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During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery.sup.1-5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease. An analysis of 2,173 individuals from the MetaCardis cohort quantifies the individual and combinatorial effects of a range of drugs on host health, metabolome and gut microbiome in cardiometabolic disease., Author(s): Sofia K. Forslund [sup.1] [sup.2] [sup.3] [sup.4] [sup.5] [sup.6] , Rima Chakaroun [sup.7] , Maria Zimmermann-Kogadeeva [sup.1] , Lajos Markó [sup.2] [sup.4] [sup.5] , Judith Aron-Wisnewsky [sup.8] [sup.9] , [...]

Although the impact of Th17 cells on autoimmunity Is undisputable, their pathogenic effector mechanism Is still enigmatic. We discovered soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) complex proteins in Th17 cells that enable a vesicular glutamate release pathway that induces local intracytoplasmic calcium release and subsequent damage in neurons. This pathway is glutamine dependent and triggered by binding of [beta]1-integrin to vascular cell adhesion molecule 1 (VCAM-1) on neurons in the inflammatory context. Glutamate secretion could be blocked by inhibiting either glutaminase or [K.sub.V]1.3 channels, which are known to be linked to integrin expression and highly expressed on stimulated T cells. Although [K.sub.V]1.3 is not expressed in CNS tissue, intrathecal administration of a [K.sub.V]1.3 channel blocker or a glutaminase inhibitor ameliorated disability in experimental neuroinflammation. In humans, T cells from patients with multiple sclerosis secreted higher levels of glutamate, and cerebrospinal fluid glutamine levels were increased. Altogether, our findings demonstrate that [beta]1-integrin-and [K.sub.V]1.3 channel-dependent signaling stimulates glutamate release from Th17 cells upon direct cell-cell contact between Th17 cells and neurons., Introduction Glutamate is an essential excitatory neurotransmitter in the CNS, but excessive glutamate concentrations can be harmful, inducing excitotoxicity and massive loss of brain function (1-3). It has been suggested [...]

Apostle of Union: A Political Biography of Edward Everett. By Matthew Mason. (Chapel Hill, NC: University of North Carolina Press, 2016. Pp. xi, 434. $39.50.) If Edward Everett is remembered [...]

The study aims on the deactivation phenomena of two differently supported ruthenium catalysts during the oxidation of CO. The study concluded that a partial deactivation was observed initially, which was identified as an activated process, both under net reducing and net oxidizing conditions.

Asset management strategies are amongst the most important tools to address the economical, reliability, and operational requirements of extensive distribution networks in the environment of increasing deregulation. The key objectives are full utilization (i.e., exploitation of available network reserves), investment for expansion, and maintenance including asset replacement. The paper will focus on the methodology and the results of a condition-based preventive maintenance concept as part of the overall asset management strategy. As an example, the condition of 20-kV XLPE service aged cables of a German distribution grid is evaluated and categorized. The 'isothermal relaxation current analysis' (IRC-Analysis), which is a nondestructive and nonpartial discharge diagnostic method, is used to assess the cable conditions. Obtained categories are combined with the impact of one distinct cable on local system reliability in order to optimize replacement strategy. This concept called 'reliability centered maintenance' is applied by the author's company Lechwerke AG (LEW AG). As a result, the annual budget to guarantee service quality could be reduced substantially. Index Terms--Asset management strategy, condition-based maintenance, depolarization current, deregulation, isothermal relaxation current, nonpartial discharge diagnostic, reliability centered maintenance, XLPE distribution system.

The laser-gas interaction and the discharge initiation mechanism are presented. Resonant CO2 laser heating of low-pressure ammonia gas was applied to initiate 50 cm long, free-standing discharge channels.

There is indirect evidence from previous research that several executive disturbances in obsessive-compulsive disorder (OCD) are mediated by comorbid depressive symptoms. For the present study, the authors investigated whether OCD patients with elevated Hamilton Rating Scale for Depression (HRSD; M. Hamilton, 1967) scores would exhibit deficits in tasks sensitive to the medial and dorsolateral frontal cortex as well as other executive tasks. The 36 OCD patients were split along the median according to their HRSD scores and compared with matched control subjects. Patients with high HRSD scores performed significantly worse than control subjects and patients with low HRSD scores on the Wisconsin Card Sorting Test (J. Loong, 1990), the Trail-Making Test (TMT, Part B; R. M. Reitan, 1992), and the TMT difference score. Moreover, patients with high HRSD scores exhibited deficits on a (creative) verbal fluency task. It is suggested that comorbid depressive symptoms may have artificially inflated some executive deficit scores in previous studies.

Dwight D. Eisenhower decided to not openly confront Sen Joseph R. McCarthy over his investigations of 'communists in government.' Eisenhower might have splintered the Republican Party had he done so, although some analysts maintain hundreds of loyal government employees were unnecessarily driven from their positions.

Byline: R. Krausse (1), L. Garten (1), T. Harder (1), U. Ullmann (1), T. Birkner (2), M. Doniec (2), H. Grimm (2) Keywords: Key WordsHelicobacter pylori; CagA status; Clinical relevance; Immunofluorescence; PCR; Western blot Abstract: Background: The cagA (cytotoxin-associated gene A) protein is found in about 50% of Helicobacter pylori strains its clinical relevance in gastroduodenal disease is uncertain. Patients and Methods: The frequency of IgG antibodies to cagA was studied by using a commercial Western blot assay in sera of 189 patients with endoscopically and histologically confirmed gastroduodenal disease. In addition, 38 H. pylori strains isolated from biopsies were analyzed by immunofluorescence test (IFT) and PCR for detection of cagA protein and cagA gene sequences, respectively. Results: 54.3--60.0% of all patients with gastrointestinal diseases (chronic gastritis, gastric or duodenal ulcer and chronic duodenitis) and 28.6% with a normal mucosa were found to be positive for anti-cagA IgG antibodies. There was no significant difference in anti-cagA IgG seroprevalence between the different clinical entities. CagA-positive (cagA.sup.+) H. pylori strains were detected in 44.7% and 50% of the 38 isolates by PCR and IFT, respectively. 22 of 23 patients infected with cagA.sup.+ strains had anti-cagA antibodies. Using PCR as a gold standard, the sensitivity and specificity of the cagA IgG Western blot were 100.0% and 35.0%, respectively the sensitivity and specificity of the cagA IFT were 76.5% and 71.4%, respectively. The incidence of the cagA.sup.+ H. pylori strains detected either by PCR or IFT was significantly higher (p &lt 0.05 and p &lt 0.01, respectively) in patients with chronic duodenitis, gastric or duodenal ulcer compared to patients with chronic gastritis (66.7%, 80% and 30.4%, respectively). Conclusion: In this study the cagA-specific serological status in H. pylori infections as diagnosed by IgG Western blot was of no predictive value for severity of disease. In contrast, the cagA status of H. pylori isolates, diagnosed by IFT or PCR, was a predictive marker for severe disease and, therefore, also of clinical relevance in the assessment of the virulence of the infecting strain. Author Affiliation: (1) Institute of Medical Microbiology and Virology University of Kiel, Brunswiker Str. 4, D-24105 Kiel, Germany Phone: (+49/431)597-3298, Fax: -3296, e-mail: r.krausse@medmicrobio.uni-kiel.de, DE (2) Dept. of Surgery, University of Kiel, Arnold-Heller Str. 7, D-24105 Kiel, Germany Phone: (+49/431) 597-4581, Fax: -4327, DE Article note: Received: July 21, 2000 * Revision accepted: March 2, 2001

The design of a superconducting magnetic energy storage system (SMES) undertaken for the construction of a SMES facility at the Institute of Technology in Munich, Germany. The study demonstrated the need to configure the system's magnets as a toroidal coil for low induction and high current operation. Such a design was proven, via numerical field calculations, to result in an SMES with low energy density and minimal ac losses.

The Technische Universitat Munchen is working on the construction of a superconducting energy storage facility for experimental tests. Intended to be a key component of the test center is a 1.4 MJ superconducting magnetic energy storage system that consists of six sc coils. Configured as a torus, the coils will be cooled by supercritical helium. It is expected to facilitate studies in load noise leveling and load balancing three-phase power system.

Knowing the thermodynamic stability of transition metal oxide nanoparticles is important for understanding and controlling their role in a variety of industrial and environmental systems. Using calorimetric data on surface energies for cobalt, iron, manganese, and nickel oxide systems, we show that surface energy strongly influences their redox equilibria and phase stability. Spinels ([M.sub.3][O.sub.4]) commonly have tower surface energies than metals (M), rocksalt oxides (MO), and trivalent oxides ([M.sub.2][O.sub.3]) of the same metal; thus, the contraction of the stability field of the divalent oxide and expansion of the spinel field appear to be general phenomena. Using tabulated thermodynamic data for bulk phases to calculate redox phase equilibria at the nanoscale can lead to errors of several orders of magnitude in oxygen fugacity and of 100 to 200 kelvin in temperature. 10.1126/science.1195875