Peter Strawson’s ‘Freedom and Resentment’ (1962) has reoriented the way moral philosophers think about responsibility. There is a general sense that Strawson’s approach holds the promise that we may move beyond the traditional discussion of free will in recognition of the fact that whether determinism is true is irrelevant for whether we are responsible beings. This is Strawson’s Promise. This the

Target-controlled infusion (TCI) constitutes a clinically available alternative to manually administering the infusion rate of the anesthetic drug propofol. In TCI, a drug infusion profile is optimized to track a reference trajectory of blood plasma or effect site (brain cortex) drug concentration, or a corresponding clinical effect. TCI is a pure feed-forward openloop strategy, fully reliant on a

ObjectiveTo study the cumulative live birth rate (CLBR) after the first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment in women with or without deep-infiltrating endometriosis (DIE) and/or endometrioma diagnosed by transvaginal ultrasonography (TVUS), using the International Deep Endometriosis Analysis (IDEA) group definitions.DesignProspective observational coho

IntroductionStudies that use standardized ultrasonographic criteria to diagnose adenomyosis in subfertile women are needed. These would improve the understanding of the disease burden and enable further studies on its impact on fertility and assisted reproductive treatment (ART) outcome. The aim of this study was to determine the prevalence of different features of adenomyosis in women scheduled f

Inactivation of the yeast nonsense-mediated mRNA decay (NMD) pathway stabilizes nonsense mRNAs and promotes readthrough of premature translation termination codons. Although the latter phenotype is thought to reflect a direct role of NMD factors in translation termination, its mechanism is unknown. Here we show that the reduced termination efficiency of NMD-deficient cells is attributable to incre

The conserved pre-mRNA retention and splicing (RES) complex, which in yeast consists of Bud13p, Snu17p and Pml1p, is thought to promote nuclear retention of unspliced pre-mRNAs and enhance splicing of a subset of transcripts. Here, we find that the absence of Bud13p or Snu17p causes greatly reduced levels of the modified nucleoside N(4)-acetylcytidine (ac(4)C) in tRNA and that a lack of Pml1p redu

The translational decoding properties of tRNAs are modulated by naturally occurring modifications of their nucleosides. Uridines located at the wobble position (nucleoside 34 [U(34)]) in eukaryotic cytoplasmic tRNAs often harbor a 5-methoxycarbonylmethyl (mcm(5)) or a 5-carbamoylmethyl (ncm(5)) side chain and sometimes an additional 2-thio (s(2)) or 2'-O-methyl group. Although a variety of models

Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that detects and degrades transcripts containing premature translation termination codons. Gene expression profiling experiments have shown that inactivation of the NMD pathway leads to the accumulation of both aberrant, nonsense-containing mRNAs, and many apparently wild-type transcripts. Such increases in transcript steady-state leve

The Saccharomyces cerevisiae Elongator complex consisting of the six Elp1-Elp6 proteins has been proposed to participate in three distinct cellular processes: transcriptional elongation, polarized exocytosis, and formation of modified wobble uridines in tRNA. Therefore it was important to clarify whether Elongator has three distinct functions or whether it regulates one key process that leads to m

Kluyveromyces lactis killer strains secrete a heterotrimeric toxin (zymocin), which causes an irreversible growth arrest of sensitive yeast cells. Despite many efforts, the target(s) of the cytotoxic gamma-subunit of zymocin has remained elusive. Here we show that three tRNA species tRNA(Glu)(mcm(5)s(2)UUC), tRNA(Lys)(mcm(5)s(2)UUU), and tRNA(Gln)(mcm(5)s(2)UUG) are the targets of gamma-toxin. The

Elongator has been reported to be a histone acetyltransferase complex involved in elongation of RNA polymerase II transcription. In Saccharomyces cerevisiae, mutations in any of the six Elongator protein subunit (ELP1-ELP6) genes or the three killer toxin insensitivity (KTI11-KTI13) genes cause similar pleiotropic phenotypes. By analyzing modified nucleosides in individual tRNA species, we show th

The biogenesis of transfer RNA is a process that requires many different factors. In this study, we describe a genetic screen aimed to identify gene products participating in this process. By screening for mutations lethal in combination with a sup61-T47:2C allele, coding for a mutant form of, the nonessential TAN1 gene was identified. We show that the TAN1 gene product is required for formation o

A 5-methyluridine (m(5)U) residue at position 54 is a conserved feature of bacterial and eukaryotic tRNAs. The methylation of U54 is catalyzed by the tRNA(m5U54)methyltransferase, which in Saccharomyces cerevisiae is encoded by the nonessential TRM2 gene. In this study, we identified four different strains with mutant forms of tRNA(Ser)CGA. The absence of the TRM2 gene in these strains decreased t

The presence of 5-methyluridine (m5U) at position 54 is a ubiquitous feature of most bacterial and eukaryotic elongator tRNAs. In this study, we have identified and characterized the TRM2 gene that encodes the tRNA(m5U54)methyltransferase, responsible for the formation of this modified nucleoside in Saccharomyces cerevisiae. Transfer RNA isolated from TRM2-disrupted yeast strains does not contain

Objective: This study investigates whether and how perceived training value varies among fighter pilots participating in a large force exercise (LFE), and whether they expect Live Virtual Constructive (LVC) training to enhance training value of future LFEs. Background: LVC technology is maturing but its expected training value is under-investigated, especially regarding future LVC in LFEs. Method:

The potential of unmanned systems is vast, but pre-procurement evaluation is challenging. This study explores potential uses of and interaction with unmanned ground vehicles (UGVs) for dismounted infantry. A remote user study with Swedish Armed Forces personnel is described. Many factors influencing future use and interaction were found. Moreover, this study shows the potential of the innovative m

Combining Live, Virtual, and Constructive (LVC) aircraft in the same training scenario holds promise for developing and enhancing fighter pilot training. The simulator study reported here builds on joint pilot-researcher co-design work of beyond visual range LVC training (LVC-T) scenarios to provide training value to pilots in both Live and Virtual aircraft. One fourship of pilots simulated Live e

Ultra-safe organizations, such as Air Navigation Service Providers (ANSPs), have extensive safety management organizations and generally excellent safety records with very few serious incidents and accidents. This development has been supported by increasingly advanced and effective methods. However, recent research has uncovered how the application of even advanced incident investigation methods

Aviation is a highly inter-connected system. This means that a problem in one area may cause effects in other countries or parts of the Air Transport System (ATS). Examples range from local air traffic disruptions to the 2010 volcanic ash crisis. Agility, like resilience, refers to the ability to cope with dynamics and complexity in a flexible manner, by adjusting and adapting performance and the

Live virtual constructive (LVC) flight simulations mix pilots flying actual aircraft, pilots flying in simulators, and computer-generated forces, in joint scenarios. Training resources invested in LVC scenarios must give a high return, and therefore pilots in both live aircraft and simulators need to experience training value for the extensive resources invested in both, an aspect not emphasized i