On the Impact of Multiobjective Scalarizing Functions

Recently, there has been a renewed interest in decomposition-based approaches for evolutionary multiobjective optimization. However, the impact of the choice of the underlying scalarizing function(s) is still far from being well understood. In this paper, we investigate the behavior of different scalarizing functions and their parameters. We thereby abstract firstly from any specific algorithm and only consider the difficulty of the single scalarized problems in terms of the search ability of a (1+lambda)-EA on biobjective NK-landscapes. Secondly, combining the outcomes of independent single-objective runs allows for more general statements on set-based performance measures. Finally, we investigate the correlation between the opening angle of the scalarizing function's underlying contour lines and the position of the final solution in the objective space. Our analysis is of fundamental nature and sheds more light on the key characteristics of multiobjective scalarizing functions.Comment: appears in Parallel Problem Solving from Nature - PPSN XIII, Ljubljana : Slovenia (2014

The molecular size continuum of soil organic phosphorus and its chemical associations

The chemical nature of most organic P (Porg) in soil remains ‘unresolved’ but is accounted for by a broad signal in the phosphomonoester region of solution 31P nuclear magnetic resonance (NMR) spectra. The molecular size range of this broad NMR signal and its molecular structure remain unclear. The aim of this study was to elucidate the chemical nature of Porg with increasing molecular size in soil extracts combining size exclusion chromatography (SEC) with solution 31P NMR spectroscopy. Gel-filtration SEC was carried out on NaOH-EDTA extracts of four soils (range 238-1135 mg Porg/kgsoil) to collect fractions with molecular sizes of 70 kDa. These were then analysed by NMR spectroscopy. Organic P was detected across the entire molecular size continuum from 70 kDa. Concentrations of Porg in the >10kDa fraction ranged from 107 to 427 mg P/kgsoil and exhibited on average three to four broad signals in the phosphomonoester region of NMR spectra. These broad signals were most prominent in the 10-20 and 20-50 kDa fractions, accounting for on average 77 % and 74 % of total phosphomonoesters, respectively. Our study demonstrates that the broad signal is present in all investigated molecular size fractions and comprises on average three to four components of varying NMR peak line width (20 to 250 Hz). The stereoisomers myo- and scyllo-inositol hexakisphosphates (IP6) were also present across multiple molecular size ranges but were predominant in the 5-10 kDa fraction. The proportion of IP associated with large molecular size fractions >10 kDa was on average 23 % (SD=39 %) of total IP across all soils. These findings suggest that stabilisation of IP in soil includes processes associated with the organic phase

Phosphorus species in sequentially extracted soil organic matter fractions

The majority of organic P (Porg) in soil is considered to be part of soil organic matter (SOM) associations, but its chemical nature is largely ‘unresolved’. In this study, we investigated the Porg composition in different SOM fractions of a Gleysol soil using the Humeomics sequential chemical fractionation (SCF) procedure combined with nuclear magnetic resonance (NMR) spectroscopy. In summary, SCF procedure with subsequent NaOH-EDTA extraction of the soil residue extracted a total of 1769 mg P/kgsoil compared to 1682 mg P/kgsoil of a single-step NaOH-EDTA extraction. Approximately 38 % of the extracted Porg was present in the form of the unresolved Porg pool, which was represented by one or two underlying broad signals in the phosphomonoester region of solution 31P NMR spectra. The SCF revealed that phosphomonoesters were recovered in each fraction: 47 % of the unresolved phosphomonoesters were associated with the SOM fraction released by breaking ester bonds (40 %) and ether bonds (7 %), whereas about 30 % of this unresolved Porg pool appeared in the SOM fraction closely associated with the soil mineral phase. Furthermore, the extractability of inositol phosphates (IP) was increased from 312 mg P/kgsoil to 534 mg P/kgsoil (factor 1.7) using the SCF procedure compared to a single-step NaOH-EDTA extraction. Previous studies have reported the presence of IP in molecular size fractions greater than 10 kDa. Our findings on the removal of IP with the fractionation of the SOM could explain the presence of IP in these large associations. We demonstrate that major pools of Porg are closely associated with SOM structures, comprising a diverse array of chemical species and bonding types. These results forward our understanding of Porg stabilisation, P transformation, and P cycling in terrestrial ecosystems towards an association point of view

124I-L19-SIP for immuno-PET imaging of tumour vasculature and guidance of 131I-L19-SIP radioimmunotherapy

Purpose: The human monoclonal antibody (MAb) fragment L19-SIP is directed against extra domain B (ED-B) of fibronectin, a marker of tumour angiogenesis. A clinical radioimmunotherapy (RIT) trial with 131 I-L19-SIP was recently started. In the present study, after GMP production of 124 I and efficient production of 124 I-L19-SIP, we aimed to demonstrate the suitability of 124 I-L19-SIP immuno-PET for imaging of angiogenesis at early-stage tumour development and as a scouting procedure prior to clinical 131 I-L19-SIP RIT. Methods: 124 I was produced in a GMP compliant way via 124 Te(p,n) 124 I reaction and using a TERIMO™ module for radioiodine separation. L19-SIP was radioiodinated by using a modified version of the IODO-GEN method. The biodistribution of coinjected 124 I- and 131 I-L19-SIP was compared in FaDu xenograft-bearing nude mice, while 124 I PET images were obtained from mice with tumours of 90%, respectively. Tumour uptake was 7.3±2.1, 10.8±1.5, 7.8±1.4, 5.3±0.6 and 3.1±0.4%ID/g at 3, 6, 24, 48 and 72 h p.i., resulting in increased tumour to blood ratios ranging from 6.0 at 24 h to 45.9 at 72 h p.i.. Fully concordant labelling and biodistribu- tion results were obtained with 124 I- and 131 I-L19-SIP. Immuno-PET with 124 I-L19-SIP using a high-resolution research tomograph PET scanner revealed clear delineation of the tumours as small as 50 mm3 and no adverse uptake in other organs. Conclusions: 124 I-MAb conjugates for clinical immuno-PET can be efficiently produced. Immuno-PET with 124 I-L19-SIP appeared qualified for sensitive imaging of tumour neo- vasculature and for predicting 131 I-L19-SIP biodistribution.ISSN:1619-7070ISSN:1619-708

Behavior and Impact of Zirconium in the Soil–Plant System: Plant Uptake and Phytotoxicity

Because of the large number of sites they pollute, toxic metals that contaminate terrestrial ecosystems are increasingly of environmental and sanitary concern (Uzu et al. 2010, 2011; Shahid et al. 2011a, b, 2012a). Among such metals is zirconium (Zr), which has the atomic number 40 and is a transition metal that resembles titanium in physical and chemical properties (Zaccone et al. 2008). Zr is widely used in many chemical industry processes and in nuclear reactors (Sandoval et al. 2011; Kamal et al. 2011), owing to its useful properties like hardness, corrosion-resistance and permeable to neutrons (Mushtaq 2012). Hence, the recent increased use of Zr by industry, and the occurrence of the Chernobyl and Fukashima catastrophe have enhanced environmental levels in soil and waters (Yirchenko and Agapkina 1993; Mosulishvili et al. 1994 ; Kruglov et al. 1996)

An affinity matured minibody for PET imaging of prostate stem cell antigen (PSCA)-expressing tumors

PurposeProstate stem cell antigen (PSCA), a cell surface glycoprotein expressed in normal human prostate and bladder, is over-expressed in the majority of localized prostate cancer and most bone metastases. We have previously shown that the hu1G8 minibody, a humanized anti-PSCA antibody fragment (single-chain Fv-C(H)3 dimer, 80 kDa), can localize specifically and image PSCA-expressing xenografts at 21 h post-injection. However, the humanization and antibody fragment reformatting decreased its apparent affinity. Here, we sought to evaluate PET imaging contrast with affinity matured minibodies.MethodsYeast scFv display, involving four rounds of selection, was used to generate the three affinity matured antibody fragments (A2, A11, and C5) that were reformatted into minibodies. These three affinity matured anti-PSCA minibodies were characterized in vitro, and following radiolabeling with (124)I were evaluated in vivo for microPET imaging of PSCA-expressing tumors.ResultsThe A2, A11, and C5 minibody variants all demonstrated improved affinity compared to the parental (P) minibody and were ranked as follows: A2 > A11 > C5 > P. The (124)I-labeled A11 minibody demonstrated higher immunoreactivity than the parental minibody and also achieved the best microPET imaging contrast in two xenograft models, LAPC-9 (prostate cancer) and Capan-1 (pancreatic cancer), when evaluated in vivo.ConclusionOf the affinity variant minibodies tested, the A11 minibody that ranked second in affinity was selected as the best immunoPET tracer to image PSCA-expressing xenografts. This candidate is currently under development for evaluation in a pilot clinical imaging study

Inert coupling of IRDye800CW to monoclonal antibodies for clinical optical imaging of tumor targets

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas