Operation and performance of the Ciba-Corning 512 coagulation monitor during parabolic flight

The goal was to assess the functionality and evaluate the procedures and operations required to operate the Ciba-Corning 512 Coagulation Monitor during parabolic flight. This monitor determines the clotting characteristics of blood. The analyzer operates by laser detection of the cessation of blood flow in a capillary channel within a test cartridge. Test simulator results were excellent for both pre-and post-flight. In-flight results were not obtained due to the warm-up time required for the simulator. Since this is an electronic function only, the expected results on the simulator would be the same in zero-g

PPAR Alpha Regulation of the Immune Response and Autoimmune Encephalomyelitis

PPARs are members of the steroid hormone nuclear receptor superfamily and play an important role in the regulation of lipid metabolism, energy balance, artherosclerosis and glucose control. Recent studies suggest that they play an important role in regulating inflammation. This review will focus on PPAR-α regulation of the immune response. We describe how PPAR-α regulates differentiation of T cells by transactivation and/or interaction with other transcription factors. Moreover, PPAR-α agonists have been shown to ameliorate experimental autoimmune encephalomyelitis (EAE) in mice, suggesting that they could provide a therapy for human autoimmune diseases such as multiple sclerosis

Assessment of pulmonary antibodies with induced sputum and bronchoalveolar lavage induced by nasal vaccination against Pseudomonas aeruginosa: a clinical phase I/II study

<p>Abstract</p> <p>Background</p> <p>Vaccination against <it>Pseudomonas aeruginosa </it>is a desirable albeit challenging strategy for prevention of airway infection in patients with cystic fibrosis. We assessed the immunogenicity of a nasal vaccine based on the outer membrane proteins F and I from <it>Pseudomonas aeruginosa </it>in the lower airways in a phase I/II clinical trial.</p> <p>Methods</p> <p>N = 12 healthy volunteers received 2 nasal vaccinations with an OprF-OprI gel as a primary and a systemic (n = 6) or a nasal booster vaccination (n = 6). Antibodies were assessed in induced sputum (IS), bronchoalveolar lavage (BAL), and in serum.</p> <p>Results</p> <p>OprF-OprI-specific IgG and IgA antibodies were found in both BAL and IS at comparable rates, but differed in the predominant isotype. IgA antibodies in IS did not correlate to the respective serum levels. Pulmonary antibodies were detectable in all vaccinees even 1 year after the vaccination. The systemic booster group had higher IgG levels in serum. However, the nasal booster group had the better long-term response with bronchial antibodies of both isotypes.</p> <p>Conclusion</p> <p>The nasal OprF-OprI-vaccine induces a lasting antibody response at both, systemic and airway mucosal site. IS is a feasible method to non-invasively assess bronchial antibodies. A further optimization of the vaccination schedule is warranted.</p

Biogeochemie von Phosphat im Unterboden am Beispiel deutscher Dauerdüngungsversuche

Unterböden von Ackerstandorten verfügen über große Vorräte an Phosphat (P), allerdings ist nach wie vor unklar, ob, in welchem Umfang und unter welchen Bedingungen diese Nährstoffreserven im Unterboden zur Ernährung unserer Ackerkulturen beitragen. Wir vermuten, dass einerseits langjährige P-Limitierung dazu führen kann, dass mehr P aus dem Unterboden aufgenommen wird, dass aber andererseits die Zugänglichkeit zu P-Reserven im Unterboden auch abhängig ist von der Versorgung mit anderen Nährstoffen, wie z.B. Stickstoff (N) und Kalium (K). Um diese Hypothesen zu testen, beprobten wir unter anderem zwei Statische Nährstoffmangelversuche in Thyrow (Brandenburg) und Gießen (Hessen). Wir entnahmen Bodenproben bis in 100 cm Tiefe, aus Varianten, die seit über 60 Jahren entweder NPK, NK oder PK Düngung erhalten haben. Für diese Proben bestimmten wir die P Pools nach Hedley et al. (1), sowie die Sauerstoffisotopie des Phosphats nach Extraktion mit 1M HCl (δ18OHCl P), welches eine Differenzierung in primäre und sekundäre (d.h. nach vorherigem biologischem Cycling neu ausgefällte) P-Minerale ermöglicht. An beiden Standorten beobachteten wir, dass in den NK-gedüngten Varianten die Vorräte der labilen P Pools aus dem Hedley’schen Extraktionsschema im Unterboden (30 – 100 cm) 10 – 60% geringer waren als in den NPK-gedüngten Varianten. Die Vorräte an HCl P in den NK-Varianten waren jedoch v.a. in Thyrow bis zu 70% höher, während gleichzeitg die δ18OHCl P Werte deutlich niedriger waren als in den NPK-Varianten. Diese niedrigeren Isotopensignaturen deuten auf hauptsächlich primäre P-Minerale hin, sodass wir unsere Annahme von höherem P-Cycling im Unterboden bei Mangel im Oberboden widerrufen müssen. In den PK-gedüngten Varianten beobachteten wir, dass die Vorräte an labilem P im Unterboden 117% (Thyrow) und 22% (Gießen) größer waren als in der NPK-Variante. Dies stützt unsere zweite Annahme von einer Limitierung der P-Aufnahme aus dem Unterboden aufgrund des Mangels an anderen Nährstoffen, allerdings ergaben sich hier keine klaren Auswirkungen auf die δ18OHCl P Signatur des Phosphats. Im Folgenden sollen diese Beobachtungen nun an weiteren Standorten und unter weiteren Einflussparametern getestet werden. Zusammenfassend zeigen jedoch schon unsere bisherigen Ergebnisse, dass die effiziente Ausnutzung von P-Reserven im Unterboden nur unter optimaler Nährstoffversorgung im Oberboden erfolgt

RTL551 Treatment of EAE Reduces CD226 and T-bet+ CD4 T Cells in Periphery and Prevents Infiltration of T-bet+ IL-17, IFN-γ Producing T Cells into CNS

Recombinant T cell receptor ligands (RTLs) that target encephalitogenic T-cells can reverse clinical and histological signs of EAE, and are currently in clinical trials for treatment of multiple sclerosis. To evaluate possible regulatory mechanisms, we tested effects of RTL therapy on expression of pathogenic and effector T-cell maturation markers, CD226, T-bet and CD44, by CD4+ Th1 cells early after treatment of MOG-35-55 peptide-induced EAE in C57BL/6 mice. We showed that 1–5 daily injections of RTL551 (two-domain I-Ab covalently linked to MOG-35-55 peptide), but not the control RTL550 (“empty” two-domain I-Ab without a bound peptide) or Vehicle, reduced clinical signs of EAE, prevented trafficking of cells outside the spleen, significantly reduced the frequency of CD226 and T-bet expressing CD4+ T-cells in blood and inhibited expansion of CD44 expressing CD4+ T-cells in blood and spleen. Concomitantly, RTL551 selectively reduced CNS inflammatory lesions, absolute numbers of CNS infiltrating T-bet expressing CD4+ T-cells and IL-17 and IFN-γ secretion by CNS derived MOG-35-55 reactive cells cultured ex vivo. These novel results demonstrate that a major effect of RTL therapy is to attenuate Th1 specific changes in CD4+ T-cells during EAE and prevent expansion of effector T-cells that mediate clinical signs and CNS inflammation in EAE

PEG Minocycline-Liposomes Ameliorate CNS Autoimmune Disease

Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS). Minocycline, a potent inhibitor of matrix metalloproteinase (MMP)-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG) minocycline liposomes are effective in treating EAE.Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs), we determined that PEG minocycline-liposome preparations stabilized with CaCl(2) are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number.Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS

Engineering pyruvate decarboxylase-mediated ethanol production in the thermophilic host Geobacillus thermoglucosidasius

This study reports the expression, purification, and kinetic characterization of a pyruvate decarboxylase (PDC) from Gluconobacter oxydans . Kinetic analyses showed the enzyme to have high affinity for pyruvate (120 μM at pH 5), high catalytic efficiency (4.75×105 M−1 s−1 at pH 5), a pHopt of approximately 4.5 and an in vitro temperature optimum at approximately 55 °C. Due to in vitro thermostablity (approximately 40 % enzyme activity retained after 30 min at 65 °C), this PDC was considered to be a suitable candidate for heterologous expression in the thermophile Geobacillus thermoglucosidasius for ethanol production. Initial studies using a variety of methods failed to detect activity at any growth temperature (45–55 °C). However, the application of codon harmonization (i.e., mimicry of the heterogeneous host’s transcription and translational rhythm) yielded a protein that was fully functional in the thermophilic strain at 45 °C (as determined by enzyme activity, Western blot, mRNA detection, and ethanol productivity). Here, we describe the first successful expression of PDC in a true thermophile. Yields as high as 0.35±0.04 g/g ethanol per gram of glucose consumed were detected, highly competitive to those reported in ethanologenic thermophilic mutants. Although activities could not be detected at temperatures approaching the growth optimum for the strain, this study highlights the possibility that previously unsuccessful expression of pdcs in Geobacillus spp. may be the result of ineffective transcription/translation coupling.Web of Scienc

The mineralogical composition of calcium and calcium-magnesium carbonate pedofeatures of calcareous soils in the European prairie ecodivision in Hungary

Abstract There is little data on the mineralogy of carbonate pedofeatures in the calcareous soils in Hungary which belong to the European prairie ecodivision. The aim of the present study is to enrich these data. The mineralogical composition of the carbonate pedofeatures from characteristic profiles of the calcareous soils in Hungary was studied by X-ray diffractometry, thermal analysis, SEM combined with microanalysis, and stable isotope determination. Regarding carbonate minerals only aragonite, calcite (+ magnesian calcite) and dolomite (+proto-dolomite) were identified in carbonate grains, skeletons and pedofeatures. The values relating, respectively, to stable isotope compositions (C13, O18) of carbonates in chernozems and in salt-affected soils were in the same range as those for recent soils (latter data reported earlier). There were no considerable differences between the values for the carbonate nodules and tubules from the same horizons, nor were there significant variations between the values of the same pedofeatures from different horizons (BC-C) of the same profile. Thus it can be assumed that there were no considerable changes in conditions of formation. Tendencies were recognized in the changes of (i) carbonate mineral associations, (ii) the MgCO3 content of calcites, (iii) the corrected decomposition temperatures, and (iv) the activation energies of carbonate thermal decompositions among the various substance-regimes of soils. Differences were found in substance-regimes types of soils rather than in soil types