A comparative time-resolved CW EPR and FT EPR investigation of the addition of 2-hydroxy-2-propyl radicals to acrylate and methacrylate monomers

The addition of 2-hydroxy-2-propyl radicals to n-butyl acrylate and n-butyl methacrylate has been investigated by time-resolved continuous wave electron paramagnetic resonance (TR CW EPR) and time-resolved Fourier transform electron paramagnetic resonance (TR FT EPR). The 2-hydroxy-2-propyl radicals were generated by the photolysis of acetone in propan-2-ol (through hydrogen abstraction) and by the photolysis of a ketone 5 (through α-cleavage). The TR CW and TR FT spectra were experimentally equivalent for the addition of 2-hydroxy-2-propyl radicals to n-butyl acrylate to produce 3a. However, there are distinct differences between the TR CW and TR FT spectra for the addition of 2-hydroxy-2-propyl radicals to n-butyl methacrylate which produces the radical adduct 4a. In particular, a number of hyperfine lines clearly present in the TR CW spectra are much weaker in, or are absent from, the TR FT spectra. The differences in the TR CW and TR FT spectra are attributed to hindered rotation, which is important in the spectrum of the adduct of 2-hydroxy-2-propyl radicals to n-butyl methacrylate (4a), but not in the spectrum of the adduct of 2-hydroxy-2-propyl radicals to n-butyl acrylate (3a). The hindered rotation is shown to selectively shorten the spin–spin relaxation time, T2, for certain hyperfine lines in the spectrum of 4a, resulting in broadening or disappearance of these lines and explaining the differences between the TR CW and TR FT spectra

Response Time Analysis for Sporadic Server based Budget Scheduling in Real Time Virtualization Environments

Virtualization techniques for embedded real-time systems typically employ TDMA scheduling to achieve temporal isolation among different virtualized applications. Recent work already introduced sporadic server based solutions relying on budgets instead of a fixed TDMA schedule. While providing better average-case response times for IRQs and tasks, a formal response time analysis for the worst-case is still missing. In order to confirm the advantage of a sporadic server based budget scheduling, this paper provides a worst-case response time analysis. To improve the sporadic server based budget scheduling even more, we provide a background scheduling implementation which will also be covered by the formal analysis. We show correctness of the analysis approach and compare it against TDMA based systems. In addition to that, we provide response time measurements from a working hypervisor implementation on an ARM based development board

Role of Alanine Racemase Mutations in Mycobacterium tuberculosis d-Cycloserine Resistance.

A screening of more than 1,500 drug-resistant strains of Mycobacterium tuberculosis revealed evolutionary patterns characteristic of positive selection for three alanine racemase (Alr) mutations. We investigated these mutations using molecular modeling, in vitro MIC testing, as well as direct measurements of enzymatic activity, which demonstrated that these mutations likely confer resistance to d-cycloserine

What Is Resistance? Impact of Phenotypic versus Molecular Drug Resistance Testing on Therapy for Multi- and Extensively Drug-Resistant Tuberculosis.

Rapid and accurate drug susceptibility testing (DST) is essential for the treatment of multi- and extensively drug-resistant tuberculosis (M/XDR-TB). We compared the utility of genotypic DST assays with phenotypic DST (pDST) using Bactec 960 MGIT or Löwenstein-Jensen to construct M/XDR-TB treatment regimens for a cohort of 25 consecutive M/XDR-TB patients and 15 possible anti-TB drugs. Genotypic DST results from Cepheid GeneXpert MTB/RIF (Xpert) and line probe assays (LPAs; Hain GenoType MTBDRplus 2.0 and MTBDRsl 2.0) and whole-genome sequencing (WGS) were translated into individual algorithm-derived treatment regimens for each patient. We further analyzed if discrepancies between the various methods were due to flaws in the genotypic or phenotypic test using MIC results. Compared with pDST, the average agreement in the number of drugs prescribed in genotypic regimens ranged from just 49% (95% confidence interval [CI], 39 to 59%) for Xpert and 63% (95% CI, 56 to 70%) for LPAs to 93% (95% CI, 88 to 98%) for WGS. Only the WGS regimens did not contain any drugs to which pDST showed resistance. Importantly, MIC testing revealed that pDST likely underestimated the true rate of resistance for key drugs (rifampin, levofloxacin, moxifloxacin, and kanamycin) because critical concentrations (CCs) were too high. WGS can be used to rule in resistance even in M/XDR strains with complex resistance patterns, but pDST for some drugs is still needed to confirm susceptibility and construct the final regimens. Some CCs for pDST need to be reexamined to avoid systematic false-susceptible results in low-level resistant isolates

MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era.

BACKGROUND: Multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains not detected by commercial molecular drug susceptibility testing (mDST) assays due to the RpoB I491F resistance mutation are threatening the control of MDR tuberculosis (MDR-TB) in Eswatini. METHODS: We investigate the evolution and spread of MDR strains in Eswatini with a focus on bedaquiline (BDQ) and clofazimine (CFZ) resistance using whole-genome sequencing in two collections ((1) national drug resistance survey, 2009-2010; (2) MDR strains from the Nhlangano region, 2014-2017). RESULTS: MDR strains in collection 1 had a high cluster rate (95%, 117/123 MDR strains) with 55% grouped into the two largest clusters (gCL3, n = 28; gCL10, n = 40). All gCL10 isolates, which likely emerged around 1993 (95% highest posterior density 1987-1998), carried the mutation RpoB I491F that is missed by commercial mDST assays. In addition, 21 (53%) gCL10 isolates shared a Rv0678 M146T mutation that correlated with elevated minimum inhibitory concentrations (MICs) to BDQ and CFZ compared to wild type isolates. gCL10 isolates with the Rv0678 M146T mutation were also detected in collection 2. CONCLUSION: The high clustering rate suggests that transmission has been driving the MDR-TB epidemic in Eswatini for three decades. The presence of MDR strains in Eswatini that are not detected by commercial mDST assays and have elevated MICs to BDQ and CFZ potentially jeopardizes the successful implementation of new MDR-TB treatment guidelines. Measures to limit the spread of these outbreak isolates need to be implemented urgently

Scheduling Mechanismen für effiziente und sichere Integration von Systemen im Automobilbereich

During the last years, the demand of computing power in modern cars has risen continuously, especially due to modern topics like assisted driving. In order to provide the required computing power, the chip manufactures focused in the past on the switch from single- to multicore CPU architectures. Such powerful multicore CPUs allow the integration of multiple software components on the same hardware, therefore reducing the overall number of ECUs inside a car. While multicore CPUs are well-known in general purpose computing, the efficient use in highly embedded systems with real-time requirements is more challenging. For the integration of multiple software components on the same hardware, freedom interference between those components must be enforced to ensure a safe execution. In case of existing legacy software the problem is often based on previously optimized execution for a singlecore CPU and as a result the parallel execution of such legacy software on multiple cores is not straight forward. This dissertation describes two possible scheduling techniques in order to enable sensible use of the new available computing power. The first mechanism uses partition based virtualization, which has been a well-known technique in avionics with ARINC653. Objective is the integration of multiple software components on the same ECU. Freedom from interference is achieved through the execution on top of a hypervisor, implementing and monitoring the partition based virtualization. Second, an integration of the LET paradigm into an automotive system architecture, enabling a lock-less synchronized communication across core boundaries. In general, such a mechanism allows a synchronization of software among multiple CPU cores. This allows synchronization across core boundaries which can be used for both, existing legacy software as well as virtualized partitions. The scientific contribution of this dissertation is primarily the integration of both mechanisms into an automotive context. This includes a response time analysis as well as a discussion of certain implementation challenges. Both mechanisms will be evaluated in a prototype implementation, including a discussion of the results.Auf Grund moderner Themen wie dem assistierten Fahren steigt der Bedarf an Rechenleistung in aktuellen Fahrzeugen seit einigen Jahren kontinuierlich an. Um die erforderliche Rechenleistung zur Verfügung zu stellen, konzentrierten sich die Prozessorhersteller in der Vergangenheit auf den Wechsel von Einzel- zu Mehrkern-CPU Architekturen. Durch die zusätzliche Leistung ermöglichen solche Mehrkern-CPUs die Integration von zuvor einzeln ausgeführten Softwarekomponenten auf derselben Hardware, was zu einer Reduktion der Gesamtzahl an ECUs in Fahrzeugen beiträgt. Während Mehrkern-CPUs in Standard Computersystemen bereits seit langem Verwendung finden, ist der effiziente Einsatz in eingebetteten Systemen mit Echtzeitanforderungen häufig schwierig. Für die Integration von mehreren Softwarekomponenten auf derselben Hardware muss die Störungsfreiheit zwischen den einzelnen Komponenten für eine sichere Ausführung gewährleistet sein. Ein weiteres Problem besteht häufig bei bereits existierender Legacy-Software, welche für die Ausführung auf einer einzelnen CPU während der Entwicklung optimiert wurde und daher nicht ohne weiteres auf mehrere Prozessorkerne verteilt werden kann. Diese Dissertation beschreibt zwei Mechanismen, welche eine sinnvolle Nutzung der zusätzlichen Rechenleistung ermöglichen sollen. Der erste Mechanismus verwendet partitionsbasierter Virtualisierung, welche in der Avionik bereits in der Vergangenheit in Form von ARINC653 Verwendung gefunden hat. Ziel ist hierbei, mehrere Softwarekomponenten auf derselben ECU zu integrieren. Die Störungsfreiheit wird durch die Ausführung über einen Hypervisor erreicht, welcher die partitionsbasierte Virtualisierung implementiert und überwacht.Zweitens wird die Integration des LET Paradigmas in eine automobile Systemarchitektur gezeigt, welches eine blockierungsfeie Synchronisation der Kommunikation über Kerngrenzen hinweg ermöglicht. Generell erlaubt dieser Mechanismus eine Synchronisation von Software über mehrere Prozessorkerne hinweg, was sowohl für die parallele Ausführung von Legacy-Software als auch von virtualisierten Partitionen genutzt werden kann. Der wissenschaftliche Beitrag dieser Dissertation ist in erster Linie die Integration beider Mechanismen in einen automobilen Kontext. Dazu gehören eine Analyse der Antwortzeiten sowie eine Diskussion über bestimmte Herausforderungen bei der Implementierung. Beide Mechanismen werden in einer Prototyp Implementierung evaluiert und die Ergebnisse präsentiert

CD11b regulates fungal outgrowth but not neutrophil recruitment in a mouse model of invasive pulmonary aspergillosis

ß2 integrin receptors consist of an alpha subunit (CD11a-CD11d) and CD18 as the common beta subunit subunit, and are differentially expressed by leukocytes. ß2 integrins are required for cell-cell interaction interaction, transendothelial migration, uptake of opsonized pathogens, and cell signaling processe