The Effects of Gas Saturation of Electrolytes on the Performance and Durability of Lithium‐Ion Batteries

Traces of species in batteries are known to impact battery performance. The effects of gas species, although often reported in the electrolyte and evolving during operation, have not been systematically studied to date and are therefore barely understood. This study reveals and compares the effects of different gases on the charge-discharge characteristics, cycling stability and impedances of lithium-ion batteries. All investigated gases have been previously reported in lithium-ion batteries and are thus worth investigating: Ar, CO$_{2}$, CO, C$_{2}$H$_{4}$, C$_{2}$H$_{2}$, H$_{2}$, CH$_{4}$ and O$_{2}$. Gas-electrolyte composition has a significant influence on formation, coulombic and energy efficiencies, C-rate capability, and aging. Particularly, CO$_{2}$ and O$_{2}$ showed a higher C-rate capability and a decrease in irreversible capacity loss during the first cycle compared to Ar. Similar discharge capacities and aging behaviors are observed for CO, C$_{2}$H$_{4}$ and CH$_{4}$. Acetylene showed a large decrease in performance and cycle stability. Furthermore, electrochemical impedance spectroscopy revealed that the gases mainly contribute to changes in charge transfer processes, whereas the effects on resistance and solid electrolyte interphase performance were minor. Compared to all other gas–electrolyte mixtures, the use of CO$_{2}$ saturated electrolyte showed a remarkable increase in all performance parameters including lifetime

Inhibition of Allogeneic T Cell Proliferation by Indoleamine 2,3-Dioxygenase–expressing Dendritic Cells: Mediation of Suppression by Tryptophan Metabolites

Indoleamine 2,3-dioxygenase (IDO), an enzyme involved in the catabolism of tryptophan, is expressed in certain cells and tissues, particularly in antigen-presenting cells of lymphoid organs and in the placenta. It was shown that IDO prevents rejection of the fetus during pregnancy, probably by inhibiting alloreactive T cells, and it was suggested that IDO-expression in antigen-presenting cells may control autoreactive immune responses. Degradation of tryptophan, an essential amino acid required for cell proliferation, was reported to be the mechanism of IDO-induced T cell suppression. Because we wanted to study the action of IDO-expressing dendritic cells (DCs) on allogeneic T cells, the human IDO gene was inserted into an adenoviral vector and expressed in DCs. Transgenic DCs decreased the concentration of tryptophan, increased the concentration of kynurenine, the main tryptophan metabolite, and suppressed allogeneic T cell proliferation in vitro. Kynurenine, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid, but no other IDO-induced tryptophan metabolites, suppressed the T cell response, the suppressive effects being additive. T cells, once stopped in their proliferation, could not be restimulated. Inhibition of proliferation was likely due to T cell death because suppressive tryptophan catabolites exerted a cytotoxic action on CD3+ cells. This action preferentially affected activated T cells and increased gradually with exposure time. In addition to T cells, B and natural killer (NK) cells were also killed, whereas DCs were not affected. Our findings shed light on suppressive mechanisms mediated by DCs and provide an explanation for important biological processes in which IDO activity apparently is increased, such as protection of the fetus from rejection during pregnancy and possibly T cell death in HIV-infected patients

The Role of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 in the p38/TNF-α Pathway of Systemic and Cutaneous Inflammation

Mitogen-activated protein kinase-activated protein kinase 2 (MK2) is a downstream molecule of p38, involved in the production of TNF-α, a key cytokine, and an established drug target for many inflammatory diseases. We investigated the role of MK2 in skin inflammation to determine its drug target potential. MK2 deficiency significantly decreased plasma TNF-α levels after systemic endotoxin application. Deficient mice showed decreased skin edema formation in chronic 2-O-tetradecanoylphorbol-13-acetate (TPA)-induced irritative dermatitis and in subacute 2,4-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity. Surprisingly, MK2 deficiency did not inhibit edema formation in subacute 2,4-dinitrochlorobenzene (DNCB)-induced contact allergy and even increased TNF-α and IL-1β levels as well as granulocyte infiltration in diseased ears. Ear inflammation in this model, however, was inhibited by TNF-α neutralization as it was in the subacute DNFB model. MK2 deficiency also did not show anti-inflammatory effects in acute DNFB-induced contact hypersensitivity, whereas the p38 inhibitor, SB203580, ameliorated skin inflammation supporting a pathophysiological role of p38. When evaluating possible mechanisms, we found that TNF-α production in MK2-deficient spleen cells was strongly diminished after TLR stimulation but less affected after T-cell receptor stimulation. Our data suggest that MK2, in contrast to its downstream effector molecule, TNF-α, has a rather elusive role in T-cell-dependent cutaneous inflammation

Role of undecaprenyl phosphokinase in mycobacteria

Die Familie der Mykobakterien setzt sich aus pathogenen und apathogenen Vertretern zusammen. In dieser Arbeit wurden 3 Mitglieder dieser Familie für Untersuchungen herangezogen: ihr prominentester pathogener Vertreter Mycobacterium tuberculosis, der Erreger der Tuberkulose, das als Impfstoff eingesetzte Mycobacterium bovis BCG, das durch Attenuierung aus dem Rindertuberkulose-Erreger Mycobacterium bovis hervorging und das apathogene Bodenbakterium Mycobacterium smegmatis. Ein Schlüssel zum Verständnis der Mykobakterien und speziell ihrer Widerstandsfähigkeit ist die Kenntnis ihrer komplexen Zellwand. Peptidoglycan als deren Bestandteil und insbesondere der mittels Undecaprenyl-Monophosphat bewerkstelligte Transport von Peptidoglycan-Vorläufern aus dem Cytoplasma an die Zelloberfläche steht dabei im Zentrum der Zellwandbildung. In M. tuberculosis, M. bovis BCG und M. smegmatis wurden Deletionsmutanten für die Undecaprenyl-Phosphokinase (Upk) hergestellt. Für M. smegmatis wurde gezeigt, daß die delta upk Deletionsmutante, in Übereinstimmung mit Deletionsmutanten homologer Gene in anderen Bakterien, eine erhöhte Sensitivität gegenüber dem die Zellwandsynthese hemmenden Antibiotikum Bacitracin aufwies. Überraschenderweise zeigte M. tuberculosis delta upk diesen Phänotyp nicht. Weiterhin ließ sich für M. smegmatis delta upk im Vergleich zum M. smegmatis Wildtyp Peptidoglycan an der Zelloberfläche in geringerem Maße nachweisen. Eindrucksvoll zeigte sich die Bedeutung der Undecaprenyl Phosphokinase in der gestörten Entwicklung von Biofilmen im Falle der M. smegmatis delta upk Mutante. Dies galt sowohl für in vitro Bedingungen als auch für ein, im Rahmen dieser Arbeit, neu entwickeltes in vivo Modell. Vergleiche von M. tuberculosis Wildtyp und M. tuberculosis Mutante auf der Ebene von Proteom- und Transkriptom-Analysen führten zur Identifikation eines zum mykobakteriellen Fettsäure-Synthese II (FASII) System gehörenden Operons, das im Falle der upk-Deletion verstärkt exprimiert wurde und damit möglicherweise einen Kompensationsmechanismus für die fehlende Phosphokinase darstellt. Eine reduzierte Persistenz von M. smegmatis delta upk in infizierten Makrophagen legte nahe, daß Upk bei mykobakteriellen Infektionen eine entscheidende Rolle für das Überleben der Bakterien und ihre Virulenz spielt. Dies konnte erstmals für M. tuberculosis im Rahmen von Maus-Infektionsversuchen gezeigt werden. M. tuberculosis delta upk ließ sich als neues Mitglied in eine Reihe von als growth in vivo (giv) klassifizierten Mutanten einreihen. Die Herstellung von Deletionsmutanten wird als Möglichkeit betrachtet, verbesserte Impfstoffe herzustellen. Die physiologische Konsequenz der Deletion sollte bestenfalls neben einer Attenuierung des Ausgangsbakteriums (gilt besonders für M. tuberculosis) eine Überexpression protektionsrelevanter Antigene zur Folge haben. Im Vergleich zum bestehenden Impfstoff M. bovis BCG führte die Impfung von Mäusen mit M. bovis BCG delta upk sowohl zu geringerer bakterieller im Anschluß an die Vakzinierung als auch zu einer verbesserten Langzeit-Protektion gegen Tuberkulose.The family of mycobacteria is composed of pathogenic and apathogenic bacteria. This study was performed with 3 members of this family, the most prominent pathogenic member, Mycobacterium tuberculosis, the causative agent of tuberculosis, the vaccine strain Mycobacterium bovis BCG which was developed by attenuation of the bovine tuberculosis agent Mycobacterium bovis, and Mycobacterium smegmatis which is apathogenic and widely distributed in soil. A key to understanding mycobacteria and, especially, their resistance is to understand the complexity of their cell wall. Peptidoglycan is a major component of the cell wall and the transport of peptidoglycan precursors out of the cytoplasm to the bacterial surface by undecaprenyl monophosphate is central to cell wall synthesis. Therefore, deletion mutants of the undecaprenyl phosphokinase gene (upk) were generated in M. tuberculosis, M. bovis BCG, and M. smegmatis. In the case of M. smegmatis it was shown that a delta upk deletion mutant, as with deletion mutants of homologous genes in other bacteria, exhibited an increased sensitivity to the antibiotic bacitracin, indicating that cell wall synthesis was hampered. Surprisingly, M. tuberculosis delta upk did not exhibit this phenotype. Furthermore, a lower level of peptidoglycan was detected on the cell surface of an M. smegmatis delta upk mutant compared to M. smegmatis wildtype. Relevance of the undecaprenyl phosphokinase was demonstrated by impaired biofilm development in the case of the M. smegmatis delta upk mutant. This was observed in vitro as well as in vivo using an animal model which was newly developed in this thesis. A fatty acid synthase II (FASII) system related operon revealed by comparative proteome- and transcriptome-analyses comparing M. tuberculosis wildtype and M. tuberculosis delta upk mutant, and may reflect a compensatory mechanism for the loss of upk. Reduced persistence of M. smegmatis in infected macrophages suggested a decisive role of Upk in mycobacterial infection concerning survival and virulence of bacteria. This was later demonstrated to be true for M. tuberculosis in a mouse model. M. tuberculosis delta upk was, therefore, classified as a new member of the group of growth in vivo (giv) mutants. Construction of deletion mutants is a strategy to identify improved vaccines. Ideally, the physiologic consequences of a gene deletion would result in attenuation of the modified bacterium (especially in the case of M. tuberculosis) and overexpression of antigens relevant for protection. Compared to the existing vaccine M. bovis BCG, vaccination of mice with M. bovis BCG delta upk exhibited a lower bacterial load upon vaccination as well as an improved long-lasting protection against M. tuberculosis infection

A drop in endogenous progesterone levels induces overt, extravaginally visible bleeding.

<p><b>A:</b> Experimental setup: Female mice were mated with vasectomized male mice (day 0). Pseudopregnant female mice were identified by vaginal plugs the next day. On day 4, endometrial decidualization was triggered by intra-uterine injection of sesame oil. The bleeding was monitored visually (detection of extravaginal blood) and microscopically (in H&E stained vaginal lavage fluid) from day 6 until necropsy. <b>B:</b> Systemic progesterone concentrations (mean) were determined by ELISA in sera from mice treated according to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032922#pone-0032922-g002" target="_blank">Figure 2A</a>. The Figure shows pooled data from two independent experiments (N≥10). <b>C:</b> Representative photograph of a mouse bleeding visibly extravaginally 4 days after decidualization on day 8 of pseudopregnancy. <b>D:</b> Visual determination of bleeding intensity of pseudopregnant mice with decidualized endometrium over 3 days from day 7 to day 9 (N = 16). <b>E:</b> Bleeding intensity (H&E bleeding scores; left axis) and pattern of serum progesterone levels (right axis) over time (open square = result for one individual mouse; filled squares = mean score for all mice in the group; N≥7; red = H&E bleeding score; gray = progesterone concentration). Data were collected in a single experiment. <b>F:</b> Bleeding scores of mifepristone-treated, pseudopregnant mice from day 7 to day 9 (treatment started on the evening of day 6; 10 mg/kg sc; open/filled squares see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032922#pone-0032922-g002" target="_blank">Figure 2E</a>; N = 7). The unpaired two-tailed Student's test was used for statistical analysis of the progesterone data (B, E), the two-tailed Mann-Whitney test for the ordinal H&E scores (*p≤0.05, **p≤0.01, ***p≤0.001).</p

Bleeding pattern and uterine weight mirror changes such as tissue construction, breakdown, and repair.

<p>Pseudopregnant BALB/c mice were treated according to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032922#pone-0032922-g002" target="_blank">Figure 2A</a> and sacrificed before (day 4) or after decidualization (days 6, 7, 8, 9, 10, 12). <b>A:</b> Macroscopic analysis of uteri at indicated points in time. <b>B:</b> Microscopic analysis of H&E-stained uteri (S, stromal cells; E, epithelium; L, lumen; B, extravasated blood). <b>C:</b> Analysis of uterus weights (left axis; open square = individual data; bar = mean) and bleeding intensity determined by H&E scores according to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032922#pone-0032922-g001" target="_blank">Figure 1</a> (right axis; filled square and bar analogous to the preceding; N≥7). The two-tailed Spearman test indicates a significant correlation (p = 0.0167, Spearman r = 0.9429) between increased uterus weight and H&E score. Data were assigned to the respective time (day 4 to day 12) and to the dominant processes at that time (construction - blue, breakdown - red, repair - green).</p

Regulation of different cellular processes in the endometrium is time point-specific.

<p>Endometrial mRNA levels of the indicated genes were determined by quantitative real-time PCR. All values were normalized to HPRT mRNA levels. Boxplots summarize the results of 5 to 9 mice per group (unpaired two-tailed Student's t-test, *p≤0.05, **p≤0.01, ***p≤0.001).</p