The Temporal Relationship Between Terrestrial Gamma-Ray Flashes and Associated Optical Pulses From Lightning.

We present 221 Terrestrial Gamma-ray Flashes (TGFs) and associated optical pulses observed by the Atmosphere-Space Interactions Monitor (ASIM) on board the International Space Station. The events were detected between the end of March 2019 and November 2020 and consist of X- and gamma-ray energy detections, as well as photometer data (180-230, 337, and 777 nm) and optical camera data (337 and 777 nm). Using the available ASIM data and applying a consistency check based on TGF characteristics and lightning detections from lightning radio atmospherics close in time, we determine the most likely position of the TGFs in relation to the photometer field of view (FoV), and the association to the observed optical pulses. Out of the 221 events we find 72 events where the TGF and optical data are determined to be associated and inside the photometer FoV. Using the measured TGF durations and the time between the onsets of the TGFs and optical pulses we find: (a) That the TGF onsets are always before or at the same time as the optical pulse onsets (taking into account cloud scattering). (b) A tendency for longer duration TGFs to have longer delays between onsets. (c) Two groups of events: (a) where there is a possible overlap between the TGFs and the optical emissions, as the TGFs last longer than the delay between onsets and (b) where the TGFs and optical emissions do not overlap, as there are long delays between the onsets, which cannot be explained by cloud scattering.

Global Distribution of Key Features of Streamer Corona Discharges in Thunderclouds.

We present nighttime worldwide distributions of key features of Blue LUminous Events (BLUEs) detected by the Modular Multispectral Imaging Array of the Atmosphere-Space Interaction Monitor. Around 10% of all detected BLUEs exhibit an impulsive single pulse shape. The rest of BLUEs are unclear (impulsive or not) single, multiple or with ambiguous pulse shapes. BLUEs exhibit two distinct populations with peak power density <25 µWm-2 (common) and ≥25 µWm-2 (rare) with different rise times and durations. The altitude (and depth below cloud tops) zonal distribution of impulsive single pulse BLUEs indicate that they are commonly present between cloud tops and a depth of ≤4 km in the tropics and ≤1 km in mid and higher latitudes. Impulsive single pulse BLUEs in the tropics are the longest (up to ∼4 km height) and have the largest number of streamers (up to ∼3 × 109). Additionally, the analysis of BLUEs has turned out to be particularly complex due to the abundance of radiation belt particles (at high latitudes and in the South Atlantic Anomaly [SAA]) and cosmic rays all over the planet. True BLUEs can not be fully distinguished from radiation belt particles and cosmic rays unless other ground-based measurements associated with the optically detected BLUEs are available. Thus, the search algorithm of BLUEs presented in Soler et al. (2021), https://doi.org/10.1029/2021gl094657 is now completed with a new additional step that, if used, can considerably smooth the SAA shadow but can also underestimate the number of BLUEs worldwide.

Very-high-frequency oscillations in the main peak of a magnetar giant flare.

Magnetars are strongly magnetized, isolated neutron stars1-3 with magnetic fields up to around 1015 gauss, luminosities of approximately 1031-1036 ergs per second and rotation periods of about 0.3-12.0 s. Very energetic giant flares from galactic magnetars (peak luminosities of 1044-1047 ergs per second, lasting approximately 0.1 s) have been detected in hard X-rays and soft γ-rays4, and only one has been detected from outside our galaxy5. During such giant flares, quasi-periodic oscillations (QPOs) with low (less than 150 hertz) and high (greater than 500 hertz) frequencies have been observed6-9, but their statistical significance has been questioned10. High-frequency QPOs have been seen only during the tail phase of the flare9. Here we report the observation of two broad QPOs at approximately 2,132 hertz and 4,250 hertz in the main peak of a giant γ-ray flare11 in the direction of the NGC 253 galaxy12-17, disappearing after 3.5 milliseconds. The flare was detected on 15 April 2020 by the Atmosphere-Space Interactions Monitor instrument18,19 aboard the International Space Station, which was the only instrument that recorded the main burst phase (0.8-3.2 milliseconds) in the full energy range (50 × 103 to 40 × 106 electronvolts) without suffering from saturation effects such as deadtime and pile-up. Along with sudden spectral variations, these extremely high-frequency oscillations in the burst peak are a crucial component that will aid our understanding of magnetar giant flares.

High-Energy Emissions Induced by Air Density Fluctuations of Discharges.

Bursts of X-rays and γ-rays are observed from lightning and laboratory sparks. They are bremsstrahlung from energetic electrons interacting with neutral air molecules, but it is still unclear how the electrons achieve the required energies. It has been proposed that the enhanced electric field of streamers, found in the corona of leader tips, may account for the acceleration; however, their efficiency is questioned because of the relatively low production rate found in simulations. Here we emphasize that streamers usually are simulated with the assumption of homogeneous gas, which may not be the case on the small temporal and spatial scales of discharges. Since the streamer properties strongly depend on the reduced electric field E/n, where n is the neutral number density, fluctuations may potentially have a significant effect. To explore what might be expected if the assumption of homogeneity is relaxed, we conducted simple numerical experiments based on simulations of streamers in a neutral gas with a radial gradient in the neutral density, assumed to be created, for instance, by a previous spark. We also studied the effects of background electron density from previous discharges. We find that X-radiation and γ-radiation are enhanced when the on-axis air density is reduced by more than ∼25%. Pre-ionization tends to reduce the streamer field and thereby the production rate of high-energy electrons; however, the reduction is modest. The simulations suggest that fluctuations in the neutral densities, on the temporal and spacial scales of streamers, may be important for electron acceleration and bremsstrahlung radiation.

Electrochemical functionalization of Au by aminobenzene and 2-aminotoluene.

Au surfaces are functionalized by aminobenzene (AB) and 2-aminotoluene (AT) using the electrochemical reduction of diazotized 1,4-diaminobenzene and 2,5-diaminotoluene. The IR spectroscopic measurements reveal the successful modification of Au surfaces by AB and AT. Both types of layers show similar thicknesses as obtained by microgravimetric measurements via electrochemical quartz crystal microbalance (EQCM). However, the faradaic efficiency for the grafting of AT onto an EQCM-Au sensor was 6% compared to 41% for the grafting of AB. This behavior points to a steric hindrance during the binding of AT to the EQCM surface induced by the additional methyl group present in the toluene derivative. The AB and AT functionalized surfaces have been further modified by the amidation reaction of EDC/NHS activated 4-nitrobenzoic acid. This model system reveals that the amidation reaction is slightly hindered in case of the AT layer due to the presence of the methyl group close to the amino group. This behavior leads to a four times less amount of amide bonds at the AT compared to AB modified Au surfaces as obtained from IR spectroscopic measurements.

[Use of gonadorelin[6-D-Phe] at day 0 or 12 after insemination to increase the conception rate in a large dairy herd in Saxony/Germany]. / Einsatz von Gonadorelin[6-D-Phe] am Tag 0 oder 12 post inseminationem zur Steigerung der Konzeptionsrate in einer sächsischen Milchviehgroßanlage.

OBJECTIVE: To increase conception rates in lactating dairy cows by the application of a gonadotropin-releasing-hormone (GnRH)-agonist after insemination. MATERIAL AND METHODS: A total of 3125 inseminations of 1634 cows were included in this study. The animals were randomized into three groups at the time of insemination (day 0) using the final numeral of the ear-tag number: The cows of the GnRH0 group were treated using 100 µg gonadorelin[6-D-Phe] intramuscularly immediately after insemination (day 0), while those of the GnRH12 group were treated similarly at day 12. The cows of the control group received no hormonal treatment after insemination. An examination for pregnancy was performed at day 28 using transrectal ultrasonography. Analysis of the data sets was conducted for the number of inseminations (NI) 1-4 and for the last observed insemination of the respective cow during the experimental period, respectively. In a second step, statistical analysis was performed for the first service of cows with a lactation number of 1 versus > 1, with emphasis on the daily milk yield. In addition, a metritis diagnosed after the previous parturition was investigated as a possible factor influencing NI 1. RESULTS: Pregnancy risk at day 28 was decreased for NI 2 (n = 792) in the GnRH0 group compared to the control group (odds ratio [OR] = 0.69; 95% confidence interval [CI95] = 0.5-1.0; p = 0.04). A similar observation was found for NI 3 (n = 495) for the GnRH12 group (OR = 0.54; CI95 = 0.3-0.9; p = 0.01). In contrast, the pregnancy risk was increased for cows with a lactation number ≥ 2 and with a daily milk yield ≥ 42.5 kg (7-day-mean at day 0) at the first service (n = 364) by treatment with gonadorelin immediately after insemination (OR = 2.0; CI95 = 1.2-3.4; p = 0.01). No significant differences in the pregnancy risk were observed for the remaining analysed classes. CONCLUSION: An increased conception rate was only achieved for the first service of high-yield dairy cows (lactation number ≥ 2) by gonadorelin treatment at day 0. Presumably, the higher incidence of delayed ovulations in this group was treated successfully by gona- dorelin administration.

Comparison of commercially available target enrichment methods for next-generation sequencing.

Isolating high-priority segments of genomes greatly enhances the efficiency of next-generation sequencing (NGS) by allowing researchers to focus on their regions of interest. For the 2010-11 DNA Sequencing Research Group (DSRG) study, we compared outcomes from two leading companies, Agilent Technologies (Santa Clara, CA, USA) and Roche NimbleGen (Madison, WI, USA), which offer custom-targeted genomic enrichment methods. Both companies were provided with the same genomic sample and challenged to capture identical genomic locations for DNA NGS. The target region totaled 3.5 Mb and included 31 individual genes and a 2-Mb contiguous interval. Each company was asked to design its best assay, perform the capture in replicates, and return the captured material to the DSRG-participating laboratories. Sequencing was performed in two different laboratories on Genome Analyzer IIx systems (Illumina, San Diego, CA, USA). Sequencing data were analyzed for sensitivity, specificity, and coverage of the desired regions. The success of the enrichment was highly dependent on the design of the capture probes. Overall, coverage variability was higher for the Agilent samples. As variant discovery is the ultimate goal for a typical targeted sequencing project, we compared samples for their ability to sequence single-nucleotide polymorphisms (SNPs) as a test of the ability to capture both chromosomes from the sample. In the targeted regions, we detected 2546 SNPs with the NimbleGen samples and 2071 with Agilent's. When limited to the regions that both companies included as baits, the number of SNPs was ∼1000 for each, with Agilent and NimbleGen finding a small number of unique SNPs not found by the other.

Detection and correction of interference in SRM analysis.

Selected Reaction Monitoring (SRM) is a method of choice for accurate quantitation of low-abundance proteins in complex backgrounds. This strategy is, however, sensitive to interference from other components in the sample that have the same precursor and fragment masses as the monitored transitions. We present here an approach to detect interference by using the expected relative intensity of SRM transitions. We also designed an algorithm to automatically detect the linear range of calibration curves. These approaches were applied to the experimental data of Clinical Proteomic Tumor Analysis Consortium (CPTAC) Verification Work Group Study 7 and show that the corrected measurements provide more accurate quantitation than the uncorrected data.

Microbiological risk of anaesthetic breathing circuits after extended use.

INTRODUCTION: Daily change of breathing circuits in the operating theatre requires a lot of resources and is time and labour consuming. The extended use of breathing circuits could reduce the workload of the staff and health care costs. The aim of the present study was to evaluate the contamination rate of anaesthesia breathing circuits changed after 24, 48 or 72 h of use. MATERIALS: The study was performed as an experimental observational study. Microbiological samples were taken from 112 breathing systems including both parts of the ventilator circuit (inspiration and expiration) and analysed using microbiological standard techniques. Breathing circuits were changed according to three different schedules. In the 24-h group, breathing circuits were changed every day, whereas in the 48-h group changing of the circuits took place on Mondays, Wednesdays and Fridays. A period of 72 h operating use was tested on weekends. RESULTS: A total of 112 breathing systems comprised of 224 samples from the ventilator circuit were tested for bacteria and yeast contamination. A non-significant increase in the contamination rate was observed with the extended use for breathing circuits (24 h: 3.33%, 48 h: 4.35% and 72 h: 5.56%; P for trend=0.66). Similarly, no significant increase in contamination rate could be observed at the sample level (24 h: 1.67%, 48 h: 3.26% and 72 h: 2.78%; P for trend=0.71). CONCLUSION: The extended use of breathing circuits for 48 and 72 h does not increase significantly the risk of contamination, provided that HME filters are changed separately for every patient.

[Instituting a surgical skills lab at a training hospital]. / Einrichtung eines chirurgischen Trainingslabors an einer Ausbildungsklinik.

The improvement of surgical skills of trainees in Germany often occurs solely in the operating room. In recent years, several countries have established surgical skills labs as an essential part of surgical education, with the goal of improving and refining surgical skills before clinical application. Several years ago, training units were established by the industry wherein the curricula focused on products of the respective company. Selected training courses are still offered in a few clinics. Presently, laboratories which train the surgical skills of novices in an individually adapted form are lacking. A surgical skills lab with a comprehensive curriculum of training courses was introduced at the University Hospital of Marburg in 2005. The present article describes the development and introduction of such facilities. The authors are convinced that surgical skills labs will become increasingly important in German surgical education for improving patient safety in the operating room.

[How do general surgery patients experience the intensive care unit? Results of a prospective observational study]. / Wie erleben allgemeinchirurgische Patienten die Intensivstation? Ergebnisse einer prospektiven Beobachtungsstudie.

INTRODUCTION: Subjective experiences of patients during their stay in the intensive care unit (ICU) have so far rarely been described. The aim of this study was to analyze the experiences of patients during their stay in the ICU. METHODS: In a prospective study, 100 general surgical ICU patients were recorded consecutively. A questionnaire that covered a broad range of possible ICU experiences was handed out to patients shortly following their stay in ICU. At the same time, a questionnaire was given to the personnel of the ICU to investigate how well nurses and doctors were able to adopt the patients' perspectives of the ICU experience. RESULTS: Concerning the physical symptoms, insomnia was to the fore (67% of patients). Despite pain medication, 25% of patients reported severe pain. The main psychological symptom was a feeling of helplessness (29% of patients). As a general cause for concern, 48% of patients complained about limited mobility. The patients were critical of the presence of severely ill patients. The standards of nursing and medical attention, however, were judged very positively. The evaluation of the staff differed from the patients' experiences in many respects; the clearest differences concerned the items of pain, sleeping disorders and the observance of privacy. CONCLUSIONS: The study results led to several practical consequences in the quality of management procedure (e.g., the introduction of a thorough night's rest at the ICU, optimized information for patients). Additionally, we initiated further studies concerning the quality of life of ICU patients.

Uroplakin Ia is the urothelial receptor for uropathogenic Escherichia coli: evidence from in vitro FimH binding.

The binding of uropathogenic Escherichia coli to the urothelial surface is a crucial initial event for establishing urinary tract infection because it allows the bacteria to gain a foothold on the urothelial surface, thus preventing them from being removed by micturition. In addition, it triggers bacterial invasion as well as host urothelial defense. This binding is mediated by the FimH adhesin located at the tip of the bacterial type 1-fimbrium, a filamentous attachment apparatus, and its urothelial receptor. We have prepared a biotinylated, recombinant FimH-FimC adhesin:chaperone complex and used it to identify its mouse urothelial receptor. The FimH-FimC complex binds specifically to a single 24 kDa major mouse urothelial plaque protein, which we identified as uroplakin Ia by mass spectrometry, cDNA cloning and immunoreactivity. The terminal mannosyl moieties on Asn-169 of uroplakin Ia are responsible for FimH as well as concanavalin A binding. Although FimH binds to uroplakin Ia with only moderate strength (K(d) approximately 100 nM between pH 4 and 9), the binding between multiple fimbriae of a bacterium and the crystalline array of polymerized uroplakin receptors should achieve high avidity and stable bacterial attachment. The FimH-FimC complex binds preferentially to the mouse urothelial umbrella cells in a pattern similar to uroplakin staining. Our results indicate that the structurally related uroplakins Ia and Ib are glycosylated differently, that uroplakin Ia serves as the urothelial receptor for the type 1-fimbriated E. coli, and that the binding of uropathogenic bacteria to uroplakin Ia may play a key role in mediating the urothelial responses to bacterial attachment.

Cutting edge: positive selection induced by a self-peptide with TCR antagonist activity.

Antagonist-like engagement of the TCR has been proposed to induce T cell selection in the thymus. However, no natural TCR ligand with TCR antagonist activity is presently known. Using a combination of bioinformatics and functional testing we identified the first self-peptide that can both deliver antagonist-like signals and promote T cell selection in the thymus. The peptide is presented by appropriate MHC class I molecules in vivo. Thus, endogenous antagonist peptides exist and may be involved in TCR repertoire selection.

Characterization of phosphopeptides from protein digests using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and nanoelectrospray quadrupole time-of-flight mass spectrometry.

A two-step mass spectrometric method for characterization of phosphopeptides from peptide mixtures is presented. In the first step, phosphopeptide candidates were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) based on their higher relative intensities in negative ion MALDI spectra than in positive ion MALDI spectra. The detection limit for this step was found to be 18 femtomoles or lower in the case of unfractionated in-solution digests of a model phosphoprotein, beta-casein. In the second step, nanoelectrospray tandem mass (nES-MS/MS) spectra of doubly or triply charged precursor ions of these candidate phosphopeptides were obtained using a quadrupole time-of-flight (Q-TOF) mass spectrometer. This step provided information about the phosphorylated residues, and ruled out nonphosphorylated candidates, for these peptides. After [(32)P] labeling and reverse-phase high-performance liquid chromatography (RP-HPLC) to simplify the mixtures and to monitor the efficiency of phosphopeptide identification, we used this method to identify multiple autophosphorylation sites on the PKR-like endoplasmic reticulum kinase (PERK), a recently discovered mammalian stress-response protein.

Systemic amyloid deposits in familial British dementia.

Familial British dementia (FBD) is an early onset inherited disorder that, like familial Alzheimer's disease (FAD), is characterized by progressive dementia, amyloid deposition in the brain, and neurofibrillary degeneration of limbic neurons. The primary structure of the amyloid subunit (ABri) extracted from FBD brain tissues (Vidal, R., Frangione, B., Rostagno, A., Mead, S., Revesz, T., Plant, G., and Ghiso, J. (1999) Nature 399, 776-781) is entirely different and unrelated to any previously known amyloid protein. Patients with FBD have a single nucleotide substitution at codon 267 in the BRI2 gene, resulting in an arginine replacing the stop codon and a longer open reading frame of 277 amino acids instead of 266. The ABri peptide comprises the 34 C-terminal residues of the mutated precursor ABriPP-277 and is generated via furin-like proteolytic processing. Here we report that carriers of the Stop-to-Arg mutation have a soluble form of the amyloid peptide (sABri) in the circulation with an estimated concentration in the range of 20 ng/ml, several fold higher than that of soluble Abeta. In addition, ABri species identical to those identified in the brain were also found as fibrillar components of amyloid deposits predominantly in the blood vessels of several peripheral tissues, including pancreas and myocardium. We hypothesize that the high concentration of the soluble de novo created amyloidogenic peptide and/or the insufficient tissue clearance are the main causative factors for the formation of amyloid deposits outside the brain. Thus, FBD constitutes the first documented cerebral amyloidosis associated with neurodegeneration and dementia in which the amyloid deposition is also systemic.

Definitive identification of mammalian 5-hydroxymethyluracil DNA N-glycosylase activity as SMUG1.

Purification from calf thymus of a DNA N-glycosylase activity (HMUDG) that released 5-hydroxymethyluracil (5hmUra) from the DNA of Bacillus subtilis phage SPO1 was undertaken. Analysis of the most purified fraction by SDS-polyacrylamide gel electrophoresis revealed a multiplicity of protein species making it impossible to identify HMUDG by inspection. Therefore, we renatured the enzyme after SDS-polyacrylamide gel electrophoresis and assayed slices of the gel for DNA N-glycosylase activity directed against 5hmUra. Maximum enzymatic activity was identified between molecular mass markers 30 and 34 kDa. Protein was extracted from gel slices and subjected to tryptic digestion and analysis by mass spectrometry. Analysis revealed the presence of 11 peptides that were homologous or identical to the sequence of the recently characterized human single-stranded monofunctional uracil DNA N-glycosylase (hSMUG1). The cDNA of hSMUG1 was isolated and expressed as a recombinant glutathione S-transferase fusion protein that was shown to release 5hmUra with 20x the specific activity of the most purified bovine fraction. We conclude that hSMUG1 and HMUDG are the same protein.

Enantioselective construction of cyclic quaternary centers: (-)-mesembrine.

The preparation of the crystalline amide 2 is reported. Conjugate addition to 2 proceeded with the expected high diastereocontrol to give 3. This set the stage for subsequent intramolecular alkylidene C-H insertion to give, after ozonolysis and aldol condensation, (-)-mesembrine 1. Amide 2 should be a useful chiron for the enantioselective construction of cyclic quaternary centers.

The effect of recombinant recoverin on the photoresponse of truncated rod photoreceptors.

Recoverin is a heterogeneously acylated calcium-binding protein thought to regulate visual transduction. Its effect on the photoresponse was investigated by dialyzing the recombinant protein into truncated salamander rod outer segments. At high Ca2+ (Ca), myristoylated recoverin (Ca-recoverin) prolonged the recovery phase of the bright flash response but had less effect on the dim flash response. The prolongation of recovery had an apparent Kd for Ca of 13 microM and a Hill coefficient of 2. The prolongation was shown to be mediated by inhibition of rhodopsin deactivation. After a sudden imposed drop in Ca concentration, the effect of recoverin switched off with little lag. The myristoyl (C14:0) modification of recoverin increased its activity 12-fold, and the C12:0 or C14:2 acyl group gave similar effects. These experiments support the notion that recoverin mediates Ca-dependent inhibition of rhodopsin phosphorylation and thereby controls light-triggered phosphodiesterase activity, particularly at high light levels.

Functional heterogeneity of transducin alpha subunits.

The N-terminal glycine of transducin alpha subunits is acylated by lauroyl (C12:0), myristoyl (C14:0), (cis-delta5)-tetradecaenoyl (C14:1) or (cis,cis-delta5,delta8)-tetradecadienoyl (C14:2) fatty acyl groups. We examined functional heterogeneity of transducin by sequentially eluting it from bleached outer segments using increasing concentrations of GTP then identifying the N-terminal acyl groups on the eluted alpha subunits. C14:2 acylated transducin eluted at low GTP concentrations followed by C12:0, C14:1 and C14:0 transducin at higher GTP concentrations. This suggests functional heterogeneity in the different forms of transducin alpha subunits.