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The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p–Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
Principal findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci.
Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
Cytokine-induced killer (CIK) cells are an immunotherapeutic approach to combat relapse following allogeneic hematopoietic stem cell transplantation (HSCT) in acute leukemia or myelodysplastic syndrome (MDS) patients. Prompt and sequential administration of escalating cell doses improves the efficacy of CIK cell therapy without exacerbating graft vs. host disease (GVHD). This study addresses manufacturing-related issues and aimed to develop a time-, personal- and cost-saving good manufacturing process (GMP)-compliant protocol for the generation of ready-for-use therapeutic CIK cell doses starting from one unstimulated donor-derived peripheral blood (PB) or leukocytapheresis (LP) products. Culture medium with or without the addition of either AB serum, fresh frozen plasma (FFP) or platelet lysate (PL) was used for culture. Fresh and cryopreserved CIK cells were compared regarding expansion rate, viability, phenotype, and ability to inhibit leukemia growth. Cell numbers increased by a median factor of 10-fold in the presence of FFP, PL, or AB serum, whereas cultivation in FFP/PL-free or AB serum-free medium failed to promote adequate CIK cell proliferation (p < 0.01) needed to provide clinical doses of 1 × 106 T cells/kG, 5 × 106 T cells/kG, 1 × 107 T cells/kG, and 1 × 108 T cells/kG recipient body weight. CIK cells consisting of T cells, T- natural killer (T-NK) cells and a minor fraction of NK cells were not significantly modified by different medium supplements. Moreover, neither cytotoxic potential against leukemic THP-1 cells nor cell activation shown by CD25 expression were significantly influenced. Moreover, overnight and long-term cryopreservation had no significant effect on the composition of CIK cells, their phenotype or cytotoxic potential. A viability of almost 93% (range: 89–96) and 89.3% (range: 84–94) was obtained after freeze-thawing procedure and long-term storage, respectively, whereas viability was 96% (range: 90-97) in fresh CIK cells. Altogether, GMP-complaint CIK cell generation from an unstimulated donor-derived PB or LP products was feasible. Introducing FFP, which is easily accessible, into CIK cell cultures was time- and cost-saving without loss of viability and potency in a 10-12 day batch culture. The feasibility of cryopreservation enabled storage and delivery of sequential highly effective ready-for-use CIK cell doses and therefore reduced the number of manufacturing cycles.
Janthinobacteria commonly form biofilms on eukaryotic hosts and are known to synthesize antibacterial and antifungal compounds. Janthinobacterium sp. HH01 was recently isolated from an aquatic environment and its genome sequence was established. The genome consists of a single chromosome and reveals a size of 7.10 Mb, being the largest janthinobacterial genome so far known. Approximately 80% of the 5,980 coding sequences (CDSs) present in the HH01 genome could be assigned putative functions. The genome encodes a wealth of secretory functions and several large clusters for polyketide biosynthesis. HH01 also encodes a remarkable number of proteins involved in resistance to drugs or heavy metals. Interestingly, the genome of HH01 apparently lacks the N-acylhomoserine lactone (AHL)-dependent signaling system and the AI-2-dependent quorum sensing regulatory circuit. Instead it encodes a homologue of the Legionella- and Vibrio-like autoinducer (lqsA/cqsA) synthase gene which we designated jqsA. The jqsA gene is linked to a cognate sensor kinase (jqsS) which is flanked by the response regulator jqsR. Here we show that a jqsA deletion has strong impact on the violacein biosynthesis in Janthinobacterium sp. HH01 and that a jqsA deletion mutant can be functionally complemented with the V. cholerae cqsA and the L. pneumophila lqsA genes.
Balloon-borne measurements of CFC-11 (on flights of the DIRAC in situ gas chromatograph and the DESCARTES grab sampler), ClO and O3 were made during the 1999/2000 winter as part of the SOLVE-THESEO 2000 campaign. Here we present the CFC-11 data from nine flights and compare them first with data from other instruments which flew during the campaign and then with the vertical distributions calculated by the SLIMCAT 3-D CTM. We calculate ozone loss inside the Arctic vortex between late January and early March using the relation between CFC-11 and O3 measured on the flights, the peak ozone loss (1200 ppbv) occurs in the 440–470 K region in early March in reasonable agreement with other published empirical estimates. There is also a good agreement between ozone losses derived from three independent balloon tracer data sets used here. The magnitude and vertical distribution of the loss derived from the measurements is in good agreement with the loss calculated from SLIMCAT over Kiruna for the same days.
Ob zum Austausch von zwischenmenschlichen Bedürfnissen, wie dem Gedankengut oder zu Geschäftszwecken, wie am Beispiel der Lingua Franca, galt Sprache seit jeher als das Kommunikationsmittel der menschlichen Spezies. Durch den wachsenden Bedarf an Mehrsprachigkeit im 20. Jahrhundert, rückte die Spracherwerbsforschung zunehmend ins Forschungszentrum. Die Erforschung von Deutsch als Zweitsprache (L2) anhand verschiedenster Muttersprachen (L1s) findet ihre Anfänge Mitte der 1980er Jahre (vgl. MEISEL 1975). Bereits zu Beginn des 19. Jahrhunderts erkannten Forscher, wie SCHLEGEL (1818), die Wichtigkeit, Sprachen nach morphotypologischen Klassifikationen zu schematisieren, um geneologische Zusammenhänge zwischen Sprachen im Kontext analysieren zu können. Die Frage, wie und ob sprachliche Transferprozesse auf eine sprachtypologische (Nicht)-Verwandtschaft zwischen L1 und L2 zurückzuführen sind, ist Gegenstand dieser Studie. Die untersuchten L1s sind Spanisch (flektierend), Vietnamesisch (isolierend), Türkisch (agglutinierend) sowie Deutsch (flektierend) als L2. Praktisch werden Daten zu zwei Grammatikalitäten analysiert: die Subjekt-Verb-Kongruenz sowie die Realisierung der grammatischen Artikel im Deutschen. Die Ergebnisse zeigen, dass in beiden Bereichen eine enge Verbindung zwischen strukturellen Ähnlichkeiten sowie Differenzen für den Transfer zwischen L1 und L2 ausschlaggebend sein kann, da die spanischsprachigen TeilnehmerInnen die geringsten Interferenzquoten, die vietnamesischsprachigen TeilnehmerInnen hingegen die höchsten Fehlerquoten aufzeigen.
Balloon-borne measurements of CFC11 (from the DIRAC in situ gas chromatograph and the DESCARTES grab sampler), ClO and O3 were made during the 1999/2000 Arctic winter as part of the SOLVE-THESEO 2000 campaign, based in Kiruna (Sweden). Here we present the CFC11 data from nine flights and compare them first with data from other instruments which flew during the campaign and then with the vertical distributions calculated by the SLIMCAT 3D CTM. We calculate ozone loss inside the Arctic vortex between late January and early March using the relation between CFC11 and O3 measured on the flights. The peak ozone loss (~1200ppbv) occurs in the 440-470K region in early March in reasonable agreement with other published empirical estimates. There is also a good agreement between ozone losses derived from three balloon tracer data sets used here. The magnitude and vertical distribution of the loss derived from the measurements is in good agreement with the loss calculated from SLIMCAT over Kiruna for the same days.
Objective: Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving.
Methods: We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan–Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data.
Results: We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59–66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39–0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011–2017), being on a multi-tablet regimen (MTR).
Conclusions: Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.
Correction to: Infection (2020) 48:723–733 https://doi.org/10.1007/s15010-020-01469-6. The original version of this article unfortunately contained a mistake. In this article the authors Dirk Schürmann at affiliation Charité, University Medicine, Berlin, Olaf Degen at affiliation University Clinic Hamburg Eppendorf, Hamburg and Heinz-August Horst at affiliation University Hospital Schleswig–Holstein, Kiel, Germany were missing from the author list. The original article has been corrected.