Gamma Ray Glow Observations at 20-km Altitude.

In the spring of 2017 an ER-2 aircraft campaign was undertaken over continental United States to observe energetic radiation from thunderstorms and lightning. The payload consisted of a suite of instruments designed to detect optical signals, electric fields, and gamma rays from lightning. Starting from Georgia, USA, 16 flights were performed, for a total of about 70 flight hours at a cruise altitude of 20 km. Of these, 45 flight hours were over thunderstorm regions. An analysis of two gamma ray glow events that were observed over Colorado at 21:47 UT on 8 May 2017 is presented. We explore the charge structure of the cloud system, as well as possible mechanisms that can produce the gamma ray glows. The thundercloud system we passed during the gamma ray glow observation had strong convection in the core of the cloud system. Electric field measurements combined with radar and radio measurements suggest an inverted charge structure, with an upper negative charge layer and a lower positive charge layer. Based on modeling results, we were not able to unambiguously determine the production mechanism. Possible mechanisms are either an enhancement of cosmic background locally (above or below 20 km) by an electric field below the local threshold or an enhancement of the cosmic background inside the cloud but then with normal polarity and an electric field well above the Relativistic Runaway Electron Avalanche threshold.

A role for miR-132 in learned safety.

Learned safety is a fear inhibitory mechanism, which regulates fear responses, promotes episodes of safety and generates positive affective states. Despite its potential as experimental model for several psychiatric illnesses, including post-traumatic stress disorder and depression, the molecular mechanisms of learned safety remain poorly understood, We here investigated the molecular mediators of learned safety, focusing on the characterization of miRNA expression in the basolateral amygdala (BLA). Comparing levels of 22 miRNAs in learned safety and learned fear trained mice, six safety-related miRNAs, including three members of the miR-132/-212 family, were identified. A gain-of-function approach based upon in-vivo transfection of a specific miRNA mimic, and miR-132/212 knock-out mice as loss-of-function tool were used in order to determine the relevance of miR-132 for learned safety at the behavioral and the neuronal functional levels. Using a designated bioinformatic approach, PTEN and GAT1 were identified as potential novel miR-132 target genes and further experimentally validated. We here firstly provide evidence for a regulation of amygdala miRNA expression in learned safety and propose miR-132 as signature molecule to be considered in future preclinical and translational approaches testing the transdiagnostic relevance of learned safety as intermediate phenotype in fear and stress-related disorders.

Optimizing and extending light-sculpting microscopy for fast functional imaging in neuroscience.

A number of questions in system biology such as understanding how dynamics of neuronal networks are related to brain function require the ability to capture the functional dynamics of large cellular populations at high speed. Recently, this has driven the development of a number of parallel and high speed imaging techniques such as light-sculpting microscopy, which has been used to capture neuronal dynamics at the whole brain and single cell level in small model organisms. However, the broader applicability of light-sculpting microcopy is limited by the size of volumes for which high speed imaging can be obtained and scattering in brain tissue. Here, we present strategies for optimizing the present tradeoffs in light-sculpting microscopy. Various scanning modalities in light-sculpting microscopy are theoretically and experimentally evaluated, and strategies to maximize the obtainable volume speeds, and depth penetration in brain tissue using different laser systems are provided. Design-choices, important parameters and their trade-offs are experimentally demonstrated by performing calcium-imaging in acute mouse-brain slices. We further show that synchronization of line-scanning techniques with rolling-shutter read-out of the camera can reduce scattering effects and enhance image contrast at depth.

Identification of hepatic transcriptional changes in insulin-resistant rats treated with peroxisome proliferator activated receptor-alpha agonists.

Peroxisome proliferator activated receptor (PPAR)-alpha controls the expression of multiple genes involved in lipid metabolism, and activators of PPAR-alpha, such as fibrates, are commonly used drugs in the treatment of hypertriglyceridemia and other dyslipidemic states. Recent data have also suggested a role for PPAR-alpha in insulin resistance and glucose homeostasis. In the present study, we have assessed the transcriptional and physiological responses to PPAR-alpha activation in a diet-induced rat model of insulin resistance. The two PPAR-alpha activators, fenofibrate and Wy-14643, were dosed at different concentrations in high-fat fed Sprague-Dawley rats, and the transcriptional responses were examined in liver using cDNA microarrays. In these analyses, 98 genes were identified as being regulated by both compounds. From this pool of genes, 27 correlated to the observed effect on plasma insulin, including PPAR-alpha itself and the leukocyte antigen-related protein tyrosine phosphatase (PTP-LAR). PTP-LAR was downregulated by both compounds, and showed upregulation as a result of the high-fat feeding. This regulation was also observed at the protein level. Furthermore, downregulation of PTP-LAR by fenofibric acid was demonstrated in rat FaO hepatoma cells in vitro, indicating that the observed regulation of PTP-LAR by fenofibrate and Wy-14643 in vivo is mediated as a direct effect of the PPAR agonists on the hepatocytes. PTP-LAR is one of the first genes involved in insulin receptor signaling to be shown to be regulated by PPAR-alpha agonists. These data suggest that factors apart from skeletal muscle lipid supply may influence PPAR-alpha-mediated amelioration of insulin resistance.

[Immune electrophoretic investigations about the interaction of different dyes with the beta-2-glycoprotein I (author's transl)]. / Immunelektrophoretische Untersuchungen zur Wechselwirkung verschiedener Farbstoffe mit dem beta-2-Glykoprotein I.

A changed electrophoretical mobility of beta-2-glycoprotein I in presence of 24 dyes could be established by means of immuno-electrophoresis. It is seen as an expression of interaction of this protein with different small molecules.

Polycyclic aromatic hydrocarbons in rainwater.

A study on polycyclic aromatic hydrocarbons (PAH) in rainwater was carried out over periods of at least one year at two locations in Belgium with different environments. Maximum amounts and concentrations of PAH were reached during the winter period, mainly due to household heating. This influence was also reflected in the relative proportions of the six PAH measured. For comparable periods the amounts of PAH were almost proportional to the quantity of rain. With the available data, and as most of the rainfall is coming from the same wind direction, it was not feasible to localise possible pollution sources based upon the distribution of PAH over the different windsectors, nor was it possible to identify significant differences for both sampling locations due to their different surroundings, indicating that the rain plays an important role in the transport and distribution of pollutants over a wide area. Between about 100 and 170 micrograms m-2 PAH and 2 to 3 g m-2 of total organic carbon content (TOC) per year were deposited by the rain, corresponding to mean concentrations of about 140 ngl-1 of PAH and 2.9 mgl-1 of TOC.

Changes of plasma fibronectin concentration and phagocytic activity in immunosuppressed patients during selective decontamination.

Plasma fibronectin and phagocytic activity play important roles in combating infections. The question is discussed, whether both defense systems are also of importance in immunosuppressed patients. Further, the behaviour of plasma fibronectin determined by laser nephelometry, and phagocytic activity determined by chemiluminescence is demonstrated in patients with leukaemia under the conditions of selective decontamination of the intestinal tract. The following results are shown: Plasma fibronectin concentration decreases 10 to 14 days before onset of the first clinical signs of an infection. Plasma fibronectin level changes appear earlier than that of C-reactive protein (Crp). Therefore, it is suitable as a parameter for assessment of the course of an infection. Decreased plasma fibronectin levels occurring over longer periods have to be regarded as unfavourable prognostic criterion. The phagocytic activity of immunosuppressed patients selectively decontaminated is significantly below that of healthy adults. A clear assignment of phagocytic activity to the clinical picture, the number of granulocytes and plasma fibronectin level is not possible at present. Additional studies are necessary. Both plasma fibronectin level and phagocytic activity do not appear to be influenced by selective decontamination of the intestinal tract.

Changes of immunological parameters in immunocompromised patients under selective decontamination of the digestive tract. Second Part: Investigations on the influence of drugs on zymosan-induced and luminol-enhanced chemiluminescence of peripheral leucocytes.

The influence of drugs used for selective decontamination, given in therapeutically effective concentrations, was examined in healthy controls and immunocompromised patients with hematologic systemic diseases by measuring the zymosan-induced and luminol-enhanced chemiluminescence of peripheral leucocytes. Drug-induced repression of phagocytic activity could usually be found both in healthy controls and in patients with hematologic systemic diseases. The combination of trimethoprim and sulfamerazine had a pronounced repressive effect. Such indications should be taken as a basis for further investigations in order to avoid additional iatrogenic restriction of defence. If possible, drugs with effects leading to repression of phagocytosis should not be used for selective decontamination.

Changes of immunological parameters in immunocompromised patients under selective decontamination of the digestive tract. Third Part: Behaviour of some plasma proteins.

We studied the importance of changes in plasma protein concentrations in patients with hematologic systemic diseases treated by selective decontamination of the digestive tract. The concentrations of albumin, acute-phase proteins, immunoglobulins and fibronectin were determined by laser nephelometry in 125 serum samples of eight patients. Results obtained allow the following conclusions: 1. There was a correlation between the clinical condition and concentrations of acid alpha-1-glycoprotein, IgG, CRP and fibronectin. These concentrations might be important for assessment of the course of the disease, effectiveness of therapy and the detection of pathogenetic relations. 2. The acid alpha-1-glycoprotein is of particular importance since relations exist between changes in its concentration and therapeutic results as well as the prognosis of the disease.

A validated analytical method for the determination of perfluorinated compounds in surface-, sea- and sewagewater using liquid chromatography coupled to time-of-flight mass spectrometry.

Perfluorinated compounds (PFCs), which are extensively used in a wide variety of applications because of their specific surfactant properties, have recently appeared as an important new class of global environmental pollutants. Quantitative analysis of PFCs in aqueous matrices remains, however, a challenging task. During this study, a new analytical method for the determination of 14 PFCs in surface-, sewage- and seawater was developed and validated. The target analytes were extracted using solid-phase extraction followed by liquid chromatography coupled to a time-of-flight mass spectrometer (LC-ToF-MS). The use of very narrow mass tolerance windows (< 10 ppm) resulted in a highly selective MS-technique for the detection of PFCs in complex aqueous matrices. Validation of this analytical method in surface-, sewage- and seawater resulted in limits of quantification (LOQs) varying from 2 to 200 ng L⁻¹, satisfying recoveries (92-134%), and good linearity (R²=0.99 for most analytes). Analysis of samples of the North Sea, the Scheldt estuary, and three harbours of the Belgian coastal region led to the detection of four different PFCs. Perfluorooctane sulfonate (PFOS) was found to be the most abundant PFC in levels up to 38.9 ng L⁻¹.

Fractional magnetization plateaus and magnetic order in the Shastry-Sutherland magnet TmB4.

We investigate the phase diagram of TmB4, an Ising magnet on a frustrated Shastry-Sutherland lattice, by neutron diffraction and magnetization experiments. At low temperature we find Néel order at low field, ferrimagnetic order at high field, and an intermediate phase with magnetization plateaus at fractional values M/M_(sat)=1/7,1/8,1/9,... and spatial stripe structures. Using an effective S=1/2 model and its equivalent two-dimensional fermion gas we suggest that the magnetic properties of TmB4 are related to the fractional quantum Hall effect of a 2D electron gas.

[The binding of dyes of fibrinogen]. / Untersuchungen über die Bindung von Farbstoffen an Fibrinogen.

Examinations performed by means of the agargel-electrophoresis, immunoelectrophoresis, discelectrophoresis, and chromatography on gel in human plasma and preparations of fibrinogen revealed that fibrinogen will form complexes with 18 examined dyes of different chemical structure, from a total amounting to 46. The findings indicate a marked affinity of fibrinogen towards small molecules in general. In nearly all complex forming colour materials, fibrinogen could be identified by immunodiffusion in the colour-blood supernatant liquid. The physiological significance of the binding capacity of fibrinogen is discussed.

[Comparative study on lymphocyte stimulation by PHA and bacterial endotoxins, particularly in malignant tumor and allergy patients]. / Vergleichende Untersuchungen zur Lymphozytenstimulation durch PHA und bakterielle Endotoxine, insbesondere bei Patienten mit bösartigen Geschwülsten und Allergie

In a group of 37 tumor patients with predominantly advanced disease, LPS stimulation (LPS of Sh. sonnei and Sh. flexneri) resulted in a significant increase of the transformation rates caused, most probably, by the high proportion of B cells. On the other hand, allergics (drug allergies) did not differ from controls. It seems possible that B cell stimulation by bacterial endotoxins can be used for the assessment of the reactivity of the organism.

[Early diagnosis of primary chronic glomerulonephritis in the latency stage]. / Frühdiagnostik primär chronischer Glomerulonephritiden im Stadium der Latenz.

In 74 of 195 patients with isolated proteinuria and/or haematuria investigated by means of renal biopsy laser-nephelometric determinations of the concentrations of albumin, alpha2-macroglobulin, transferrin, IgG, IgA and IgM in the urine were performed. Their result was that patients with chronic interstitial nephritis or chronic glomerulonephritis by increased concentration of albumin, transferrin, IgG and IgA statistically ascertained differ from patients with normal renal tissue or slight glomerular abnormalities.

[Investigation on the detection of circulating antibodies in yoshida-sarcoma bearing rats by the serologic-nephelometric method of Hoigné (author's transl)]. / Untersuchungen zum Nachweis zirkulierender Antikörper bei Yoshida-Sarkom-tragenden Ratten mit der serologisch-nephelometrischen methode nach Hoigné.

Circulating antibodies against tumour antigens were detected by means of the serologic-nephelometric method of Hoigné et al. (1955). Under employment of homogenates of tumour tissue as antigen solutions in 95 per cent of the cases the sera of Yoshida-sarcoma bearing rats reacted positively, while only in 4 per cent of the normal animals a positive reaction was found. 11 per cent of tumour-bearing animals showed in addition positive reactions against the normal muscle tissue, normal rats reacted positively in 2 per cent of the cases. In 93 per cent the sera of tumour-bearing animals reacted with spleen homogenates of sarcoma-bearing rats positively, whereas serum of normal rats showed 20 per cent positive reactions with the same antigen. The results confirm the aptitude of the serologicnephelometric method of Hoigné et al. (1955) and of the employed animal model for investigations of tumour-immunological problems, and they underline the antigenicity of the Yoshida-sarcoma.

Ether derivatives of alpha-amanitin. Introduction of spacer moieties, lipophilic residues, and radioactive labels.

Etherification of alpha-amanitin with tritiated methyl iodide yielded a radioactively labeled amatoxin of high specific activity (similar to or approximately 4 Ci/mmol) which, in its inhibition capacity for RNA polymerase II, was very similar to alpha-amanitin. The labeled toxin was used successfully in binding assays with RNA polymerases II and in radioimmunological determinations of amatoxins. If long-chained alkyl bromides were reacted with alpha-amanitin, lipophilic ether derivatives were obtained with a facilitated penetration capacity into cells. As a consequence of the improved permeability, two derivatives, O-hexyl- and O-decyl-alpha-amanitin, were more toxic in vivo than alpha-amanitin, although their affinity to RNA polymerases II was much reduce. By reaction of N-tert-butyloxy-carbonyl-N'-(6-bromocaproyl)ethylenediamine with alpha-amanitin, a ten-atom spacer with a terminal amino group could be introduced into the toxin, which allowed the attachment of alpha-amanitin to proteins, solid-phase supports, or reporter groups. For example, by reaction with fluoresceinyl isothiocyanate, a fluorescent amatoxin was prepared for visualizing amatoxin-binding structures in cells. After succinylation of the spacer moiety, alpha-amanitin could be attached to proteins, e.g., fetuin, yielding a derivative with good antigenic properties. When an alpha-amanitin derivative was coupled to Sepharose 6B, an adsorbent for affinity chromatography was obtained suitable for a one-step purification of amatoxin-binding immunoglobulins from the sera of immunized rabbits.