity. 'Nocellara messinese' and 'Carolea' olive fruits were grown at three locations differing in altitude in Calabria, Italy, and harvested at three stages of maturity. Oil was analyzed from the two most mature stages. RESULTS: Nine and 20 characters discriminated all fruit and oil samples respectively, and relative abundance of two fatty acids distinguished all oils. Whole VOC profiles discriminated among the least mature olives, and oil VOC profiles discriminated location and cultivar at both stages. Three VOCs putatively identified as hexanal, methyl acetate, and 3‐hexen‐1‐ol differentiated all samples of oils from the most mature fruit stage. CONCLUSION: The results confirm that interactions of location, cultivar and fruit maturity stage are critical for the overall pattern of aroma compounds, and identify potential markers of commercial relevance. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Aims: To describe the population pharmacokinetics (PK) and probability of target attainment (PTA) of continuous infusion (CI) of meropenem in septic patients receiving renal replacement therapy (RRT). Methods: Fifteen patients without RRT, 13 patients receiving sustained low‐efficiency dialysis and 12 patients receiving continuous veno‐venous haemodialysis were included. Population PK analysis with Monte Carlo simulations for different dosing regimens was performed. For minimum inhibitory concentration 2 mg/L was chosen. The target was set as 50% time ≥4× minimum inhibitory concentration. Results: The PK of meropenem was best described by a 1‐compartment model with linear elimination. Serum creatinine, residual diuresis and time on RRT, with no difference between sustained low‐efficiency dialysis and continuous veno‐venous haemodialysis, were found to be significant covariates affecting clearance, explaining >20% of the clearance between subject variability. PTA analysis showed that in patients with RRT, 2 g/24 h, meropenem CI achieved a PTA of 95%. In patients without RRT, the target was achieved with 3 g/24 h CI or prolonged infusion of 1 g meropenem over 8 hours but not with bolus application of 1 g meropenem for 8 hours. Only 2 patients (both without RRT) had meropenem concentrations below the target level. However, approximately half of the patients with RRT receiving CI 3 g/24 h meropenem had toxic concentrations. Conclusion: We found relevant PK variability for meropenem CI in septic patients with or without RRT, leading to a substantial risk for overdosing in patients with RRT. This finding highlights the strong demand for personalized dosing in critically ill patients. [ABSTRACT FROM AUTHOR]

Insects play crucial roles in nearly every ecosystem and provide a wide array of ecosystem services. However, both managed and wild insect populations face threats from parasites and pathogens, which require surveillance to mitigate. Current infectious disease surveillance methods for insects often involve invasive, time‐consuming and occasionally destructive techniques, such as manual inspections and molecular detection. Volatile organic compound (VOC) surveillance provides a real‐time, accurate and non‐invasive alternative for disease detection and has been well‐established in humans and livestock. Recent advances in sensor technology now allow for the development of in‐field VOC surveillance devices. This review explores the need for disease surveillance in insects and highlights recent advances of using VOCs for this purpose, focusing on honey bees as an example. We outline potential applications, challenges and future prospects of using VOCs for insect disease surveillance, providing examples of how this technology could be globally applied to mitigate the impacts of disease in a range of insect systems. [ABSTRACT FROM AUTHOR]

Peripheral neuropathy is a common side effect of paclitaxel. Clinical studies suggest that different paclitaxel formulations influence the severity and time course of paclitaxel‐induced peripheral neuropathy. We compared two paclitaxel formulations, nanoparticle albumin‐bound paclitaxel (nab‐paclitaxel) and Cremophor EL paclitaxel (CreEL‐paclitaxel), for their toxicity, distribution, and clearance in the peripheral nervous system. Neuronal F11 cells were used to detect changes in morphology, cell nuclei size, and cell viability after nab‐ or CreEL‐paclitaxel treatment via MTT Assay and immunohistochemistry. C57BL/6 mice were treated with 50 mg/kg of nab‐paclitaxel or CreEL‐paclitaxel. Paclitaxel levels in serum, liver, dorsal root ganglia (DRG), and sciatic nerve (SCN) were measured by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Accumulation of paclitaxel in DRG neurons and SCN was visualized by immunostainings. Neurotoxicity was evaluated after a 4‐week treatment regime with nab‐ or CreEL‐paclitaxel by nerve morphology, behavioral, and functional assays. In vitro cell nuclei size and morphology were similar between the two treatment groups. Viability was increased in neurons exposed to nab‐paclitaxel compared to CreEL‐paclitaxel. In vivo paclitaxel mostly accumulated in DRG. SCN displayed lower paclitaxel uptake. The two paclitaxel formulations mainly accumulated in neurofilament 200‐positive large‐caliber neurons and less in Isolectin B4‐, or calcitonin gene‐related peptide‐positive small‐caliber neurons. Sensory nerve conduction studies demonstrated increased sensory latencies after 11 days in nab‐paclitaxel treated animals, while an increase occurred after 22 days in CreEL‐paclitaxel treated animals. Behavioral testing did not reveal significant differences between the different groups. Skin denervation, axon count, myelin thickness, and F4/80‐positive cell accumulation were comparable between the two treatment groups. Our findings indicate that different drug formulations impact the severity of neuropathy induced by paclitaxel via different tissue uptake. Neurotoxicity was comparable between the two paclitaxel formulations. [ABSTRACT FROM AUTHOR]

Several 1,1′‐diphosphanyl‐substituted metallocenes of magnesium (magnesocenes) were synthesized, structurally characterized, and their reactivity and coordination chemistry were investigated. Transmetalation of these magnesocenes gives access to group 14 metallocenes (tetrelocenes), as well as to group 15 stibonocenes. These s‐ and p‐block metallocenes represent a novel class of bis(phosphanyl) ligands, exhibiting Lewis‐amphiphilic character. Their coordination chemistry towards different transition‐metal and main‐group fragments was investigated and different complexes are presented. [ABSTRACT FROM AUTHOR]

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Money spiders (Linyphiidae) are an important component of conservation biological control in cereal crops, but they rely on alternative prey when pests are not abundant, such as between cropping cycles. To optimally benefit from these generalist predators, prey choice dynamics must first be understood.Money spiders and their locally available prey were collected from cereal crops 2 weeks pre‐ and post‐harvest. Spider gut DNA was amplified with two novel metabarcoding primer pairs designed for spider dietary analysis, and sequenced.The combined general and spider‐exclusion primers successfully identified prey from 15 families in the guts of the 46 linyphiid spiders screened, whilst avoiding amplification of Erigone spp. The primers show promise for application to the diets of other spider families such as Agelenidae and Pholcidae.Distinct invertebrate communities were identified pre‐ and post‐harvest, and changes in spider diet and, to a lesser extent, prey choice reflected this. Spiders were found to consume one another more than expected, indicating their propensity towards intraguild predation, but also consumed common pest families.Changes in spider prey choice may redress prey community changes to maintain a consistent dietary intake. Consistent provision of alternative prey via permanent refugia should be considered to sustain effective conservation biocontrol. [ABSTRACT FROM AUTHOR]

In certain forensic cases, a quantification of direct‐acting oral anticoagulants (DOACs) can be necessary. We evaluate the applicability of a previously described liquid chromatography–tandem mass spectrometry (LC‐MS/MS) methodology for the determination of DOACs in plasma to postmortem specimen. Postmortem internal quality control (PIQC) samples were prepared in pooled blank postmortem heart blood, femoral blood, cerebrospinal fluid (CSF), and urine as well in plasma. To examine the application of the clinical method to forensic cases, the main validation parameters were reinvestigated using PIQC samples. Postmortem samples of 12 forensic cases with evidence of previous rivaroxaban intake and unknown bleeding disorders were analyzed. Interday variability remained within the acceptance criterion of ±15%. Matrix effects were comparable in blank plasma and postmortem matrix extracts. After 4 weeks of storage in the refrigerator, no relevant decrease of DOACs was evident. After 96 h of storage at room temperature, a slight decrease in edoxaban concentration was observed in CSF and urine, while plasma edoxaban decreased by about 50%. Median (range) rivaroxaban concentrations determined in specimen of forensic cases were as follows: heart blood (n = 6), 17.2 ng/ml (

So far, several publications have discussed the bonding concepts in polyhalides on a theoretical basis. In particular, the trichlorine monoanion is of great interest because its structure should be symmetrical and show two equidistant Cl−Cl bonds. However, apart from matrix‐isolation studies, only asymmetric trichlorine anions have been reported so far. Herein, the trichlorine monoanions in 2‐chloroethyltrimethylammonium trichloride [NMe3EtCl][Cl3], 1, tetramethylammonium trichloride [NMe4][Cl3], 2, and tetrapropylammonium trichloride [NnPr4][Cl3], 3, are analysed. High‐resolution X‐ray structures and experimental charge density analyses supported by periodic quantum‐chemical calculations provide insight into the influence of the crystalline environment on the structure of these [Cl3]− anions as well as into the progress of the bond formation between a dichlorine molecule and a Cl− anion. [ABSTRACT FROM AUTHOR]

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The decreasing number of veteran trees in Europe threatens old‐growth habitats and the fauna they support. This includes rare taxa, such as the violet click beetle, Limoniscus violaceus (Müller, 1821).Samples of wood mould were taken from all beech trees in Windsor Forest previously confirmed to have contained L. violaceus larvae, and from trees where L. violaceus had not previously been detected, the latter categorised as having high, medium or low likelihood of containing the beetle during recent surveys. Habitat characteristics were measured, and volatile profiles determined using gas‐chromatography mass‐spectrometry.Water content significantly differed between tree hollows of different violet click beetle status, high‐potential habitats having higher and relatively stable water content compared with habitats with medium or low potential of beetle occupancy. Several volatile organic compounds (VOCs) were significantly associated with L. violaceus habitats. No differences in other characteristics were detected.The distinction in water regime between habitats highlights that recording this quantitatively could improve habitat surveys. Several potential L. violaceus attractant VOCs were identified. These could potentially be integrated into existing monitoring strategies, such as through volatile‐baited emergence traps or volatile‐based surveying of habitats, for more efficient population monitoring of the beetle. [ABSTRACT FROM AUTHOR]

Thermotropic ionic liquid crystals based on the flavylium scaffold have been synthesized and studied for their structure‐properties relationship for the first time. The mesogens were probed by differential scanning calorimetry (DSC), polarizing optical microscopy (POM), and X‐ray diffraction (XRD). Low numbers of alkoxy side chains resulted in smectic (SmA) and lamello‐columnar (LamCol) phases, whereas higher substituted flavylium salts showed Colro as well as ordered and disordered columnar (Colho, Colhd) mesophases. Mesophase width ranged from 13 K to 220 K, giving access to room temperature liquid crystals. The optical properties of the synthesized compounds were probed towards absorption and emission properties. Strong absorption with maxima between 444 and 507 nm was observed, and some chromophores were highly emissive with quantum yields up to 99 %. Ultimately, mesogenic and dye properties were examined by temperature‐dependent emissive experiments in the solid state. [ABSTRACT FROM AUTHOR]

A new chloronium‐containing salt, [Me2Cl][Al(OTeF5)4], was synthesized on multigram scale by means of a simple one‐pot procedure. The isolated product can be handled at room temperature and used as a strong electrophilic methylation agent. This is demonstrated by the methylation of the very weak bases P(CF3)3, PF3, MeI, and MeBr. [ABSTRACT FROM AUTHOR]

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The reaction of N‐heterocyclic carbenes, 1a–c, towards cyclopentadienes, 2a–c, was studied. N,N′‐diisopropyl‐substituted carbene 1a acts as a Brønsted base and deprotonates cyclopentadiene, 2a, and isopropylcyclopentadiene, 2b, to yield the corresponding imidazolium cyclopentadienide salts, 3a,b, whereas there is no reaction towards 1,2,3,4,5‐pentamethylcyclopentadiene. Imidazolium cyclopentadienide salts, 3a,b, were characterized in solution by 1H and 13C NMR spectroscopy, as well as in the solid state by single‐crystal X‐ray diffraction. In addition, it was demonstrated that imidazolium cyclopentadienide salt 3a can be used as a Cp‐transfer reagent in the synthesis of different cyclopentadienyl transition metal complexes. [ABSTRACT FROM AUTHOR]

The cohesive energy of α‐fluorine, with C2/c space group symmetry, was calculated at benchmark quality by applying the method of increments. The known experimental X‐ray structure data needed to be refined, since the reported intramolecular bond length was unrealistically large. At the CCSD(T) level, including corrections for zero‐point energy, the basis set superposition error, and extrapolated to the complete basis set limit, a cohesive energy of −8.72 kJ mol−1 was calculated, which agrees well with the 0 K‐extrapolated experimental value of −8.35 kJ mol−1. Comparison of the C2/c structure with a Cmca structure, isotypic to that of chlorine, bromine, and iodine reveals that the origin of the different structure of solid fluorine, compared to the heavier halogens, is the lack of significantly stabilizing σ‐hole interactions. In addition, the wave numbers of the stretching mode in solid fluorine were calculated at coupled cluster level and compared to newly recorded Raman spectra of condensed fluorine. Both experiment and calculation indicate a slight up‐shift for the stretching mode by 2 or 5 cm−1, respectively, with respect to a free F2 molecule in the gas phase. Re‐evaluation: State of the art calculations for α‐F2 rectify the crystal structure determined 50 years ago in X‐ray diffraction experiments. With many‐body expansion methods for electron correlation effects, the experimentally known heat of formation is well reproduced and the calculated vibrational frequencies for α‐F2 agree well with newly recorded Raman spectra. [ABSTRACT FROM AUTHOR]

Abstract: For decades the chemistry of polyhalides was dominated by polyiodides and more recently also by an increasing number of polybromides. However, apart from a few structures containing trichloride anions and a single report on an octachloride dianion, [Cl8]2−, polychlorine compounds such as polychloride anions are unknown. Herein, we report on the synthesis and investigation of large polychloride monoanions such as [Cl11]− found in [AsPh4][Cl11], [PPh4][Cl11], and [PNP][Cl11]⋅Cl2, and [Cl13]− obtained in [PNP][Cl13]. The polychloride dianion [Cl12]2− has been obtained in [NMe3Ph]2[Cl12]. The novel compounds have been thoroughly characterized by NMR spectroscopy, single‐crystal Raman spectroscopy, and single‐crystal X‐ray diffraction. The assignment of their spectra is supported by molecular and periodic solid‐state quantum‐chemical calculations. [ABSTRACT FROM AUTHOR]

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The role and use of olfactory cues by penguins is largely under‐investigated, with only a few studies suggesting that odours are involved in prey detection, orientation and for interspecific communication. This also applies to King Penguins Aptenodytes patagonicus where little is known about their chemoreception abilities and, subsequently, the role of odours in their behavioural ecology. Here, we investigated the chemical composition of volatile organic compounds (VOCs) from feathers of King Penguins in the Kerguelen Archipelago and their potential to carry information on identity and sex. We analysed VOCs using direct thermal desorption, a novel approach for extracting volatile compounds directly from solid matrices. We were only able to test at desorption temperatures of 70 and 100 °C to optimize conditions for VOC analysis. We found a profile of 26 VOCs present in most individuals, which varied significantly between individuals but not between sexes. Results suggested that VOCs could possibly be used by King Penguins to locate the colony and recognize individuals, if similar VOCs are also present at ambient conditions. Further studies and behavioural experiments are encouraged to explore olfactory‐based communication in this species. [ABSTRACT FROM AUTHOR]

Abstract: The formation and experimental characterization of the first hexabromide dianion is presented. This dianion fills the last remaining gap in the series of polybromides from the tribromide [Br3]− to the undecabromide [Br11]−. The experimental results are compared to quantum‐chemical calculations. These calculations predict—based on electrostatic interactions—a T‐structure for the hexabromide dianion, while halogen–halogen bonding favors the hockey‐stick‐like structure experimentally found in the crystal structure. The hexabromide is built of two tribromide moieties, one of which is highly asymmetric. The classification of this unique anion as hexabromide dianion is discussed. The counter ion [C5H10N2Br]+ stabilizes the hexabromide dianion by additional σ‐hole interactions. The compound is fully characterized by mass spectrometry, NMR‐, IR and single crystal Raman spectroscopies as well as single‐crystal X‐ray diffraction. [ABSTRACT FROM AUTHOR]

[(C5Me5)FeCl(tmeda)] and the Siemeling "pogo-stick" complex [(C5Me5)FeN(SiMe3)2]. The silylamide [{C5(CHMe2)5}FeN(SiMe3)2] was treated with water to yield the bridged hydroxo dimer [{C5(CHMe2)5}Fe(μ-OH)]2 with high-spin iron(II) configuration. With 2,5-dimethylpyrrole the azaferrocene derivative [{C5(CHMe2)5}Fe(NC4H2Me2-2,5)] was obtained, and with diphenylphosphine a few crystals of the diphosphine hydride [{C5(CHMe2)5}FeH(HPPh2)2] as well as a sample of its dehydrogenative P-P coupling product [{C5(CHMe2)5}FeH(Ph2P-PPh2)]n (n = 1 or 2) have been obtained, which are both diamagnetic 18-valence-electron complexes. Two-coordinated [{C5(CHMe2)5}- FeN(SiMe3)2] features sizeable negative magnetic anisotropy and slow magnetic relaxation with an effective energy barrier for spin reversal of 113 cm-1 under an applied field of 3000 Oe. [ABSTRACT FROM AUTHOR]

Tetramethylammonium tetraiodopentabromide [NMe4][I4Br5] was the first iodobromide to be synthesized and crystallized in an ionic liquid as well as in dichloromethane. The new iodobromides show different structure motives yet are unknown from other nonahalides and can be better described as [(I2Br3)−⋅2 IBr]. The additional IBr units are connected by halogen-halogen interactions on the central V-shaped [I2Br3]−. The characterization was performed by Raman spectroscopy and single crystal X-ray structure determination. Conductivity measurements, thermogravimetric analysis and quantum-chemical calculations completed the structural discussion. [ABSTRACT FROM AUTHOR]

The polybromide salts [BrC(NMe2)2]2[Br8] and [BrC(NMe2)2][Br3] were synthesized in the ionic liquid [BMP][OTf] (1-butyl-1-methyl-pyrrolidinium triflate). The compounds were characterized by Raman, NMR, and X-ray single crystal structure determination as well as quantum-chemical calculations. The polybromide dianion [Br8]2- structure shows similarities to the very recently reported structure of the first octachloride [Cl8]2-. [ABSTRACT FROM AUTHOR]

ABSTRACT Microalgae offer great potential for the industrial production of numerous compounds, but most of the currently available processes fail on economic aspects. Due to the lack of appropriate microcultivation systems, especially screening and early stage laboratory process characterization limit throughput in process development. Consequently, a demand for high throughput photobioreactors has recently been identified upon which some prototype systems emerged. However, compared to microbial microbioreactors, the systems so far introduced suffer from at least one of several drawbacks, that is, inhomogeneous conditions, poor mixing or excessive evaporation. In this context, a microtiter plate based micro-photobioreactor was developed enabling 48-fold parallelized cultivation. Strict control of the process conditions enabled a high comparability between the distinct wells of one plate (±5% fluctuation in biomass formation). The small scale, resulting in a beneficial surface to volume ratio, as well as the fast mixing due to rigorous orbital shaking, ensured an excellent light supply of the cultures. Moreover, non-invasive online biomass quantification was implemented via a scattered light analyzer that is capable of biomass measurements during continuous illumination of the cultures. The system was shown to be especially qualified for parallelized laboratory screening applications like for instance media optimization. Easy automation via integration into a liquid handling platform is given by design. Thereby, the presented micro-photobioreactor system significantly contributes to improving the time efficiency during the development of phototrophic bioprocesses. Biotechnol. Bioeng. 2017;114: 122-131. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Plasmids are common vectors to genetically manipulate Escherichia coli or other microorganisms. They are easy to use and considerable experience has accumulated on their application in heterologous protein production. However, plasmids can be lost during cell growth, if no selection pressure like, e.g., antibiotics is used, hampering the production of the desired protein and endangering the economic success of a biotechnological production process. Thus, in this study the Continuously Operated Shaken BIOreactor System (COSBIOS) is applied as a tool for fast parallel testing of strain stability and operation conditions and to evaluate measures to counter such plasmid loss. In specific, by applying various ampicillin concentrations, the lowest effective ampicillin dosage is investigated to secure plasmid stability while lowering adverse ecological effects. A significant difference was found in the growth rates of plasmid-bearing and plasmid-free cells. The undesired plasmid-free cells grew 30% faster than the desired plasmid-bearing cells. During the testing of plasmid stability without antibiotics, the population fraction of plasmid-bearing cells rapidly decreased in continuous culture to zero within the first 48 h. An initial single dosage of ampicillin did not prevent plasmid loss. By contrast, a continuous application of a low dosage of 10 µg/mL ampicillin in the feed medium maintained plasmid stability in the culture. Consequently, the COSBIOS is an apt reactor system for measuring plasmid stability and evaluating methods to enhance this stability. Hence, decreased production of heterologous protein can be prevented. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1418-1425, 2016 [ABSTRACT FROM AUTHOR]

The polychloride salt [CCl(NMe2)2]+2[Cl8]2− was synthesized and crystallized in the ionic liquid [BMP]OTf. The compound was fully characterized by Raman spectroscopy as well as X-ray single-crystal structure determination, and represents the first example of a polychloride dianion to be described. Detailed gas-phase and solid-state calculations concerning the nature of the bonding situation were also performed. [ABSTRACT FROM AUTHOR]

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Priority effects are known to have a major influence on fungal community development in decomposing wood, but it has not yet been established whether these effects are consistent between different geographical locations. Here, beech ( F agus sylvatica) wood disks that had been pre-colonized with three wood decay basidiomycetes were placed in seven woodland sites with similar characteristics for 12-24 months, and the successor communities profiled using culture-based techniques coupled with amplicon sequencing. On the majority of sites, assembly history differed as a result of primary versus secondary resource capture only (i.e. different communities developed in uncolonized control disks compared with those that had been pre-colonized), but on certain sites distinct successor communities followed each pre-colonizer species. This study provides preliminary evidence that differences in abiotic factors and species pools between sites can cause spatial variation in how priority effects influence wood decay communities. [ABSTRACT FROM AUTHOR]

In a eutectic mixture of two ionic liquids, we have synthesized and crystallized the new polychloride compound [Et4N]2[(Cl3)2·Cl2] that exhibits a periodic 2D polychloride network acting as an anionic layer. Based on its low melting point and vapor pressure, this compound can be described as a room-temperature ionic liquid. The compound was fully characterized by IR and Raman spectroscopy as well as single-crystal X-ray structure determination. The characterization was complemented by solid-state quantum-chemical calculations confirming the results of the experimental work. [ABSTRACT FROM AUTHOR]

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Polyfluoride anions have been investigated by matrix-isolation spectroscopy and quantum-chemical methods. For the first time the higher polyfluoride anion [F5]- has been observed under cryogenic conditions in neon matrices at 850 cm-1. In addition, a new band for the Cs+[F3]- complex in neon is reported. [ABSTRACT FROM AUTHOR]

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Combining classical force fields for the Hartree-Fock (HF) part and the method of increments for post-HF contributions, we calculate the cohesive energy of the ordered and randomly disordered nitrous oxide (N2O) solid. At 0 K, ordered N2O is most favorable with a cohesive energy of −27.7 kJ/mol. At temperatures above 60 K, more disordered structures become compatible and a phase transition to completely disordered N2O is predicted. Comparison with experiment in literature suggests that experimentally prepared N2O crystals are mainly disordered due to a prohibitively high activation energy of ordering processes. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The epidermal organs of an undescribed Phascolion species from the Balearic Islands were investigated using SEM, TEM, LM, CLSM and μ CT methods. We found axial receptor cells confirming the previously assumed sensory function of epidermal organs. Our analyses also revealed six types of secretory cells. Some secretory cells types are capable of secreting filamentous and amorphous secretion in two different ways simultaneously (bimodal secretion). The high diversity of cell types, the complex pattern of acinar units, and the absence of a common gland pore make epidermal organs of Phascolion unique amongst sipunculans ( Phascolion type). Our reconstruction of the evolution of the epidermal organs of Sipuncula revealed that Phascolion-type epidermal organs may have derived from either Golfingia-, Sipunculus- or Phascolosoma-type epidermal organs. The oldest known sipunculans were Golfingia-like and had epidermal organs, which might resemble the architecture of the Golfingia-type epidermal organs in extant taxa. Thus, it can be hypothesized that bimodal secretory cells (e.g. basophilic secretory cells) were part of the sipunculan ground pattern. Moreover, bimodal secretory cells of Phascolion look strikingly similar to those found in various annelid glands and thus might even be part of the ground pattern of stem species of Sipuncula + Pleistoannelida. [ABSTRACT FROM AUTHOR]

Superposition and apposition compound eyes are commonly associated with moths and butterflies, respectively. However, recently intermediate eye designs, combining features of both apposition and superposition eyes were found in tiny insects. Here, we examine the eyes of 12 species of moth, ranging from 1.88 to 6.03 mm body size, by scanning and transmission electron microscopy. Correlations between body and eye sizes are discussed with regard to the eyes' functionality. Although all of the species shared an ommatidial organization characteristic of pterygote insects, three optical designs were found: (a) an apposition eye, (b) an eye resembling apposition eyes, but with a unique crystalline cone, and (c) an eye intermediate in structure between apposition and superposition eyes. Our comparisons also revealed a new type of basal matrix for the Lepidoptera. The results show that in most of the examined compound eyes (with the exception of the apposition eye of Micropterix aruncella), a clear distinction between apposition and superposition eyes is not feasible. Due to functional morphological constraints as a consequence of miniaturization, evolutionary transformations from superposition into apposition optics may have occurred several times independently in various 'microlepidopteran' taxa. The Phyllonorycter medicaginella eye appears to illustrate this evolutionary scenario best. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides are a promising complement to common antibiotics, development of resistance to which is a growing problem. Here we present a de nono-designed peptide, SP1-1 (RKKRLKLLKRLL-NH2), with antimicrobial activity against multiresistant Staphylococcus aureus (minimal inhibitory concentration: 6.25 µM). Elucidation of the mode of action of this peptide revealed a strong interaction with RsbW kinase (Kd: 6.01 ± 2.73 nM), a serine kinase negatively regulating the activity of the transcription factor σB (SigB). SP1-1 binding and functional modulation of RsbW were shown in vitro by a combination of biochemical, molecular, and biophysical methods, which were further genetically evidenced in vivo by analysis of S. aureus ΔsigB deletion mutants. Intracellular localization of the peptide was demonstrated using nanometer-scaled secondary ion mass spectrometry. Moreover, microarray analysis revealed that transcription of numerous genes, involved in cell wall and amino acid metabolism, transport mechanisms, virulence, and pigmentation, is affected. Interestingly, several WaTR binding motif containing genes are induced by SP1-1. In sum, die designed peptide SP1-1 seems to have multiple modes of action, including inhibition of a kinase, and therefore might contribute to the development of new antibacterial compounds, giving bacterial kinase inhibition a closer inspection. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that Chaetognatha represent an evolutionary lineage that is the sister group to all other Protostomia thus promoting these animals as a pivotal model for our understanding of bilaterian evolutionary history. We have analyzed the proliferation of neuronal progenitor cells in the developing ventral nerve center (VNC) of Spadella cephaloptera hatchlings. To that end, for the first time in Chaetognatha, we performed in vivo incorporation experiments with the S-phase specific mitosis marker bromodeoxyuridine (BrdU). Our experiments provide evidence for a high level of mitotic activity in the VNC for ca. 3 days after hatching. Neurogenesis is carried by presumptive neuronal progenitor cells that cycle rapidly and most likely divide asymmetrically. These progenitors are arranged in a distinct grid-like geometrical pattern including about 35 transverse rows. Considering Chaetognaths to be an early offshoot of the protostome lineage we conclude that the presence of neuronal progenitor cells with asymmetric division seems to be a feature that is rooted deeply in the Metazoa. In the light of previous evidence indicating the presence of serially iterated peptidergic neurons with individual identities in the chaetognath VNC, we discuss if these neuronal progenitor cells give rise to distinct lineages. Furthermore, we evaluate the serially iterated arrangement of the progenitor cells in the light of evolution of segmentation. J. Exp. Zool. (Mol. Dev. Evol.) 320B: 179-193, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]