Validity and reliability of evaluation procedures in comparative studies of effort prediction models

We have in previous studies reported our findings and concern about the reliability and validity of the evaluation procedures used in comparative studies on competing effort prediction models. In particular, we have raised concerns about the use of accuracy statistics to rank and select models. Our concern is strengthened by the observed lack of consistent findings. This study offers more insights into the causes of conclusion instability by elaborating on the findings of our previous work concerning the reliability and validity of the evaluation procedures. We show that model selection based on the accuracy statistics MMRE, MMER, MBRE, and MIBRE contribute to conclusion instability as well as selection of inferior models. We argue and show that the evaluation procedure must include an evaluation of whether the functional form of the prediction model makes sense to better prevent selection of inferior models.     

Viscosity reduction of isotonic solutions of the photosensitizer TPCS2a by cyclodextrin complexation

Meso-tetraphenyl chlorin disulphonate (TPCS_2a) is a photosensitizer (PS) particularly developed and patented for use in the technology of photochemical internalization (PCI) against cancer. TPCS_2a is known to aggregate in aqueous media even at low concentrations (≥0.1?µM) and to form a high-viscosity network at clinically relevant concentrations (mM). The aim of this work was to evaluate the effect of two hydroxypropylated cyclodextrin derivatives of beta and gamma type, respectively i.e. HPβCD and HPγCD, on the aggregation and solubilization of TPCS_2a in isotonic solutions. Samples containing micromolar concentrations of TPCS_2a were studied spectrophotometrically, while samples containing a clinical relevant concentration (10?mM?=?9?mg/ml) of TPCS_2a were evaluated by dynamic viscosity measurements. HPβCD was determined to be a more suitable solubilizer of TPCS_2a than HPγCD in aqueous media both in the absence and presence of salt. The complexation stoichiometry between TPCS_2a/HPβCD at micromolar to millimolar concentrations of TPCS_2a was determined to be 1:3 and 1:2 in the absence and presence of isotonic NaCl, respectively. The network of TPCS_2a (10?mM) was broken down in the presence of 3% w/v (=?20?mM) HPβCD, i.e. a 1:2 molar ratio between TPCS_2a and the cyclodextrin. Formation of the inclusion complex resulted in low viscosity samples both in water and in the presence of isotonic NaCl or phosphate buffered saline (PBS) at 25?°C and 37?°C.     

Unbound DHA causes a high blank value in β‐oxidation assay: a concern for in vitro studies

The information on binding capacity of different fatty acids (FAs) to albumin is incomplete, however, in the majority of in vitro experiments, FAs and albumin were simply mixed and their affinity believed to be complete. In this study, seven [1‐¹⁴C] FAs were mixed with albumin and assayed for β‐oxidation in rat liver homogenates. In the process of identifying the radioactive background of control assay by LCMS/MS, the results indicated different binding capacity of FAs to albumin. The percentage of unbound FAs recovered in clarified acidic solution was lower than 2% with 16:0 and 18:1n‐9, nearly 5% with EPA, 7% with 18:2n‐6, 18:3n‐3 and 20:4n‐6, and surprisingly high to 41% with DHA. Various FA/albumin molar ratios as well as different types of albumin only marginally affected these data. Thus, the big mass of unbound free DHA led to a high blank value, which is 60 times higher than the real value in the procedure of β‐oxidation measurement in vitro. In the design of future FA research in vitro, the binding capacity of FA to albumin or other proteins must be considered, especially for DHA research.     

Design ideas for IT in public spaces

This paper examines the usability issues involved in ticketless travelling with an airport train. The main contribution of this paper is that it describes actual use situations in detail. We show how users’ intentions are difficult to anticipate, unless in explicit communication, e.g., with people whose job it is to help out with using the system. Being conspicuously assisted, however, only aggravates a situation where users usually prefer anonymity. Given a “private in public” type of design, users had little chance of learning from watching others. Moreover, users were quickly annoyed when they struggled with the machine. They seemed to treat it as an agent for the provider rather than an assistant or tool for themselves. At the end of this paper, we outline and illustrate some new design ideas, which we think ought to be considered for future designs of IT in public spaces.     

CD40/APC-specific antibodies with three T-cell epitopes loaded in the constant domains induce CD4+ T-cell responses

CD4+ T lymphocytes play a central role in the orchestration and maintenance of the adaptive immune response. Targeting of antigen to antigen presenting cells (APCs) increases peptide loading of major histocompatibility complex (MHC) class II molecules and CD4+ T-cell activation. APCs have been targeted by APC-specific recombinant antibodies (rAbs) with single T-cell epitopes integrated in the constant region of the heavy chain (C(H)). However, the strategy may be improved if several T-cell epitopes could be delivered simultaneously by one rAb. We here demonstrate that a single rAb can be loaded with multiple identical or different T-cell epitopes, integrated as loops between β-strands in C(H) domains. One epitope was inserted in C(H)1, while two were placed in C(H)2 of IgG. T-cell proliferation assays showed that all three peptides were excised from loops and presented on MHC class II to T-cells. Induction of T-cell activation by each epitope in the multi-peptide rAb was as good, or even better, than that elicited by corresponding single-peptide rAbs. Furthermore, following DNA vaccination of mice with plasmids that encode CD40-specific rAbs loaded with either one or three peptides, T-cell responses were induced. Thus, integration of multiple epitopes in C(H) region loops of APC-specific rAbs is feasible and may be utilized in design of multi-vaccines.     

Yield,nitrogen recovery efficiency and quality of vegetables grown with organic waste-derived fertilisers

More sustainable production of high-quality, nutritious food is of worldwide interest. Increasing nutrient recycling into food systems is a step in this direction. The objective of the present study was to determine nitrogen (N) fertiliser effects of four waste-derived and organic materials in a cropping sequence of broccoli, potato and lettuce grown at two latitudes (58° and 67°N) in Norway during 3 years. Effects of anaerobically digested food waste (AD), shrimp shell (SS), algae meal (AM) and sheep manure (SM) at different N application rates (80 and 170 kg N ha^?1 for broccoli, and 80 and 60 kg N ha^?1 for potato and lettuce, respectively) and residual effects were tested on crop yield, N uptake, N recovery efficiency (NRE), N balance, N content in produce, mineral N in soil, product quality parameters and content of nitrate in lettuce. Mineral fertiliser (MF) served as control. Effects on yield, N uptake, NRE, N balance and product quality parameters could to a great extent be explained by estimated potentially plant-available N, which ranked in the order of AD > SS > SM > AM. Results for crops fertilised with AD and SS were not significantly different from MF at the same N application rate, while AM, in agreement with its negative effect on N mineralisation, gave negative or near-neutral effects compared to the control. No residual effect was detected after the year of application. The results showed that knowledge about N dynamics of relevant organic waste-derived fertilisers is necessary to decide on the timing and rate of application.     

β-oxidation capacity of red and white muscle and liver in Atlantic salmon (<Emphasis Type="Italic">Salmo salar</Emphasis> L.)—Effects of increasing dietary rapeseed oil and olive oil to replace capelin oil

Post-smolt Atlantic salmon (Salmo salar) were fed six diets in which capelin oil was replaced with 0, 25, 50, 75, or 100% rapeseed oil (RO; low-erucic acid) or 50% olive oil (OO). The experimental diets were fed to single groups of Atlantic salmon for 42 wk, whereas the 100% capelin oil (0% RO) diet was fed in duplicate. The β-oxidation capacity of palmitoyl-CoA was determined, using a method optimized for salmon tissues, at the start of the experiment, after 21 wk (October), and after 42 wk (March) in red and white muscle and in liver. Red muscle showed the highest specific β-oxidation capacity, but when expressed as total β-oxidation capacity for the whole tissue, white muscle was the most important tissue for the β-oxidation of FA. From the initial to the final sampling, the β-oxidation capacity of white muscle increased significantly, whereas the β-oxidation capacity in liver decreased significantly. After 22 wk, white muscle exhibited an increased β-oxidation capacity when the dietary RO content was raised from 25 to 75%, with similar effects in red muscle and liver after 42 wk of feeding. The present results also show that the β-oxidation capacity increased with an increase in fish size.     

Low-Dose-Rate Radiation-Induced Secretion of TGF-β3 Together with an Activator in Small Extracellular Vesicles Modifies Low-Dose Hyper-Radiosensitivity through ALK1 Binding

Hyper-radiosensitivity (HRS) is the increased sensitivity to low doses of ionizing radiation observed in most cell lines. We previously demonstrated that HRS is permanently abolished in cells irradiated at a low dose rate (LDR), in a mechanism dependent on transforming growth factor β3 (TGF-β3). In this study, we aimed to elucidate the activation and receptor binding of TGF-β3 in this mechanism. T-47D cells were pretreated with inhibitors of potential receptors and activators of TGF-β3, along with addition of small extracellular vesicles (sEVs) from LDR primed cells, before their radiosensitivity was assessed by the clonogenic assay. The protein content of sEVs from LDR primed cells was analyzed with mass spectrometry. Our results show that sEVs contain TGF-β3 regardless of priming status, but only sEVs from LDR primed cells remove HRS in reporter cells. Inhibition of the matrix metalloproteinase (MMP) family prevents removal of HRS, suggesting an MMP-dependent activation of TGF-β3 in the LDR primed cells. We demonstrate a functional interaction between TGF-β3 and activin receptor like kinase 1 (ALK1) by showing that TGF-β3 removes HRS through ALK1 binding, independent of ALK5 and TGF-βRII. These results are an important contribution to a more comprehensive understanding of the mechanism behind TGF-β3 mediated removal of HRS.     

Cross-linking of amidated low-methoxylated pectin with calcium during extrusion/spheronisation: Effect on particle size and shape

Granulation and pelletisation by wet extrusion/spheronisation is a well-known technique for particle design in the pharmaceutical industry. The objective of this study was to evaluate the use of amidated low-methoxylated (LM) pectin as an excipient for pelletisation by extrusion/spheronisation. The influence of degree of amidation of pectin (14%, 18% and 24%) and concentration of added calcium ions (0%, 5%, 12% w/w) on the shape and size of pectin pellets was investigated. The chosen approach was to aim at cross-linking during processing which could be obtained by adding calcium ions to the amidated pectin in the powder mixture and perform granulation/extrusion with water. Addition of calcium ions was expected to reduce the solubility and swelling of pectin during processing, and, consequently, the roundness of the pectin pellets should be improved. Both the degree of amidation and the concentration of added calcium ions as well as the interaction between the two were identified as significant factors in preparation of spherical pellets. The results suggest that the egg-box model alone cannot describe the cross-linking between amidated LM pectin and calcium ions, and it is proposed that the amid group itself plays an important role in the system.     

Amount of characteristic compounds in 15 cultivars of onion (Allium cepa L.) in controlled field trials

BACKGROUND: In order to develop the production of sweet onions (Allium cepa L.) and onions with a high content of flavonols and fibre in Norway, it was necessary to evaluate available cultivars with respect to their content of selected chemical compounds. A field trial with 15 different cultivars was conducted at Landvik in southern Norway. Compounds that reflect onion pungency and sweetness (pyruvate, sugars) and parameters known to have a beneficial impact on health (fructo‐oligosaccharides (FOS), flavonols, antioxidant capacity) were analysed. RESULTS: The sweetest onions with respect to low content of pyruvate and high amount of fructose and glucose ranged in pyruvate content from 2.7 to 3.6 µmol mL^?1. These cultivars were juicy and contained low amounts of FOS and total flavonols. The most pungent onions contained the highest amounts of FOS among the cultivars: 4.53, 3.80 and 5.81 g per 100 g fresh weight (FW) respectively. They also had a high content of flavonols (86.6, 159.2 and 97.6 mg per 100 g FW) and high dry weight content (14.6, 13.5 and 15.6 g per 100 g). CONCLUSION: The sweetest onion cultivars were found to be ‘NUN 9746’, ‘Musica’, ‘Domenica Supersweet’, ‘Colossus’ and ‘Cronus’. The most pungent cultivars were ‘Powell Brown’ and ‘Tilbury’, which also contained the highest amounts of flavonols and gave the highest Trolox equivalent antioxidant capacity (TEAC) values among the 15 cultivars. Copyright © 2007 Society of Chemical Industry