An examination of the metabolic processes underpinning critical swimming in Atlantic cod (Gadus morhua L.) using in vivo 31P-NMR spectroscopy.

Traditionally, critical swimming speed has been defined as the speed when a fish can no longer propel itself forward, and is exhausted. To gain a better understanding of the metabolic processes at work during a U(crit) swim test, and that lead to fatigue, we developed a method using in vivo (31)P-NMR spectroscopy in combination with a Brett-type swim tunnel. Our data showed that a metabolic transition point is reached when the fish change from using steady state aerobic metabolism to non-steady state anaerobic metabolism, as indicated by a significant increase in inorganic phosphate levels from 0.3+/-0.3 to 9.5+/-3.4 mol g(-1), and a drop in intracellular pH from 7.48+/-0.03 to 6.81+/-0.05 in muscle. This coincides with the point when the fish change gait from subcarangiform swimming to kick-and-glide bursts. As the number of kicks increased, so too did the Pi concentration, and the pH(i) dropped. Both changes were maximal at U(crit). A significant drop in Gibbs free energy change of ATP hydrolysis from -55.6+/-1.4 to -49.8+/-0.7 kJ mol(-1) is argued to have been involved in fatigue. This confirms earlier findings that the traditional definition of U(crit), unlike other critical points that are typically marked by a transition from aerobic to anaerobic metabolism, is the point of complete exhaustion of both aerobic and anaerobic resources.

Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms: a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST action BM0902) study.

Reliable detection of JAK2-V617F is critical for accurate diagnosis of myeloproliferative neoplasms (MPNs); in addition, sensitive mutation-specific assays can be applied to monitor disease response. However, there has been no consistent approach to JAK2-V617F detection, with assays varying markedly in performance, affecting clinical utility. Therefore, we established a network of 12 laboratories from seven countries to systematically evaluate nine different DNA-based quantitative PCR (qPCR) assays, including those in widespread clinical use. Seven quality control rounds involving over 21,500 qPCR reactions were undertaken using centrally distributed cell line dilutions and plasmid controls. The two best-performing assays were tested on normal blood samples (n=100) to evaluate assay specificity, followed by analysis of serial samples from 28 patients transplanted for JAK2-V617F-positive disease. The most sensitive assay, which performed consistently across a range of qPCR platforms, predicted outcome following transplant, with the mutant allele detected a median of 22 weeks (range 6-85 weeks) before relapse. Four of seven patients achieved molecular remission following donor lymphocyte infusion, indicative of a graft vs MPN effect. This study has established a robust, reliable assay for sensitive JAK2-V617F detection, suitable for assessing response in clinical trials, predicting outcome and guiding management of patients undergoing allogeneic transplant.

Transconvolution and the virtual positron emission tomograph--a new method for cross calibration in quantitative PET∕CT imaging

PURPOSE Positron emission tomography (PET)∕computed tomography (CT) measurements on small lesions are impaired by the partial volume effect, which is intrinsically tied to the point spread function of the actual imaging system, including the reconstruction algorithms. The variability resulting from different point spread functions hinders the assessment of quantitative measurements in clinical routine and especially degrades comparability within multicenter trials. To improve quantitative comparability there is a need for methods to match different PET∕CT systems through elimination of this systemic variability. Consequently, a new method was developed and tested that transforms the image of an object as produced by one tomograph to another image of the same object as it would have been seen by a different tomograph. The proposed new method, termed Transconvolution, compensates for differing imaging properties of different tomographs and particularly aims at quantitative comparability of PET∕CT in the context of multicenter trials. METHODS To solve the problem of image normalization, the theory of Transconvolution was mathematically established together with new methods to handle point spread functions of different PET∕CT systems. Knowing the point spread functions of two different imaging systems allows determining a Transconvolution function to convert one image into the other. This function is calculated by convolving one point spread function with the inverse of the other point spread function which, when adhering to certain boundary conditions such as the use of linear acquisition and image reconstruction methods, is a numerically accessible operation. For reliable measurement of such point spread functions characterizing different PET∕CT systems, a dedicated solid-state phantom incorporating (68)Ge∕(68)Ga filled spheres was developed. To iteratively determine and represent such point spread functions, exponential density functions in combination with a Gaussian distribution were introduced. Furthermore, simulation of a virtual PET system provided a standard imaging system with clearly defined properties to which the real PET systems were to be matched. A Hann window served as the modulation transfer function for the virtual PET. The Hann's apodization properties suppressed high spatial frequencies above a certain critical frequency, thereby fulfilling the above-mentioned boundary conditions. The determined point spread functions were subsequently used by the novel Transconvolution algorithm to match different PET∕CT systems onto the virtual PET system. Finally, the theoretically elaborated Transconvolution method was validated transforming phantom images acquired on two different PET systems to nearly identical data sets, as they would be imaged by the virtual PET system. RESULTS The proposed Transconvolution method matched different PET∕CT-systems for an improved and reproducible determination of a normalized activity concentration. The highest difference in measured activity concentration between the two different PET systems of 18.2% was found in spheres of 2 ml volume. Transconvolution reduced this difference down to 1.6%. In addition to reestablishing comparability the new method with its parameterization of point spread functions allowed a full characterization of imaging properties of the examined tomographs. CONCLUSIONS By matching different tomographs to a virtual standardized imaging system, Transconvolution opens a new comprehensive method for cross calibration in quantitative PET imaging. The use of a virtual PET system restores comparability between data sets from different PET systems by exerting a common, reproducible, and defined partial volume effect.

Terminal short arm domains of basement membrane laminin are critical for its self-assembly

Laminin self-assembles into large polymers by a cooperative two-step calcium-dependent mechanism (Yurchenco, P. D., E. C. Tsilibary, A. S. Charonis, and H. Furthmayr. 1985. J. Biol. Chem. 260:7636-7644). The domain specificity of this process was investigated using defined proteolytically generated fragments corresponding to the NH2-terminal globule and adjacent stem of the short arm of the B1 chain (E4), a complex of the two short arms of the A and B2 chains attached to the proximal stem of a third short arm (E1'), a similar complex lacking the globular domains (P1'), and the distal half of the long arm attached to the adjacent portion of the large globule (E8). Polymerization, followed by an increase of turbidity at 360 nm in neutral isotonic TBS containing CaCl2 at 35 degrees C, was quantitatively inhibited in a concentration-dependent manner with laminin fragments E4 and E1' but not with fragments E8 and P1'. Affinity retardation chromatography was used for further characterization of the binding of laminin domains. The migration of fragment E4, but not of fragments E8 and P1', was retarded in a temperature- and calcium-dependent fashion on a laminin affinity column but not on a similar BSA column. These data are evidence that laminin fragments E4 and E1' possess essential terminal binding domains for the self-aggregation of laminin, while fragments E8 and P1' do not. Furthermore, the individual domain-specific interactions that contribute to assembly are calcium dependent and of low affinity.

A hybrid method for large-scale short-term scheduling of make-and-pack production processes

Due to the ongoing trend towards increased product variety, fast-moving consumer goods such as food and beverages, pharmaceuticals, and chemicals are typically manufactured through so-called make-and-pack processes. These processes consist of a make stage, a pack stage, and intermediate storage facilities that decouple these two stages. In operations scheduling, complex technological constraints must be considered, e.g., non-identical parallel processing units, sequence-dependent changeovers, batch splitting, no-wait restrictions, material transfer times, minimum storage times, and finite storage capacity. The short-term scheduling problem is to compute a production schedule such that a given demand for products is fulfilled, all technological constraints are met, and the production makespan is minimised. A production schedule typically comprises 500–1500 operations. Due to the problem size and complexity of the technological constraints, the performance of known mixed-integer linear programming (MILP) formulations and heuristic approaches is often insufficient. We present a hybrid method consisting of three phases. First, the set of operations is divided into several subsets. Second, these subsets are iteratively scheduled using a generic and flexible MILP formulation. Third, a novel critical path-based improvement procedure is applied to the resulting schedule. We develop several strategies for the integration of the MILP model into this heuristic framework. Using these strategies, high-quality feasible solutions to large-scale instances can be obtained within reasonable CPU times using standard optimisation software. We have applied the proposed hybrid method to a set of industrial problem instances and found that the method outperforms state-of-the-art methods.

Public service motivation and performance: a critical perspective

Purpose – A growing body of literature points to the importance of public service motivation (PSM) for the performance of public organizations. The purpose of this paper is to assess the method predominantly used for studying this linkage by comparing the findings it yields without and with a correction suggested by Brewer (2006), which removes the common-method bias arising from employee-specific response tendencies. Design/methodology/approach – First, the authors conduct a systematic review of published empirical research on the effects of PSM on performance and show that all studies found have been conducted at the individual level. Performance indicators in all but three studies were obtained by surveying the same employees who were also asked about their PSM. Second, the authors conduct an empirical analysis. Using survey data from 240 organizational units within the Swiss federal government, the paper compares results from an individual-level analysis (comparable to existing research) to two analyses where the data are aggregated to the organizational level, one without and one with the correction for common-method bias suggested by Brewer (2006). Findings – Looking at the Attraction to Policy-Making dimension of PSM, there is an interesting contrast: While this variable is positively correlated with performance in both the individual-level analysis and the aggregated data analysis without the correction for common-method bias, it is not statistically associated with performance in the aggregated data analysis with the correction. Originality/value – The analysis is the first to assess the robustness of the performance-PSM linkage to a correction for common-method bias. The findings place the validity of at least one part of the individual-level linkage between PSM and performance into question.

Comparison of the critical shoulder angle in radiographs and computed tomography.

OBJECTIVE The critical shoulder angle (CSA) is an indicator of degenerative shoulder pathologies. CSAs above 35° are associated with degenerative rotator cuff disease, whereas values below 30° are common in osteoarthritis of the glenohumeral joint. Measurements are usually performed on radiographs; however, no data have been reported regarding the reliability of CT scan measurements between different readers or the reproducibility of measurements from radiographs to CT scans. The purpose of our study was to clarify whether CSA measurements on radiographs and CT scans of the same patients show similar values. MATERIALS AND METHODS CSA measurements of 60 shoulders (59 patients) were performed on radiographs and multiplanar reconstructions of corresponding CT scans. Inter-reader reliability and inter-method correlation were calculated. RESULTS The mean discrepancy between readers was only 0.2° (SD ±1.0°) on radiographs. CT scan measurements showed a mean discrepancy of 0.3° (SD ±1.2°). The inter-reader reliability was 0.993 for radiographs and 0.989 for CT scans. There was a very strong inter-method correlation between the CSA measured on radiographs and CT scans (Spearman's rho = 0.974). The mean differences between angles on radiographs and CT measurements were -0.05° (SD ±1.2°) and 0.1° (SD ±1.2°), respectively. CONCLUSION Measurements of the CSA on anterior-posterior radiographs and CT scans are highly correlated, and inter-modality differences are negligible.

Development of a new real-time polymerase chain reaction assay to detect Duck adenovirus A DNA and application to samples from Swiss poultry flocks.

Between 2008 and 2012, commercial Swiss layer and layer breeder flocks experiencing problems in laying performance were sampled and tested for infection with Duck adenovirus A (DAdV-A; previously known as Egg drop syndrome 1976 virus). Organ samples from birds sent for necropsy as well as blood samples from living animals originating from the same flocks were analyzed. To detect virus-specific DNA, a newly developed quantitative real-time polymerase chain reaction method was applied, and the presence of antibodies against DAdV-A was tested using a commercially available enzyme-linked immunosorbent assay. In 5 out of 7 investigated flocks, viral DNA was detected in tissues. In addition, antibodies against DAdV-A were detected in all of the flocks.

Critical Issues of Centralized and Cloudified LTE-FDD Radio Access Networks

Cloudification of the Centralized-Radio Access Network (C-RAN) in which signal processing runs on general purpose processors inside virtual machines has lately received significant attention. Due to short deadlines in the LTE Frequency Division Duplex access method, processing time fluctuations introduced by the virtualization process have a deep impact on C-RAN performance. This paper evaluates bottlenecks of the OpenAirInterface (OAI is an open-source software-based implementation of LTE) cloud performance, provides feasibility studies on C-RAN execution, and introduces a cloud architecture that significantly reduces the encountered execution problems. In typical cloud environments, the OAI processing time deadlines cannot be guaranteed. Our proposed cloud architecture shows good characteristics for the OAI cloud execution. As an example, in our setup more than 99.5% processed LTE subframes reach reasonable processing deadlines close to performance of a dedicated machine.

Allele-specific polymerase chain reaction diagnostic test for the functional MDR1 polymorphism in dogs

The major multidrug transporter P-glycoprotein (Pgp) contributes to the barrier function of several tissues and organs, including the brain. In a subpopulation of Collies and seven further dog breeds, a 4 base pair deletion has been described in the Pgp-encoding MDR1 gene. This deletion results in the absence of a functional form of Pgp and loss of its protective function. Severe intoxication with the Pgp substrate ivermectin has been attributed to the genetically determined lack of Pgp. An allele-specific polymerase chain reaction (PCR)-based screening method has been developed to detect the mutant allele and to determine if a dog is homozygous or heterozygous for the mutation. Based on this validation, the allele-specific PCR proved to be a robust, reproducible and specific tool, allowing rapid determination of the MDR1 genotype of dogs of at risk breeds using blood samples or buccal swabs.

Critical point and scale setting in SU(3) plasma: An update

We explore a method developed in statistical physics which has been argued to have exponentially small finite-volume effects, in order to determine the critical temperature Tc of pure SU(3) gauge theory close to the continuum limit. The method allows us to estimate the critical coupling βc of the Wilson action for temporal extents up to Nτ∼20 with ≲0.1% uncertainties. Making use of the scale setting parameters r0 and t0−−√ in the same range of β-values, these results lead to the independent continuum extrapolations Tcr0=0.7457(45) and Tct0−−√=0.2489(14), with the latter originating from a more convincing fit. Inserting a conversion of r0 from literature (unfortunately with much larger errors) yields Tc/ΛMS¯¯¯¯¯=1.24(10).

Amygdala response to self-critical stimuli and symptom improvement in psychotherapy for depression

Background: Cognitive–behavioural therapy is efficacious in the treatment of major depressive disorder but response rates are still far from satisfactory. Aims: To better understand brain responses to individualised emotional stimuli and their association with outcome, to enhance treatment. Method: Functional magnetic resonance imaging data were collected prior to individual psychotherapy. Differences in brain activity during passive viewing of individualised self-critical material in 23 unmedicated out-patients with depression and 28 healthy controls were assessed. The associations between brain activity, cognitive and emotional change, and outcome were analysed in 21 patients. Results: Patients showed enhanced activity in the amygdala and ventral striatum compared with the control group. Non-response to therapy was associated with enhanced activity in the right amygdala compared with those who responded, and activity in this region was negatively associated with outcome. Emotional but not cognitive changes mediated this association. Conclusions: Amygdala hyperactivity may lessen symptom improvement in psychotherapy for depression through attenuating emotional skill acquisition.

Wright’s Version of Critical Realism

N. T. Wright’s research project “Christian Origins and the Question of God” is characterized by its use of the method of critical realism. Now, “critical realism” is a term that has been used in connection with different epistemo-logical positions because the term has been “constantly reinvented.” It is very easy to make up a term when one wants to distinguish oneself from an assumed naïve approach to reality. As has been observed earlier, the use of a distinct term does not necessarily mean the same if used by another author; the context is important. One has to track literal dependencies to evaluate whether continuity with former uses of a term is intended. That is to say, the term “critical realism” has proven to be equivocal, although this has rarely been noticed . This does not mean that taking such a critical realist stance cannot present a decisive advantage over rather unreflective approaches to whatever sort of reality. Nevertheless, philosophically it can probably only be a start. The purpose of this contribution to this compendium will be to analyze the content claims and the status of N. T. Wright’s critical realism in these regards, with a special emphasis on Paul and the Faithfulness of God, of course.

The effects of long (C20/22) and short (C18) chain omega-3 fatty acids on keel bone fractures, bone biomechanics, behavior, and egg production in free-range laying hens.

Keel fractures in the laying hen are the most critical animal welfare issue facing the egg production industry, particularly with the increased use of extensive systems in response to the 2012 EU directive banning conventional battery cages. The current study is aimed at assessing the effects of 2 omega-3 (n3) enhanced diets on bone health, production endpoints, and behavior in free-range laying hens. Data was collected from 2 experiments over 2 laying cycles, each of which compared a (n3) supplemented diet with a control diet. Experiment 1 employed a diet supplemented with a 60:40 fish oil-linseed mixture (n3:n6 to 1.35) compared with a control diet (n3:n6 to 0.11), whereas the n3 diet in Experiment 2 was supplemented with a 40:60 fish oil-linseed (n3:n6 to 0.77) compared to the control diet (n3:n6 to 0.11). The n3 enhanced diet of Experiment 1 had a higher n3:n6 ratio, and a greater proportion of n3 in the long chain (C20/22) form (0.41 LC:SC) than that of Experiment 2 (0.12 LC:SC). Although dietary treatment was successful in reducing the frequency of fractures by approximately 27% in Experiment 2, data from Experiment 1 indicated the diet actually induced a greater likelihood of fracture (odds ratio: 1.2) and had substantial production detriment. Reduced keel breakage during Experiment 2 could be related to changes in bone health as n3-supplemented birds demonstrated greater load at failure of the keel, and tibiae and humeri that were more flexible. These results support previous findings that n3-supplemented diets can reduce fracture likely by increasing bone strength, and that this can be achieved without detriment to production. However, our findings suggest diets with excessive quantities of n3, or very high levels of C20/22, may experience health and production detriments. Further research is needed to optimize the quantity and type of n3 in terms of bone health and production variables and investigate the potential associated mechanisms.

Selecting Contexts. One Method of Selecting Contexts for Theatre Historiography

In principle, the world and life itself are the contexts of theatrical events. The term context is broad and thus seems hardly usable. It only makes sense to use the term when terminologies and methodologies determine which parts of their contexts are to be incorporated and analysed for which theatrical event. This presentation exemplifies a method which is particularly suitable for sensibly selecting the most important contexts for research in theatre history. The complexity of the representation increases continuously from The Presentation of Self in Everyday Life to Brecht’s “Street Scene” and “Everyday Theatre”, portrayals of rulers in feasts and parades to Hamlet productions by the Royal Shakespeare Company or a Wagner opera in Bayreuth. The different forms of theatre thus constitute a continuum which spans from “everyday theatre” to “art theatre”. The representation of the world in this continuum is sometimes questioned by the means of theatre, for example when Commedia dell’arte takes a critical stance towards the representative theatre of the humanists or when playful devices such as reversal, parody and fragmentation challenge the representative character of productions, which is applied by the Vice character for instance. There is a second component that has an impact on the continuum without a theatrical device: attitude, opinion, norms and bans which originate from society. As excerpts of contexts, they refer to single forms of theatre in the continuum. This results in a complex system of four components which evolves from the panorama between the antipodes “everyday theatre” and “art theatre” as well as both spheres of influence of which only one uses theatrical devices. All components interact in a specific time frame in a specific place in a specific way in each case, which can then be described as the theatricality in this time frame. This presentation will deal with what the concept is capable of doing.