Universality class of the pair contact process with diffusion

The pair contact process with diffusion (PCPD) is studied with a standard Monte Carlo approach and with simulations at fixed densities. A standard analysis of the simulation results, based on the particle densities or on the pair densities, yields inconsistent estimates for the critical exponents. However, if a well-chosen linear combination of the particle and pair densities is used, leading corrections can be suppressed, and consistent estimates for the independent critical exponents delta=0.16(2), beta=0.28(2) and z=1.58 are obtained. Since these estimates are also consistent with their values in directed percolation (DP), we conclude that PCPD falls in the same universality class as DP.Comment: 8 pages, 8 figures, accepted by Phys. Rev. E (not yet published

No impact of instructions and feedback on task integration in motor learning

This study examined the effect of instructions and feedback on the integration of two tasks. Task-integration of covarying tasks are thought to help dual-task performance. With complete task integration of covarying dual tasks, a dual-task becomes more like a single task and dual-task costs should be reduced as it is no longer conceptualized as a dual task. We covaried a tracking task with an auditory go/no-go task and tried to manipulate the extent of task-integration by using two different sets of instructions and feedback. A group receiving task-integration promoting instructions and feedback (N = 18) and a group receiving task-separation instructions and feedback (N = 20) trained a continuous tracking task. The tracking task covaried with the auditory go/no-go reaction time task because high-pitch sounds always occurred 250 ms before turns, which has been demonstrated to foster task integration before. The tracking task further contained a repeating segment to investigate implicit learning. Results showed that neither instructions, feedback, nor participants’ conceptualization of performing a single task vs. a dual task significantly affected task-integration. However, the covariation manipulation improved performance in both the tracking and the go/no-go task, exceeding performance in non-covarying and single tasks. We conclude that task-integration between covarying motor tasks is a robust phenomenon that is not influenced by instructions or feedback

How visual information influences dual-task driving and tracking

The study examined the impact of visual predictability on dual-task performance in driving and tracking tasks. Participants (N = 27) performed a simulated driving task and a pursuit tracking task. In either task, visual predictability was manipulated by systematically varying the amount of advance visual information: in the driving task, participants drove at night with low beam, at night with high beam, or in daylight; in the tracking task, participants saw a white line that specified the future target trajectory for 200, 400 or 800 ms. Concurrently with driving or tracking, participants performed an auditory task. They had to discriminate between two sounds and press a pedal upon hearing the higher sound. Results show that in general, visual predictability benefited driving and tracking; however, dual-task driving performance was best with highest visual predictability (daylight), dual-task tracking performance was best with medium visual predictability (400 ms). Braking/reaction times were higher in dual tasks compared to single tasks, but were unaffected by visual predictability, showing that its beneficial effects did not transfer to the auditory task. In both tasks, manual accuracy decreased around the moment the foot pressed the pedal, indicating interference between tasks. We, therefore, conclude that despite a general beneficial impact of predictability, the integration of visual information seems to be rather task specific, and that interference between driving and audiomotor tasks, and tracking and audiomotor tasks, seems comparable

What is a task? An ideomotor perspective

Although multitasking has been the subject of a large number of papers and experiments, the term task is still not well defined. In this opinion paper, we adopt the ideomotor perspective to define the term task and distinguish it from the terms goal and “action”. In our opinion, actions are movements executed by an actor to achieve a concrete goal. Concrete goals are represented as anticipated sensory consequences that are associated with an action in an ideomotor manner. Concrete goals are nested in a hierarchy of more and more abstract goals, which form the context of the corresponding action. Finally tasks are depersonalized goals, i.e., goals that should be achieved by someone. However tasks can be assigned to a specific person or group of persons, either by a third party or by the person or the group of persons themselves. By accepting this assignment the depersonalized task becomes a personal goal. In our opinion, research on multitasking needs to confine its scope to the analysis of concrete tasks, which result in concrete goals as anticipated sensory consequences of the corresponding action. We further argue that the distinction between dual- and single-tasking is dependent on the subjective conception of the task assignment, the goal representation and previous experience. Finally, we conclude that it is not the tasks, but the performing of the tasks, i.e. the actions that cause costs in multi-tasking experiments

Why prediction matters in multitasking and how predictability can improve it

This Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission. Prediction1 is an omnipresent principle of human behavior that can be fostered by predictability in the environment. We regard prediction as the mental representation of future event states or anticipated action consequences, and predictability as a property of certain events in the environment. On the assumption that predictability and prediction are beneficial for any kind of behavior, we argue that their benefits to relieving the human system are most evident when encountering multiple tasks. However, we predicate that their impact on multitasking is understudied and so we aim at dissociating prediction and predictability within multitasking contexts and at outlining different sources of predictability that have not been conflated under this term so far. From our opinion it follows that future multitasking research requires experimental designs and analyses that consider and unveil principles of prediction and the impact of predictability on multitasking performance

Tigecycline in critically ill patients on continuous renal replacement therapy: a population pharmacokinetic study

Background: Tigecycline is a vital antibiotic treatment option for infections caused by multiresistant bacteria in the intensive care unit (ICU). Acute kidney injury (AKI) is a common complication in the ICU requiring continuous renal replacement therapy (CRRT), but pharmacokinetic data for tigecycline in patients receiving CRRT are lacking. Methods: Eleven patients mainly with intra-abdominal infections receiving either continuous veno-venous hemodialysis (CVVHD, n = 8) or hemodiafiltration (CVVHDF, n = 3) were enrolled, and plasma as well as effluent samples were collected according to a rich sampling schedule. Total and free tigecycline was determined by ultrafiltration and high-performance liquid chromatography (HPLC)-UV. Population pharmacokinetic modeling using NONMEM® 7.4 was used to determine the pharmacokinetic parameters as well as the clearance of CVVHD and CVVHDF. Pharmacokinetic/pharmacodynamic target attainment analyses were performed to explore the potential need for dose adjustments of tigecycline in CRRT. Results: A two-compartment population pharmacokinetic (PK) model was suitable to simultaneously describe the plasma PK and effluent measurements of tigecycline. Tigecycline dialysability was high, as indicated by the high mean saturation coefficients of 0.79 and 0.90 for CVVHD and CVVHDF, respectively, and in range of the concentration-dependent unbound fraction of tigecycline (45–94%). However, the contribution of CRRT to tigecycline clearance (CL) was only moderate (CLCVVHD: 1.69 L/h, CLCVVHDF: 2.71 L/h) in comparison with CLbody (physiological part of the total clearance) of 18.3 L/h. Bilirubin was identified as a covariate on CLbody in our collective, reducing the observed interindividual variability on CLbody from 58.6% to 43.6%. The probability of target attainment under CRRT for abdominal infections was ≥ 0.88 for minimal inhibitory concentration (MIC) values ≤ 0.5 mg/L and similar to patients without AKI. Conclusions: Despite high dialysability, dialysis clearance displayed only a minor contribution to tigecycline elimination, being in the range of renal elimination in patients without AKI. No dose adjustment of tigecycline seems necessary in CRRT. Trial registration: EudraCT, 2012–005617-39. Registered on 7 August 2013

Dissolved Organic Carbon in the North Atlantic Meridional Overturning Circulation

The quantitative role of the Atlantic Meridional Overturning Circulation (AMOC) in dissolved organic carbon (DOC) export is evaluated by combining DOC measurements with observed water mass transports. In the eastern subpolar North Atlantic, both upper and lower limbs of the AMOC transport high-DOC waters. Deep water formation that connects the two limbs of the AMOC results in a high downward export of non-refractory DOC (197 Tg-C·yr-1). Subsequent remineralization in the lower limb of the AMOC, between subpolar and subtropical latitudes, consumes 72% of the DOC exported by the whole Atlantic Ocean. The contribution of DOC to the carbon sequestration in the North Atlantic Ocean (62 Tg-C·yr-1) is considerable and represents almost a third of the atmospheric CO 2 uptake in the region

ATM Modulates the Loading of Recombination Proteins onto a Chromosomal Translocation Breakpoint Hotspot

Chromosome translocations induced by DNA damaging agents, such as ionizing radiation and certain chemotherapies, alter genetic information resulting in malignant transformation. Abrogation or loss of the ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, increases the incidence of chromosome translocations. However, how ATM protects cells from chromosome translocations is still unclear. Chromosome translocations involving the MLL gene on 11q23 are the most frequent chromosome abnormalities in secondary leukemias associated with chemotherapy employing etoposide, a topoisomerase II poison. Here we show that ATM deficiency results in the excessive binding of the DNA recombination protein RAD51 at the translocation breakpoint hotspot of 11q23 chromosome translocation after etoposide exposure. Binding of Replication protein A (RPA) and the chromatin remodeler INO80, which facilitate RAD51 loading on damaged DNA, to the hotspot were also increased by ATM deficiency. Thus, in addition to activating DNA damage signaling, ATM may avert chromosome translocations by preventing excessive loading of recombinational repair proteins onto translocation breakpoint hotspots

Dosage Effects of Cohesin Regulatory Factor PDS5 on Mammalian Development: Implications for Cohesinopathies

Cornelia de Lange syndrome (CdLS), a disorder caused by mutations in cohesion proteins, is characterized by multisystem developmental abnormalities. PDS5, a cohesion protein, is important for proper chromosome segregation in lower organisms and has two homologues in vertebrates (PDS5A and PDS5B). Pds5B mutant mice have developmental abnormalities resembling CdLS; however the role of Pds5A in mammals and the association of PDS5 proteins with CdLS are unknown. To delineate genetic interactions between Pds5A and Pds5B and explore mechanisms underlying phenotypic variability, we generated Pds5A-deficient mice. Curiously, these mice exhibit multiple abnormalities that were previously observed in Pds5B-deficient mice, including cleft palate, skeletal patterning defects, growth retardation, congenital heart defects and delayed migration of enteric neuron precursors. They also frequently display renal agenesis, an abnormality not observed in Pds5B−/− mice. While Pds5A−/− and Pds5B−/− mice die at birth, embryos harboring 3 mutant Pds5 alleles die between E11.5 and E12.5 most likely of heart failure, indicating that total Pds5 gene dosage is critical for normal development. In addition, characterization of these compound homozygous-heterozygous mice revealed a severe abnormality in lens formation that does not occur in either Pds5A−/− or Pds5B−/− mice. We further identified a functional missense mutation (R1292Q) in the PDS5B DNA-binding domain in a familial case of CdLS, in which affected individuals also develop megacolon. This study shows that PDS5A and PDS5B functions other than those involving chromosomal dynamics are important for normal development, highlights the sensitivity of key developmental processes on PDS5 signaling, and provides mechanistic insights into how PDS5 mutations may lead to CdLS

Inhibitor of caspase-activated DNase expression enhances caspase-activated DNase expression and inhibits oxidative stress-induced chromosome breaks at the mixed lineage leukaemia gene in nasopharyngeal carcinoma cells

BACKGROUND: Nasopharyngeal carcinoma (NPC) is commonly found in Asia, especially among the Chinese ethnic group. Chromosome rearrangements are common among NPC patients. Although the mechanism underlying the chromosome rearrangements in NPC is unclear, various mechanisms including activation of caspase-activated DNase (CAD) were proposed to contribute to chromosome rearrangements in leukaemia. Activation of CAD can be initiated by multiple agents, including oxidative stress, which is well implicated in carcinogenesis. CAD is the main enzyme that causes DNA fragmentation during apoptosis, and CAD is also implicated in promoting cell differentiation. In view of the role of oxidative stress in carcinogenesis and CAD activation, and since CAD was suggested to contribute to chromosome rearrangement in leukaemia, we hypothesise that oxidative stress-induced CAD activation could be one of the mechanisms that leads to chromosome rearrangements in NPC. METHODS: SUNEI cells were treated with various concentrations of H(2)O(2) for different period of time to ensure that cells undergo H(2)O(2)-induced MLL gene cleavage. Transfections with hCAD, mCAD, mutant hCAD, or cotransfection with hCAD and mICAD, and cotransfection with mutant hCAD and mICAD were performed. Gene expression was confirmed by Western blotting and MLL gene cleavage was assessed by inverse polymerase chain reaction (IPCR). RESULTS: Treatment with H(2)O(2) clearly induces cleavages within the MLL gene which locates at 11q23, a common deletion site in NPC. In order to investigate the role of CAD, CAD was overexpressed in SUNE1 cells, but that did not result in significant changes in H(2)O(2)-induced MLL gene cleavage. This could be because CAD requires ICAD for proper folding. Indeed, by overexpressing ICAD alone or co-expressing ICAD with CAD, Western blotting showed that CAD was expressed. In addition, ICAD overexpression also suppressed H(2)O(2)-induced MLL gene cleavage, suggesting a possible role of CAD in initiating chromosome cleavage during oxidative stress. CONCLUSIONS: Oxidative stress mediated by H(2)O(2) induces cleavage of the MLL gene, most likely via the caspase-activated DNase, CAD, and CAD expression requires ICAD. Since the MLL gene is located at 11q23, a common deletion site in NPC, thus stress-induced CAD activation may represent one of the mechanisms leading to chromosome rearrangement in NPC