Multi-asset scenario building for trend-following trading strategies

This paper presents a new method for improving the performance of trend-following trading strategies. This new approach improves the inherent problem of trend-following strategies, which is their lagging signals. We simulate alternative price paths of financial assets using a modification of a distribution-free, semi-parametric approach that combines a GARCH-type process with historical simulation. These simulated price paths are used to construct and optimize trend-following trading strategies. The study is conducted in a multi-asset environment. Our empirical results demonstrate the superior performance for multiple assets on a large set of performance metrics compared to widely applied trend-following trading strategies. The results are robust to variations in input specifications, such as tested time and lookback period, number of simulated price paths, and price steps per simulation, but also in terms of trading strategy calibration and market positioning (long-only, long–short, short-only)

Antimicrobial susceptibility patterns of blood culture isolates from foals in Switzerland.

INTRODUCTION We report blood culture results of 43 foals admitted to an equine hospital for medical or surgical disorders and determine minimal inhibitory concentrations (MIC) of different antibiotics. Eleven foals had a positive blood culture result despite prior administration of antibiotics in 10 of these animals. MIC values above EUCAST and/or CLSI breakpoints were identified in coagulase-negative staphylococci, methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium. Gram-negative isolates were less frequently identified and did not appear to exhibit increased MIC values. This study shows that bloodstream infections in foals in Switzerland are caused by diverse bacteria including Gram-positive bacteria which exhibit resistance to several classes of antibiotics

Corynebacterium uberis sp. nov. frequently isolated from bovine mastitis.

Several strains belonging to the genus Corynebacterium, but not to any described species of the genus were isolated from bovine mastitic milk samples over the past five years in the diagnostic unit of the University of Bern. Six of these strains (18M0132T, 17M2518, 18M0913, 19M0083, 20M1046 and 20M1090) that were phenotypically similar were further characterized genotypically. Gram-positive coryneform rods were catalase positive, facultative anaerobe and CAMP-test negative. Whole genome sequencing and subsequent phylogenetic analysis revealed their genome size to be 2.53 Mb and their G + C content to be between 65.4 and 65.5 mol%. Digital DNA-DNA hybridisation (dDDH) showed the highest similarity of only less than 20% with Corynebacterium mastitidis and Corynebacterium frankenforstense, which indicated that the isolates belong to an undescribed Corynebacterium species. This was confirmed by studying the average nucleotide identity (ANI) where the accepted species boundary is around 95% and which ranged between 70.3% and 74.9% with the most closely related species C. mastitidis. We established MALDI-TOF fingerprints of the species, which allows a clear separation from related species and can be used by other laboratories for diagnostic purposes. Based on our analyses we conclude that the selected strains belong to a previously undescribed species and propose the name Corynebacterium uberis sp. nov. The proposed type strain is 18M0132T (=DSM 111922T, = CCOS 1972T)

IS711-based real-time PCR assay as a tool for detection of Brucella spp. in wild boars and comparison with bacterial isolation and serology

<p>Abstract</p> <p>Background</p> <p>Control of brucellosis in livestock, wildlife and humans depends on the reliability of the methods used for detection and identification of bacteria. In the present study, we describe the evaluation of the recently established real-time PCR assay based on the <it>Brucella</it>-specific insertion sequence IS<it>711 </it>with blood samples from 199 wild boars (first group of animals) and tissue samples from 53 wild boars (second group of animals) collected in Switzerland. Results from IS<it>711 </it>real-time PCR were compared to those obtained by bacterial isolation, Rose Bengal Test (RBT), competitive ELISA (c-ELISA) and indirect ELISA (i-ELISA).</p> <p>Results</p> <p>In the first group of animals, IS<it>711 </it>real-time PCR detected infection in 11.1% (16/144) of wild boars that were serologically negative. Serological tests showed different sensitivities [RBT 15.6%, c-ELISA 7.5% and i-ELISA 5.5%] and only 2% of blood samples were positive with all three tests, which makes interpretation of the serological results very difficult. Regarding the second group of animals, the IS<it>711 </it>real-time PCR detected infection in 26% of animals, while <it>Brucella </it>spp. could be isolated from tissues of only 9.4% of the animals.</p> <p>Conclusion</p> <p>The results presented here indicate that IS<it>711 </it>real-time PCR assay is a specific and sensitive tool for detection of <it>Brucella </it>spp. infections in wild boars. For this reason, we propose the employment of IS<it>711 </it>real-time PCR as a complementary tool in brucellosis screening programs and for confirmation of diagnosis in doubtful cases.</p

Conversion of Anergic T Cells Into Foxp3−^- IL-10+^+ Regulatory T Cells by a Second Antigen Stimulus In Vivo

T cell anergy is a common mechanism of T cell tolerance. However, although anergic T cells are retained for longer time periods in their hosts, they remain functionally passive. Here, we describe the induction of anergic CD4$^+$ T cells in vivo by intravenous application of high doses of antigen and their subsequent conversion into suppressive Foxp3$^-$ IL-10$^+$ Tr1 cells but not Foxp3$^+$ Tregs. We describe the kinetics of up-regulation of several memory-, anergy- and suppression-related markers such as CD44, CD73, FR4, CD25, CD28, PD-1, Egr-2, Foxp3 and CTLA-4 in this process. The conversion into suppressive Tr1 cells correlates with the transient intracellular CTLA-4 expression and required the restimulation of anergic cells in a short-term time window. Restimulation after longer time periods, when CTLA-4 is down-regulated again retains the anergic state but does not lead to the induction of suppressor function. Our data require further functional investigations but at this stage may suggest a role for anergic T cells as a circulating pool of passive cells that may be re-activated into Tr1 cells upon short-term restimulation with high and systemic doses of antigen. It is tentative to speculate that such a scenario may represent cases of allergen responses in non-allergic individuals

Ballistic and molecular dynamics simulations of aluminum deposition in micro-trenches

Two different feature scale modeling frameworks are utilized for the study of aluminum (Al) deposition profiles inside micro-trenches. The first framework, which is applied in metal-organic chemical vapor deposition (MOCVD) of Al, couples a ballistic model for the local flux calculation, a surface chemistry model, and a profile evolution algorithm. The calculated conformity of the deposited film is compared with experimental results corresponding to Al MOCVD from dimethylethylamine alane (DMEAA). The outcome of the comparison is that the effective sticking coefficient of DMEAA is in the range of 0.1 - 1. There is also a strong indication that surface reaction kinetics follows Langmuir - Hinshelwood or Eley - Rideal mechanism. The second framework, which is applied in physical vapor deposition of Al, implements 2D molecular dynamics (MD) simulations. The simulations are performed in a "miniaturized" domain of some hundreds of Angstroms and are used to explore micro-trench filling during magnetron sputtering deposition of Al on a rotated substrate. Most of the experimental results are qualitatively reproduced by the MD simulations; the rotation, aspect ratio, and kinetic energy effects are correctly described despite the completely different length scales of simulation and experiment. The sticking probability of Al is calculated 0.6 for the conditions of the experiments

Structure-Activity Relationship and Mode-Of-Action Studies Highlight 1-(4-Biphenylylmethyl)-1H-imidazole-Derived Small Molecules as Potent CYP121 Inhibitors

CYP121 of Mycobacterium tuberculosis (Mtb) is an essential target for the development of novel potent drugs against tuberculosis (TB). Besides known antifungal azoles, further compounds of the azole class were recently identified as CYP121 inhibitors with antimycobacterial activity. Herein, we report the screening of a similarity-oriented library based on the former hit compound, the evaluation of affinity toward CYP121, and activity against M. bovis BCG. The results enabled a comprehensive SAR study, which was extended through the synthesis of promising compounds and led to the identification of favorable features for affinity and/or activity and hit compounds with 2.7-fold improved potency. Mode of action studies show that the hit compounds inhibit substrate conversion and highlighted CYP121 as the main antimycobacterial target of our compounds. Exemplified complex crystal structures of CYP121 with three inhibitors reveal a common binding site. Engaging in both hydrophobic interactions as well as hydrogen bonding to the sixth iron ligand, our compounds block a solvent channel leading to the active site heme. Additionally, we report the first CYP inhibitors that are able to reduce the intracellular replication of M. bovis BCG in macrophages, emphasizing their potential as future drug candidates against TB.Fil: Walter, Isabell. Helmholtz Institute for Pharmaceutical Research Saarland; AlemaniaFil: Adam, Sebastian. Universitat Saarland; AlemaniaFil: Gentilini, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina. Twincore; AlemaniaFil: Kany, Andreas M.. Helmholtz Institute for Pharmaceutical Research Saarland; AlemaniaFil: Brengel, Christian. Helmholtz Institute for Pharmaceutical Research Saarland; AlemaniaFil: Thomann, Andreas. Helmholtz Institute for Pharmaceutical Research Saarland; AlemaniaFil: Sparwasser, Tim. Twincore; AlemaniaFil: Köhnke, Jesko. Universitat Saarland; AlemaniaFil: Hartmann, Rolf W.. Universitat Saarland; Alemania. Helmholtz Institute for Pharmaceutical Research Saarland; Alemani

Actinomycosis in a gray four-eyed opossum (Philander opossum) caused by a novel species of Schaalia

Background: Infective lesions of the jaws and adjacent tissues (lumpy jaw disease, LJD) have been recognized as one major cause of death of captive macropods. Fusobacterium necrophorum and Actinomyces species serve as the main source of LJD in kangaroos and wallabies. Currently, little is reported about LJD or similar diseases in opossums. Case presentation: Here we report a case of actinomycosis resembling the entity lumpy jaw disease in a gray four-eyed opossum, caused by a novel species of Schaalia. A 2.8 year old male Philander opossum was presented with unilateral swelling of the right mandible. After an initial treatment with marbofloxacin, the opossum was found dead the following day and the carcass was submitted for necropsy. Postmortem examination revealed severe mandibular skin and underlying soft tissue infection with subsequent septicemia as the cause of death. Histological examination demonstrated Splendore-Hoeppli phenomenon, typically seen in classical cases of actinomycosis. Bacteriology of liver and mandibular mass yielded a previously undescribed species of Schaalia, whose 16 S rRNA gene sequence was 97.0 % identical to Schaalia canis. Whole genome sequencing of the opossum isolate and calculation of average nucleotide identity confirmed a novel species of Schaalia, for which no whole genome sequence is yet available. Conclusions: The herewith reported Schaalia infection in the gray four-eyed opossum resembling classical actinomycosis gives a novel insight into new exotic animal bacterial diseases. Schaalia species may belong to the normal oral microbiome, as in macropods, and may serve as a contributor to opportunistic infections. Due to the lack of current literature, more insights and improved knowledge about Schaalia spp. and their pathogenicity will be useful to choose appropriate therapy regimens and improve the treatment success rate and outcome in exotic and endangered species

Die LUCA Office Simulation in der Lehrerinnen- und Lehrerbildung - didaktische Design-Empfehlungen und erforderliche Lehrkompetenzen

Vor dem Hintergrund einer u. a. durch die Digitalisierung bedingten Verschiebung von Kompetenzanforderungen an Lernende bei gleichzeitig wachsenden digitalen Möglichkeiten an beruflichen Schulen muss nicht nur von einer neuen digitalen Rea- lität beruflicher Lernprozesse, sondern auch von einer neuen Realität beruflicher Lehrprozesse ausgegangen werden. Wie ein digital gestützter Unterricht für die kauf- männische Bildung aussehen kann und welche professionellen Kompetenzen von Lehrkräften hierfür relevant sein könnten, wird am Beispiel der an der Universität Mannheim entwickelten Bürosimulation LUCA1 erörtert. Der Beitrag geht konzeptio- nell-induktiv anhand der LUCA-Funktionen eines konkreten Anwendungsbeispiels sowie Modellen digitaler Lehrkompetenzen der Frage nach, welche Unterrichtskom- petenzen diesbezüglich bei Lehrkräften erforderlich sind. Im Ergebnis werden spezi- fische Aspekte digitaler Unterrichtskompetenz identifiziert, die für die Anwendung virtueller Lernsimulationen, wie der LUCA-Bürosimulation, hilfreich sind

First Staphylococcal Cassette Chromosome mec Containing a mecB-Carrying Gene Complex Independent of Transposon Tn6045 in a Macrococcus caseolyticus Isolate from a Canine Infection.

A methicillin-resistant mecB-positive Macrococcus caseolyticus (strain KM45013) was isolated from the nares of a dog with rhinitis. It contained a novel 39-kb transposon-defective complete mecB-carrying staphylococcal cassette chromosome mec element (SCCmecKM45013). SCCmecKM45013 contained 49 coding sequences (CDSs), was integrated at the 3' end of the chromosomal orfX gene, and was delimited at both ends by imperfect direct repeats functioning as integration site sequences (ISSs). SCCmecKM45013 presented two discontinuous regions of homology (SCCmec coverage of 35%) to the chromosomal and transposon Tn6045-associated SCCmec-like element of M. caseolyticus JCSC7096: (i) the mec gene complex (98.8% identity) and (ii) the ccr-carrying segment (91.8% identity). The mec gene complex, located at the right junction of the cassette, also carried the β-lactamase gene blaZm (mecRm-mecIm-mecB-blaZm). SCCmecKM45013 contained two cassette chromosome recombinase genes, ccrAm2 and ccrBm2, which shared 94.3% and 96.6% DNA identity with those of the SCCmec-like element of JCSC7096 but shared less than 52% DNA identity with the staphylococcal ccrAB and ccrC genes. Three distinct extrachromosomal circularized elements (the entire SCCmecKM45013, ΨSCCmecKM45013 lacking the ccr genes, and SCCKM45013 lacking mecB) flanked by one ISS copy, as well as the chromosomal regions remaining after excision, were detected. An unconventional circularized structure carrying the mecB gene complex was associated with two extensive direct repeat regions, which enclosed two open reading frames (ORFs) (ORF46 and ORF51) flanking the chromosomal mecB-carrying gene complex. This study revealed M. caseolyticus as a potential disease-associated bacterium in dogs and also unveiled an SCCmec element carrying mecB not associated with Tn6045 in the genus Macrococcus