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Carbon nanotubes (CNT) supported (10 wt.%) nickel catalysts were evaluated for the hydrogenation of levulinic acid (LA) to γ-valerolactone (GVL) using a trickle-bed reactor at 180 °C and 30 bar. The effect of nature of the nickel precursors salts (NiNIT- Ni(NO3)2.6H2O, NiACET- Ni(CH3COO)2.4H2O) and NiHYD- Ni(OH)2) and the preparation method on the distribution of Ni particles inside (CNTIN) and outside (CNTOUT) of the carbon nanotubes were investigated. The nickel catalysts were synthesized by incipient wetness impregnation method without opening or functionalization of CNTs. The difference between the preparation of Ni/CNTIN and Ni/CNTOUT catalysts was the pre-filling of the pores of the CNT with p-xylene before the impregnation of the nickel salts for the Ni/CNTOUT samples. These methodologies led to the complete deposition of Ni particles outside of pores for Ni/CNTOUT samples, but partial deposition of Ni particles inside of CNTs for Ni/CNTIN samples, regardless of the nickel precursor salt. It was estimated by TEM only 30 % of Ni particles inside CNTs for NiNIT/CNTIN. The Ni/CNTOUT catalysts prepared from nickel nitrate and nickel hydroxide salts showed the highest activity for LA hydrogenation, compared to those prepared from nickel acetate salts, which is likely due to the higher metal dispersion.

Aim To evaluate biological control agents (BCAs) against Fusarium graminearum on infected maize stalks as a means to reduce Fusarium head blight (FHB) in subsequently grown wheat. Methods and Results In the laboratory, BCAs were applied against F. graminearum on maize stalk pieces. Clonostachys rosea inhibited the perithecia development and ascospore discharge when applied before, simultaneously with and after the pathogen. In the field, we simulated a system with high disease pressure, that is, a maize‐wheat rotation under no‐tillage, by preparing maize stalks inoculated with F. graminearum. The infected stalks were treated with formulations of C. rosea selected in vitro or the commercial BCA strain Trichoderma atrobrunneum ITEM908 and exposed to field conditions over winter and spring between winter wheat rows. Monitoring with spore traps and of FHB symptoms, as well as quantification of F. graminearum incidence and DNA in harvested grain revealed significant reductions by C. rosea by up to 85, 91, 69 and 95% compared with an inoculated but untreated positive control, respectively. Deoxynivalenol (DON) and zearalenone (ZEN) contents were reduced by up to 93 and 98%, respectively. Treatments with T. atrobrunneum were inconsistent, with significant reductions of DON and ZEN under warm and wet climatic conditions only. Conclusions The findings support the application of C. rosea against F. graminearum on residues of maize to suppress the primary inoculum of FHB. Significance and Impact of the Study As sustainable agriculture requires solutions to control FHB, hence, the application of C. rosea during the mulching of maize crop residues should be evaluated in on‐farm experiments. ISSN:1364-5072 ISSN:1365-2672

Over an eight-year period, 686 winter wheat grain samples and information on their cropping history were obtained from Swiss growers. To estimate the risk of Fusarium head blight (FHB), grains were examined for Fusarium species incidence, mycotoxin content as well as the abundance of F. graminearum (FG) and F. poae (FP) DNA and three chemotypes, 15-acetyl-deoxynivalenol (15ADON), 3-acetyl-deoxynivalenol (3ADON) and nivalenol (NIV). Of all Fusarium species, FG and FP were predominant, and the average abundance of the FG DNA was three times higher compared with that of FP. The average detection of the 15ADON chemotype was twice as high as those of 3ADON and NIV, respectively. Deoxynivalenol (DON), zearalenone (ZEA) and nivalenol (NIV) were the most frequently detected toxins. For DON, 11% and for ZEA, 7% of all samples exceeded the European maximum limits for unprocessed cereals intended for human consumption. Furthermore, NIV was most likely produced by four different Fusarium species. A multiple correspondence analysis revealed that high levels of FG and DON were mainly observed in grain samples from fields with the previous crop maize, reduced tillage, cultivars with poor FHB resistance and strobilurin-based fungicides. Other previous crops and/or ploughing decreased the DON content by 78 to 95%. ZEA showed a similar pattern. In contrast, high levels of FP and NIV were associated with samples from ploughed fields and the previous crop canola. These findings and the negative correlations between FP DNA and FG incidence, ZEA and DON suggest a different ecological niche for FP or diverging requirements for growth and infection.

Ti interstitials are key actors in the reduction/re-oxidation processes of TiO2. The charge redistribution originated by these point defects is acknowledged to trigger the dissociation of small molecules at the surface, while the direct involvement of Ti interstitials in reactions with adsorbates is an open question. From a combined experimental and theoretical investigation, we show how the potential energy surface for the outdiffusion of Ti interstitials at rutile-TiO2(1 1 0) is strongly lowered by adsorbed porphyrins, independently of their peripheral terminations. The process is activated by a nucleophilic attack of an iminic N to a surface 6-fold coordinated Ti atom, which is sequestrated by the porphyrin and replaced by a subsurface interstitial. From comparison with acidic porphyrins, we show that Ti extraction is specifically driven by the Lewis basicity of iminic N, which opens the pathway to the chemical reaction of Ti interstitials with a larger class of molecular systems., C.R. acknowledges funding from the Spanish Ministry of Economy and Competitiveness (grant MAT2016–78293–C6–5–R [AEI/ERDF, EU]) and from the Basque Government (grant IT–1255–19). L.F. acknowledges funding's from the Italian Ministry of Research and University through EUROFEL project.

Appealing physical and chemical properties are foreseen in nanoparticles containing immiscible elements, despite their synthesis is challenging due to the unfavorable thermodynamics. Here we show that silver nanoparticles doped with Co can be achieved by a facile one-step route relying on laser ablation in liquid. Structural analysis suggests that the bimetallic nanoparticles consist of a matrix of face-centred cubic Ag rich of cobalt as point defects or dislocations, in a structure that is stable over time even in aqueous solution. This happens despite the complete immiscibility of the two metals at any temperature in the solid and liquid phase, as confirmed also by density functional theory calculations. The nonequilibrium Co-Ag nanoparticles benefit of silver features such as the plasmonic response and the easy surface chemistry with thiolated ligands, combined with the magnetic properties of cobalt. Importantly, plasmonics and magnetism are not quenched after mixing, contrary to what was observed in other bimetallic systems like the Au-Fe one. This opens the way to several technologically relevant applications and, as a proof of concept, we demonstrate magnetophoretic assembly of Co-Ag nanoparticles into arrays of plasmonic dots exploitable for surface-enhanced Raman spectroscopy.

Seckel syndrome is a type of microcephalic primordial dwarfism (MPD) that is characterized by growth retardation and neurodevelopmental defects, including reports of retinopathy. Mutations in key mediators of the replication stress response, the mutually dependent partners ATR and ATRIP, are among the known causes of Seckel syndrome. However, it remains unclear how their deficiency disrupts the development and function of the central nervous system (CNS). Here, we investigated the cellular and molecular consequences of ATRIP deficiency in different cell populations of the developing murine neural retina. We discovered that conditional inactivation of Atrip in photoreceptor neurons did not affect their survival or function. In contrast, Atrip deficiency in retinal progenitor cells (RPCs) led to severe lamination defects followed by secondary photoreceptor degeneration and loss of vision. Furthermore, we showed that RPCs lacking functional ATRIP exhibited higher levels of replicative stress and accumulated endogenous DNA damage that was accompanied by stabilization of TRP53. Notably, inactivation of Trp53 prevented apoptosis of Atrip-deficient progenitor cells and was sufficient to rescue retinal dysplasia, neurodegeneration and loss of vision. Together, these results reveal an essential role of ATRIP-mediated replication stress response in CNS development and suggest that the TRP53-mediated apoptosis of progenitor cells might contribute to retinal malformations in Seckel syndrome and other MPD disorders. This article has an associated First Person interview with the first author of the paper., Summary: Retinopathies have been reported in primordial dwarfism syndromes. We show that the loss of Atrip, a gene mutated in Seckel syndrome, causes photoreceptor degeneration owing to p53-dependent apoptosis of retinal progenitors during development.

Fusarium graminearum is a phytopathogenic fungus that causes Fusarium head blight in small-grain cereals, such as wheat, with significant yield reductions. Moreover, it contaminates the cereal grains with health-threatening mycotoxins, such as deoxynivalenol (DON), jeopardizing food and feed safety. Plant-based biopesticides, i.e. botanicals, have recently gained increased interest in crop protection as alternatives to synthetic chemical products. The main objective of this study was to test the control efficacy of botanicals based on white or Indian/Oriental mustard seed flours (Tillecur – Ti, Pure Yellow Mustard – PYM, Pure Oriental Mustard – POM, Oriental Mustard Bran – OMB) on F. graminearum infection and mycotoxin accumulation in wheat grain. Botanicals at 2% concentration showed a higher efficacy in inhibiting mycelium growth in vitro compared with a prothioconazole fungicide (F). In the growth chamber experiment under controlled conditions, the spraying agents reduced DON content in grain in the following order: F = Ti = PYM > POM > OMB. The antifungal activity of the botanicals may be attributed to their bioactive matrices containing isothiocyanates (ITCs) and phenolic acids. Allyl ITC was detected in POM and OMB at 8.38 and 4.48 mg g–1, while p-hydroxybenzyl ITC was found in Ti and PYM at 2.56 and 2.44 mg g–1, respectively. Considerable amounts of various phenolic acids were detected in all botanicals. Under field conditions, only the use of F significantly decreased F. graminearum infection and DON content in grain. An additional important finding of this study is that disease control was more difficult when infection was done with ascospores than conidia, which might have several potential implications considering that ascospores are more important in Fusarium head blight epidemics. Our results suggest that mustard-based botanicals are promising biopesticides for the control of Fusarium head blight in small-grain cereals, but for field applications, an appropriate formulation is necessary to stabilize and prolong the antifungal activity, especially against ascospores. ISSN:1664-302X

Bismuth vanadate (BiVO4) has emerged as one of the most promising photoanode materials for solar fuel production. Oxygen vacancies play a pivotal role in the photoelectrochemical efficiency, yet their electronic nature and contribution to n-type conductivity are still under debate. Using first-principles calculations, we show that oxygen vacancies in BiVO4 have two distinguishable geometric configurations characterized by either undercoordinated, reduced VIVO3 and BiIIO7 subunits or a VIV−O−VIV/V bridge (split vacancy), quenching the oxygen vacancy site. While both configurations have similar energies in the bulk, the (001) subsurface acts like an energetic sink that stabilizes the split oxygen vacancy by ∼1 eV. The barrierless creation of a bridging V2O7 unit allows for partial electron delocalization throughout the near-surface region, consistent with recent experimental observations indicating that BiVO4(001) is an electron-rich surface.

High occurrence of Fusarium poae (FP) and Fusarium langsethiae (FL) and their mycotoxins nivalenol (NIV) and T‐2/HT‐2 have been observed in Swiss oats. Early prediction of mycotoxin levels is important for farmers and the cereal industry to minimize the risk of contaminated food and feed. Therefore, climate chamber experiments were conducted to investigate the influence of different temperatures (10, 15, 20 °C) and durations (4, 8, 12 h) at 99% relative humidity (RH) on the infection of oats with FP and FL. In addition, to discover the most susceptible period of oats, artificial FL inoculations were conducted at different growth stages. Field experiments were performed to observe the dispersal of these fungal species within the field and to investigate the weather conditions that influence the dispersal. The climate chamber experiments revealed higher contamination with NIV and T‐2/HT‐2 in the 10 °C treatments and with a prolonged humidity duration of 12 h 99% RH. Inoculations of oat plants at early (DC 61) and mid (DC 65) anthesis, led to higher FL infection and T‐2/HT‐2 accumulation in the grains compared with treatments at earlier growth stages, which might be due to an increased susceptibility during anthesis. No indication for spore dispersal was observed in the field experiments. The results obtained, together with the cropping factors that influence infection and mycotoxin production, could be used as a first step in developing forecasting models to predict the contamination of oats with the mycotoxins NIV and T‐2/HT‐2.

RATIONALE [Cu(P)4 ][BF4 ]-type complexes (P = tertiary phosphine) have shown significant antitumor activity. This biological property appears to be activated via formation of coordinative unsaturated [Cu(P)n ]+ species (n

A semiempirical addition of dispersive forces to conventional density functionals (DFT-D) has been implemented into a pseudopotential plane-wave code. Test calculations on the benzene dimer reproduced the results obtained by using localized basis set, provided that the latter are corrected for the basis set superposition error. By applying the DFT-D/plane-wave approach a substantial agreement with experiments is found for the structure and energetics of polyethylene and graphite, two typical solids that are badly described by standard local and semilocal density functionals. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009

Fusarium head blight is one of the most noxious cereal diseases. Worldwide, F. graminearum (FG) and the mycotoxin deoxynivalenol (DON) is the most dominant species/mycotoxin in barley and wheat. Barley is often produced as on farm feed and thus routine mycotoxin analyses similar to those of cereals for human consumption are not performed. Hence, an early prediction of mycotoxin levels is important for farmers to minimise the risk of contaminated feed but also of contaminated cereals entering the cereal supply chain. Therefore, climate chamber experiments with artificial FG infection of barley investigating the influence of different temperatures (10 °C, 15 °C, 20 °C) and durations (4 h, 8 h, 12 h) at 99% relative humidity were conducted to accumulate data to develop a forecasting system. An up to three times higher DON contamination in the 15 °C treatments for the feed barley variety Ascona was detected compared with the 10 °C and 20 °C treatments. For the malting barley variety Concerto, the prolonged humidity durations had a stronger effect under all tested temperatures and resulted in up to two times higher DON contaminations. In addition, field experiments where spore deposition during anthesis as well as disease incidence, fungal amount and mycotoxins were observed, showed that the overwintered straw treatment resulted, depending on the year, in a three times higher FG incidence and DON content compared with the control and freshly inoculated straw treatment.

Administration of positively charged amino acids has been introduced to reduce the nephrotoxicity of targeted radiopeptide therapy (TRT). However, the amino acid solution may have side effects, including hyperkalaemia. The aim of this study was to evaluate the frequency and the magnitude of hyperkalaemia in neuroendocrine tumour (NET) patients undergoing TRT.Enrolled in the study were 31 patients with NET eligible for TRT with [(90)Y-DOTA(0),Tyr(3)]octreotide ((90)Y-DOTATOC). Their mean age was 54 ± 14 years. Of these 31 patients, 21 (67%) were referred for the first treatment cycle, while 10 (33%) were referred for a subsequent therapy cycle. Patients were treated with therapeutic doses of (90)Y-DOTATOC ranging from 7,030 to 35,520 MBq. To inhibit tubular reabsorption of (90)Y-DOTATOC, 1 l of physiological saline solution containing 25 g of arginine hydrochloride and 25 g of lysine hydrochloride was given over 4 h starting 1 h before (90)Y-DOTATOC injection. All patients underwent a standard biochemical blood analysis at baseline, and 4 h and 24 h after the beginning of the amino acid infusion.ANOVA repeated measures showed a significant overall effect on K(+) levels over time (F = 118.2, df = 2, P0.0001). Mean serum levels of K(+) were 4.00 ± 0.33 mmol/l at baseline, 5.47 ± 0.57 mmol/l at 4 h, and 4.38 ± 0.63 mmol/l at 24 h after the beginning of the infusion. Post-hoc analysis showed that K(+) levels at 4 h were significantly (P0.05) higher than at baseline. K(+) levels at 24 h were significantly (P0.05) lower than at 4 h but they were still significantly (P0.05) higher than K(+) levels at baseline. On a subject-by-subject basis, none of the 31 patients had increased K(+) levels at baseline. At 4 h, 24 of the 31 patients (77%) had K(+) levels above the normal range, and 6 patients (19%) experienced severe hyperkalaemia (K(+) ≥ 6 mmol/l). All patients with increased K(+) levels were clinically asymptomatic. At 24 h, only 4 patients (13%) had increased K(+) serum levels. The magnitude of the increase in K(+) levels between baseline and 4 h was relatively homogeneous over the whole group (1.41 ± 0.50 mmol/l) and it was not related (linear regression, P0.05) to baseline K(+) levels. Intravenous administration of 40 mg furosemide 1 h after the beginning of the amino acid infusion did not have a significant effect on K(+) levels (P0.05). No clinical characteristic was predictive for the increase in K(+) levels (chi-squared test, P0.05).Hyperkalaemia is a frequent, potentially life-threatening side effect of basic amino acid infusion during TRT. K(+) levels 4 h after the beginning of the infusion should be monitored in patients at risk of complications, such as those with heart disease and those with risk factors for nephrotoxicity.

The reference ranges of the trace elements Al, As, Be, B, Cd, Co, Cu, Fe, Mn, Mo, Ni, Pb, Li, Rb, Se, Sr, and Zn were determined by inductively coupled plasma-mass spectrometry (ICP-MS) in sera of a group of free-ranging plains viscachas of the pampa grasslands of Argentina. The values were compared with those of a small group of captive plains viscachas of the Zurich Zoo with diabetes and bilateral cataracts. In addition, a method for digestion of whole-blood samples is described for the trace element determination. Significant differences in the concentration of trace elements in the two groups of animals are discussed. No correlation was found between the levels of selenium and of other trace elements compared to the formation of cataracts.

The purification of therapeutic peptides is most often performed using one or more reversed phase chromatography steps. This ensures high purities while keeping the costs of purification under control. In this paper, a doped reversed phase chromatographic material is tested and compared to traditional reversed phase materials. The doping consists of adding limited amounts of ion exchange ligands to the surface of the material to achieve orthogonal separation and increase the non-hydrophobic interactions with the surface. These ionic groups can either be attractive (opposite charge), or repulsive (same charge) to the peptide. The benefit of this new doped reversed phase material is shown through increases in selectivity in diluted conditions and yield and productivity in overloaded (i.e. industrial) conditions. It is the conjectured that all performance characteristics should increase using repulsive doping groups, whereas these characteristics should decrease when using attractive doping groups. This conjecture is shown to be true through several examples, including purifications of industrially relevant peptide crudes, in industrially relevant conditions. Moreover, the effect of ionic strength and organic modifier concentration was explored and shown to be in line with the expected behavior.

The consequences of the evolution of the active site in the oxygen reduction reaction catalyzed by iron phthalocyanine (FePc) submonolayers deposited on the Ag(110) surface are explored. The capacity of reversibly and sharply switching the magnetic state of FePc molecules by chemical means is conclusively evidenced by X-ray magnetic circular dichroism (XMCD) at the Fe L2,3 absorption edge. In the molecular oxygen-dosed phase, oxygen intercalates between the molecule and the surface, thereby switching the Fe magnetic moment from a nearly negligible (mTotexp ≈ 0.26(1) μB) to an order of magnitude larger value (mTotexp ≈ 2.1(2) μB). Moreover, the characteristic XMCD spectrum undergoes a crossover from metallic to oxidized Fe(III)-like line shape, in accordance with an oxygen-induced decoupling of the molecular electronic states from the underlying metal surface. The FePc acts as a reversible bifunctional chemical–magnetic switch at the atomic monolayer scale., Financial support from the projects MINECO MAT2011/23791, MAT2014-53921-R, and DGA IMANA E34, as well as MIUR project PRIN 2010BNZ3F2 “DESCARTES” and Progetti di Ricerca di Ateneo, (CPDA118475/11) are acknowledged here.

A theoretical study of the adsorption and dynamics of tetraphenylporphyrins on a Ag(111) substrate and the subsequent aggregation of the formed monolayers with fullerene molecules is reported. Classical molecular dynamics simulations were able to reveal the various phases of monolayer and bilayer formation and succeeded in identifying all the interactions responsible for self-assembling and surface binding. Possible supramolecular configurations extracted from the molecular dynamics trajectories were classified and characterized in detail and revealed to be in satisfactory agreement with experimental data.

We demonstrate the thermal stability up to 450 °C of a titanium(iv)-porphyrin monolayer grown on the rutile TiO(110) surface. Starting from a film of metal-free tetra-phenyl-porphyrin, 2HTPP, deposited at room temperature, we show that, beyond the self-metalation reaction at 150°-200 °C, a second phase transition takes place at ∼350 °C. Using surface diffraction and microscopy, we observe a change of the phase symmetry from (2 × 4)-obliq to (2 × 6)-rect. Core level photoemission indicates that the chemical states of both the molecular tetrapyrrolic macrocycle and the substrate are unchanged. X-ray absorption spectroscopy reveals that the driving mechanism is a rotation of the phenyl terminations towards the substrate (flattening) that triggers a conformational change of the molecule through partial cyclo-dehydrogenation. From comparison with first principles calculations, we show that the common feature of these multiple phase transitions is the chemical nature of the porphyrin bonding atop the substrate oxygen rows: the coordination of the macrocycle central pocket to the oxygen atoms beneath is preserved throughout both the self-metalation and flattening reactions. The molecular orientation and arrangement are determined by steric constraints and intermolecular interactions, whereas the specific adsorption site is further stabilized by the interaction of the peripheral C-H network with the adjacent oxygen rows. Porphyrins are thus trapped at the TiO(110) surface, where they demonstrate an exceptionally high thermal stability (up to ∼450 °C), which makes this interface potentially useful for sensors and photocatalysis applications in harsh environments., We acknowledge the support from the MIUR of Italy through PRIN project DESCARTES (no. 2010BNZ3F2), from the Spanish Government (Grant MAT2013-46593-C6-4-P) and from the Basque Department of Education (Grant IT-621-13). M. A. also acknowledges the financial support of DIPC.

In this work, we show the possibility of tailoring the molecular arrangement, as well as chemical and structural modifications, of porphyrins at monolayer saturation coverage on TiO(110) by synchrotron photoemission spectroscopy, electron diffraction, STM topography, and DFT calculations. Free-base tetraphenylporphyrins (2H-TPP) adsorb on the oxygen rows, where they can spontaneously capture two additional hydrogen atoms at their iminic nitrogens (4H-TPP). Both 2H-TPP and 4H-TPP molecules aggregate into a commensurate phase at the saturation coverage of 1 ML. Upon sample heating, a self-metalation reaction sets in at 100 °C, yielding full metalation of the saturated monolayer at ∼200 °C. The Ti atoms are extracted from the substrate and, by simultaneous dehydrogenation of the pyrrolic nitrogen atoms, incorporated into the porphyrin macrocycle, where they remain coordinated to two underlying oxygen atoms. Neither the adsorption geometry (on-bridge, atop the oxygen rows) nor the molecular arrangement changes across the self-metalation transition up to 300 °C. On one hand, the robustness of this saturation phase makes it a promising system for implementation in applications for photocatalysis and photovoltaic devices. On the other hand, the possible manifestation of metal exchange with the very reactive Ti atoms must be taken into account when designing porphyrin-sensitized solar cells because the critical temperature for the onset of self-metalation is very close to the normal operating temperature of photovoltaic devices., We acknowledge support from the MIUR of Italy through PRIN Project DESCARTES (no. 2010BNZ3F2), from the Spanish Government (Grant MAT2013-46593-C6-4-P), and from the Basque Department of Education (Grant IT-621-13). M.A. also acknowledges the financial support of MPC.

Suspensions or solutions with 1% of Chinese galls (Galla chinensis, GC) or 1% of tannic acid (TA), inhibited germination of conidia or mycelium growth of Fusarium graminearum (FG) by 98%–100% or by 75%–80%, respectively, whereas dried bark from buckthorn (Frangula alnus, FA) showed no effect at this concentration. In climate chamber experiments where the wheat variety “Apogee” was artificially inoculated with FG and F. crookwellense (FCr) and treated with 5% suspensions of TA, GC and FA, the deoxynivalenol (DON) content in grains was reduced by 81%, 67% and 33%, respectively. In field experiments with two commercial wheat varieties and artificial or semi-natural inoculations, mean DON reductions of 66% (TA) and 58% (FA), respectively, were obtained. Antifungal toxicity can explain the high efficacies of TA and GC but not those of FA. The Fusarium head blight (FHB) and mycotoxin reducing effect of FA is probably due to elicitation of resistance in wheat plants. With semi-natural inoculation, a single FA application in the first half of the flowering period performed best. However, we assume that applications of FA at the end of ear emergence and a treatment, triggered by an infection period, with TA or GC during flowering, might perform better than synthetic fungicides.

The adsorption of formic acid at smectite edges is investigated by DFT calculations using a model system based on pyrophyllite. Two cases are considered: (I) only the Si atoms are saturated with water molecules and the edges are exposed at the vacuum; (II) all the exposed Al cations are also saturated, and the edges are in equilibrium with an aqueous environment at 298 K. In the former case, adsorption is strong, and involves the formation of monodentate e bidentate species. Most of complexes have a negative formation energy also in wet conditions, which indicates the occurrence of stable aqueous interfaces.

Dodonaea ‘Dana’ is a natural hybrid (Dodonaea viscosa purpurea x Dodonaea aptera) cultivated for the production of decorative cut branches bearing dark red foliage with red fruit. This hybrid flowers throughout the year in the Mediterranean climate, but fruit set occurs only during the winter, leading to a short two month period of fruit bearing branches. The aim of this work was to characterize the environmental conditions affecting fruit set in D. ‘Dana’ plants, and improve the efficiency under sub-optimal conditions by hormonal treatment of the plants. When plants were grown at different temperature regimes the number of fruit developed from each inflorescence was 3-fold higher in plants grown at 17 °C/9 °C, in comparison to 29 °C/21 °C, suggesting that temperature is a critical factor for the development of D. ‘Dana’ fruit. In addition, the anthocyanin concentration of fruit grown at the lower temperature regime was four times higher than those grown at the elevated temperature. To improve fruit setting in plants grown at moderate or elevated temperatures (23 °C/15 °C and 29 °C/21 °C), individual inflorescences were treated with one of the two synthetic auxins, naphthalene-1-acetic acid (NAA) and 4-chlorophenoxy acetic acid (4-CPA). Both auxins increased the number of set fruit per inflorescence at both temperature regimes, with an advantage to the NAA treatment at the 23 °C/15 °C regime. Treatment of whole plants with either NAA or 4-CPA at 26 °C/18 °C (day/night respectively) regime, caused a significant increase (2.5–3-fold) in the number of inflorescences per branch with no visual effect on the vegetative characteristics of the plants. In addition, NAA treatment caused an increase of over 50% in the number of flowers per inflorescence. Similar to the treatment of individual inflorescences, here too both synthetic auxins improved the yield of fruit setting.

Background: We aimed to assess the level of DNA damage and susceptibility to exogenous mutagens in peripheral blood cells of Chronic Obstructive Pulmonary Disease (COPD) patients and healthy individuals by comet assay. Oxidative stress was also evaluated by means of thiobarbituric acid reactive species (TBARS) in blood plasma. Methods: Case-control study enrolling 51 COPD patients and 51 controls. Peripheral blood was used to perform the alkaline (pH>13) and neutral (pH=8.5) comet assay. For the assessment of susceptibility to exogenous DNA damage, the cells were treated with methylmethane sulfonate (MMS) for 1-hour or 3-hour at 37° C. The percentage of residual DNA damage after 3-h MMS treatment was calculated using the value of 1-h MMS treatment for each subject as 100%. Lipid peroxidation was evaluated by measuring TBARS in blood plasma. Results: DNA damage in patients was significantly higher than in controls as measured by the neutral and alkaline comet assay. Residual DNA damage detected after MMS treatment increased in patients, in contrast to controls, indicating higher susceptibility to alkylation damage and/or repair inhibition. High susceptibility to exogenous DNA damage in COPD patients correlates with high amount of TBARS and low forced vital capacity and expiratory volume. Conclusion: The positive correlation between increased susceptibility to exogenous DNA damage and TBARS levels in COPD patients suggests the possible involvement of oxidative stress in damage induction and/or repair inhibition.

Objective To investigate the antimicrobial effect of alpha-bisabolol and tea tree oil alone and in combination against the halitosis-associated Gram-positive bacillus Solobacterium moorei. Design The inhibitory activity of alpha-bisabolol and tea tree oil against the reference strain S. moorei CCUG39336 and four clinical S. moorei isolates was investigated by a direct exposure test. Additionally, the ability of alpha-bisabolol to increase the sensitivity of S. moorei was tested by pretreating the bacteria with sublethal concentrations prior to the administration of tea tree oil. Results A dose-dependent killing was observed for the antimicrobial agents in a direct exposure test with the reference strain S. moorei CCUG39336. Concentrations of ≥0.5% tea tree oil caused decreases in viability of >5 log colony forming units/ml even after short incubation periods, while bacterial viability was less affected by alpha-bisabolol. The combination of 0.1% alpha-bisabolol plus 0.05% tea tree oil showed a synergistic effect on S. moorei strain CCUG39336 and on two of the four clinical S. moorei isolates tested. However, incubation of S. moorei with a sublethal concentration of 0.1% alpha-bisabolol for three days prior to the administration of 0.05% tea tree oil did not enhance the antibacterial effect of tea tree oil. Conclusion Halitosis-associated bacterium S. moorei is susceptible to the antimicrobial agents tea tree oil and alpha-bisabolol, suggesting that these compounds might be beneficial in oral healthcare products.

A long systemic half-life is key for therapeutic proteins. To that end we have generated serum albumin-binding designed ankyrin repeat domains. These domains bind serum albumin of different species with nanomolar affinities, and have significantly improved pharmacokinetic properties both in mouse and cynomolgus monkey compared to non-serum albumin-binding DARPin® domains. In addition, they exhibit high thermal stability and long storage stability, which is an essential feature for their use in drug development. Covalently linking a serum albumin-binding DARPin® domain to domains with other target specificities results in improvements of multiple orders of magnitude in exposure and terminal half-life, both in mouse and cynomolgus monkey. Pharmacokinetic assessment of such constructs revealed terminal half-life values ranging from 27 h to 80 h in mouse, and from 2.6 days to 20 days in cynomolgus monkey. Extrapolation by allometric scaling on these findings suggests terminal half-life values of 5-50 days in human, indicating that pharmacokinetic properties in the range of monoclonal antibodies can be achieved with DARPin® drug candidates. Such serum albumin-binding DARPin® domains are thus valuable tools for the generation of multi-functional drugs with an extended in vivo half-life.

Host control of infections crucially depends on the capability to kill pathogens with reactive oxygen species (ROS). However, these toxic molecules can also readily damage host components and cause severe immunopathology. Here, we show that neutrophils use their most abundant granule protein, myeloperoxidase, to target ROS specifically to pathogens while minimizing collateral tissue damage. A computational model predicted that myeloperoxidase efficiently scavenges diffusible H2O2 at the surface of phagosomal Salmonella and converts it into highly reactive HOCl (bleach), which rapidly damages biomolecules within a radius of less than 0.1 μm. Myeloperoxidase-deficient neutrophils were predicted to accumulate large quantities of H2O2 that still effectively kill Salmonella, but most H2O2 would leak from the phagosome. Salmonella stimulation of neutrophils from normal and myeloperoxidase-deficient human donors experimentally confirmed an inverse relationship between myeloperoxidase activity and extracellular H2O2 release. Myeloperoxidase-deficient mice infected with Salmonella had elevated hydrogen peroxide tissue levels and exacerbated oxidative damage of host lipids and DNA, despite almost normal Salmonella control. These data show that myeloperoxidase has a major function in mitigating collateral tissue damage during antimicrobial oxidative bursts, by converting diffusible long-lived H2O2 into highly reactive, microbicidal and locally confined HOCl at pathogen surfaces.

Nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. Diagnosis is often challenging and therapeutic options are scarce.In 2009, a 46-year-old female patient presented with recurrent severe hypoglycemia and immediate recovery after glucose ingestion. Although 72-h-fasting test was positive, various imaging technologies (sonography, computed tomography, somatostatin receptor scintigraphy, dopamine receptor positron emission tomography [DOPA-PET]) were negative. Endoscopic ultrasound revealed a lesion in the pancreatic corpus, whereas selective arterial calcium stimulation test, portal venous sampling and GLP-1-receptor scintigraphy were indicative of a lesion in the pancreatic tail, which was surgically removed. The histopathologic examination revealed beta cell hyperplasia and microadenomas expressing glucagon. After surgery, the patient was free of symptoms for 6 months, after which hypoglycemic episodes recurred. After unsuccessful treatment with corticosteroids and somatostatin analogs, treatment with pasireotide, a novel somatostatin analog with high affinity to somatostatin receptor 5 and a possible side effect of hyperglycemia, was initiated (0.6 mg BID). To date, our patient has been free of severe hypoglycemic episodes ever since. Yearly repeated imaging procedures have shown no abnormities over the last 3 years.We report for the first time that pasireotide was successfully used in the treatment of adult nesidioblastosis.

Mycotoxins are secondary metabolites that are naturally produced by fungi which infest and contaminate agricultural crops and commodities (e.g., small grain cereals, fruits, vegetables, and organic soil material). Although these compounds have extensively been studied in food and feed, only little is known about their environmental fate. Therefore, we investigated over nearly two years the occurrence of various mycotoxins in a field cropped with winter wheat of the variety Levis, which was artificially inoculated with Fusarium spp., as well as their emission via drainage water. Mycotoxins were regularly quantified in whole wheat plants (0.1-133 mg/kg(dry weight), for deoxynivalenol), and drainage water samples (0.8 ng/L to 1.14 μg/L, for deoxynivalenol). From the mycotoxins quantified in wheat (3-acetyl-deoxynivalenol, deoxynivalenol, fusarenone-X, nivalenol, HT-2 toxin, T-2 toxin, beauvericin, and zearalenone), only the more hydrophilic ones or those prevailing at high concentrations were detected in drainage water. Of the total amounts produced in wheat plants (min: 2.3; max: 292 g/ha/y), 0.5-354 mg/ha/y, i.e. 0.002-0.12%, were emitted via drainage water. Hence, these compounds add to the complex mixture of natural and anthropogenic micropollutants particularly in small rural water bodies, receiving mainly runoff from agricultural areas.

Mycotoxins are known to affect the health of humans and husbandry animals. In contrast to wheat grains used for food and feed, whole wheat plants are rarely analysed for mycotoxins, although contaminated straw could additionally expose animals to these toxic compounds. Since the entire wheat plant may also act as source of mycotoxins emitted into the environment, an analytical method was developed, optimised and validated for the analysis of 28 different mycotoxins in above-ground material from whole wheat plants. The method comprises solid-liquid extraction and a clean-up step using a Varian Bond Elut Mycotoxin(®) cartridge, followed by liquid chromatography with electrospray ionisation and triple quadrupole mass spectrometry. Total method recoveries for 26 out of 28 compounds were between 69 and 122% and showed limits of detection from 1 to 26 ng/gdry weight (dw). The overall repeatability for all validated compounds was on average 7%, and their mean ion suppression 65%. Those rather high matrix effects made it necessary to use matrix-matched calibrations to quantify mycotoxins within whole wheat plants. The applicability of this method is illustrated with data from a winter wheat test field to examine the risks of environmental contamination by toxins following artificial inoculation separately with four different Fusarium species. The selected data originate from samples of a part of the field which was inoculated with Fusarium crookwellense. In the wheat samples, various trichothecenes (3-acetyl-deoxynivalenol, deoxynivalenol, diacetoxyscirpenol, fusarenone-X, nivalenol, HT-2 toxin, and T-2 toxin) as well as beauvericin and zearalenone were identified with concentrations ranging from 32 ng/gdw to 12 × 10(3) ng/gdw.

In the present contribution, a series of four metal dithiocarbamates, namely 1-pyrrolidinecarbodithioate methyl ester (PyDTM) of Pd(II) and Pt(II), PtCl2(PyDTM), PtBr2(PyDTM), PdBr2(PyDTM), PdCl2(PyDTM), were analysed by x-ray Photoelectron Spectroscopy (XPS). Besides the wide scan spectra, detailed spectra for the C 1s, O 1s, N 1s, S 2s, S 2p, Pt 4f (for Pt-based compounds), Pd 3d (for Pd-based compounds), Cl 2p (for Cl containing compounds), Br 3p (for Br containing compounds) regions were acquired and the related data are presented and discussed. VC 2011 American Vacuum Society. [http://dx.doi.org/10.1116/11.20091201] Keywords:dithiocarbamates; coordination compounds; metal-sulphur bond; platinum; palladium; sulphur

Bombesin receptors are overexpressed on a variety of human tumors. In particular, the gastrin-releasing peptide receptor (GRPr) has been identified on prostate and breast cancers and on gastrointestinal stromal tumors. The current study aims at developing clinically translatable bombesin antagonist-based radioligands for SPECT and PET of GRPr-positive tumors.A potent bombesin antagonist (PEG(4)-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH(2) [AR]) was synthesized; conjugated to the chelators DOTA, 6-carboxy-1,4,7,11-tetraazaundecane (N4), 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA), and 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (CB-TE2A); and radiolabeled with (111)In, (99m)Tc, (68)Ga, and (64)Cu, respectively. The radioconjugates were evaluated in vitro and in vivo in PC-3 tumor-bearing nude mice. Antagonist potency was determined by Ca(2+)-flux measurements and immunofluorescence.All the conjugates showed high binding affinity to GRPr (inhibitory concentration of 50% [IC(50)], 2.5-25 nmol/L). The immunofluorescence and Ca(2+)-flux assays confirmed the antagonist properties of the conjugates. Biodistribution revealed high and specific uptake in PC-3 tumor and in GRPr-positive tissues. Tumor uptake of (64)Cu-CB-TE2A-AR (31.02 ± 3.35 percentage injected activity per gram [%IA/g]) was higher than (99m)Tc-N4-AR (24.98 ± 5.22 %IA/g), (111)In-DOTA-AR (10.56 ± 0.70 %IA/g), and (68)Ga-NODAGA-AR (7.11 ± 3.26 %IA/g) at 1 h after injection. Biodistribution at later time points showed high tumor-to-background ratios because of the fast washout of the radioligand from normal organs, compared with tumor. High tumor-to-background ratios were further illustrated by PET and SPECT images of PC-3 tumor-bearing nude mice acquired at 12 h after injection showing high tumor uptake, clear background, and negligible or no radioactivity in the abdomen.The chelators do influence the affinity, antagonistic potency, and pharmacokinetics of the conjugates. The promising preclinical results warrant clinical translation of these probes for SPECT and PET.

Aims: To quantify and to compare the occurrence of Fusarium species in maize kernels and stalk pieces, to analyse mycotoxins in kernels and maize crop residues, to evaluate two approaches to obtain kernel samples and to compare two methods for mycotoxin analyses. Methods and Results: The occurrence of Fusarium species in maize kernels and stalk pieces from a three-year maize hybrid trial and 12 kernel samples from grower’s fields was assessed. Nine to 16 different Fusarium species were detected in maize kernels and stalks. In kernels, F. graminearum, F. verticillioides and F. proliferatum were the most prevalent species whereas in stalks, they were F. equiseti, F. proliferatum and F. verticillioides. In 2006, 68% of the kernel samples exceeded the recommended limit for pig feed for deoxynivalenol (DON) and 42% for zearalenone (ZON), respectively. Similarly, 75% of the samples from grower’s fields exceeded the limits for DON and 50% for ZON. In maize crop residues, toxin concentrations ranged from 2·6 to 15·3 mg kg−1 for DON and from 0·7 to 7·4 mg kg−1 for ZON. Both approaches to obtain maize kernel samples were valid, and a strong correlation between mycotoxin analysis using ELISA and LC-MS/MS was found. Conclusions: The contamination of maize kernels, stalk pieces and remaining crop residues with various mycotoxins could pose a risk not only to animal health but also to the environment. With the hand-picked sample, the entire Fusarium complex can be estimated, whereas combine harvested samples are more representative for the mycotoxin contents in harvested goods. Significance and Impact of the Study: This is the first multi-year study investigating mycotoxin contamination in maize kernels as well as in crop residues. The results indicate a high need to identify cropping factors influencing the infection of maize by Fusarium species to establish recommendations for growers.

Maize is frequently infected by the Fusarium species producing mycotoxins. Numerous investigations have focused on grain maize, but little is known about the Fusarium species in the entire plant used for silage. Furthermore, mycotoxins persist during the ensiling process and thus endanger feed safety. In the current study, we analyzed 20 Swiss silage maize samples from growers' fields for the incidence of Fusarium species and mycotoxins. The species spectrum was analyzed morphologically and mycotoxins were measured by LC-MS/MS. A pre-harvest visual disease rating showed few disease symptoms. In contrast, the infection rate of two-thirds of the harvest samples ranged from 25 to 75% and twelve different Fusarium species were isolated. The prevailing species were F. sporotrichioides, F. verticillioides and F. graminearum. No infection specificity for certain plant parts was observed. The trichothecene deoxynivalenol (DON) was found in each sample (ranging from 780 to 2990 µg kg(-1)). Other toxins detected in descending order were zearalenone, further trichothecenes (nivalenol, HT-2 and T-2 toxin, acetylated DON) and fumonisins. A generalized linear regression model containing the three cropping factors harvest date, pre-precrop and seed treatment was established, to explain DON contamination of silage maize. Based on these findings, we suggest a European-wide survey on silage maize.

Understanding antibody aggregation is of great significance for the pharmaceutical industry. We studied the aggregation of five different therapeutic monoclonal antibodies (mAbs) with size-exclusion chromatography-high-performance liquid chromatography (SEC-HPLC), fluorescence spectroscopy, electron microscopy, and light scattering methods at various temperatures with the aim of gaining insight into the aggregation process and developing models of it. In particular, we find that the kinetics can be described by a second-order model and are non-Arrhenius. Thus, we develop a non-Arrhenius model to connect accelerated aggregation experiments at high temperature to long-term storage experiments at low temperature. We evaluate our model by predicting mAb aggregation and comparing it with long-term behavior. Our results suggest that the number of monomers and mAb conformations within aggregates vary with the size and age of the aggregates, and that only certain sizes of aggregates are populated in the solution. We also propose a kinetic model based on conformational changes of proteins and monomer peak loss kinetics from SEC-HPLC. This model could be employed for a detail analysis of mAb aggregation kinetics.

Radiolabelled somatostatin-based antagonists show a higher uptake in tumour-bearing mouse models than agonists of similar or even distinctly higher receptor affinity. Very similar results were obtained with another family of G protein-coupled receptor ligands, the bombesin family. We describe a new conjugate, RM2, with the chelator DOTA coupled to D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH(2) via the cationic spacer 4-amino-1-carboxymethyl-piperidine for labelling with radiometals such as (111)In and (68)Ga.RM2 was synthesized on a solid support and evaluated in vitro in PC-3 cells. IC(50) and K(d) values were determined. The antagonist potency was evaluated by immunofluorescence-based internalization and Ca(2+) mobilization assays. Biodistribution studies were performed in PC-3 and LNCaP tumour-bearing mice with (111)In-RM2 and (68)Ga-RM2, respectively. PET/CT studies were performed on PC-3 and LNCaP tumour-bearing nude mice with (68)Ga-RM2.RM2 and (111)In-RM2 are high-affinity and selective ligands for the GRP receptor (7.7 ± 3.3 nmol/l for RM2; 9.3 ± 3.3 nmol/l for (nat)In-RM2). The potent antagonistic properties were confirmed by an immunofluorescence-based internalization and Ca(2+) mobilization assays. (68)Ga- and (111)In-RM2 showed high and specific uptake in both the tumour and the pancreas. Uptake in the tumour remained high (15.2 ± 4.8%IA/g at 1 h; 11.7 ± 2.4%IA/g at 4 h), whereas a relatively fast washout from the pancreas and the other abdominal organs was observed. Uptake in the pancreas decreased rapidly from 22.6 ± 4.7%IA/g at 1 h to 1.5 ± 0.5%IA/g at 4 h.RM2 was shown to be a potent GRPr antagonist. Pharmacokinetics and imaging studies indicate that (111)In-RM2 and (68)Ga-RM2 are ideal candidates for clinical SPECT and PET studies.

Caustic regeneration procedures are often used in chromatographic purification processes of peptides and proteins to remove irreversibly bound impurities from the stationary phase. Silica-based materials are the most commonly used materials in reversed phase chromatography of peptides. Their limited chemical stability at high pH can be, however, problematic when high pH column regeneration (i.e. cleaning in place) is required. The effect of cleaning in place on the surface chemistry of the stationary phase has been investigated using the Tanaka test. It has been shown that the high pH treatment does not significantly affect the hydrophobicity of the material, but it strongly increases its silanol activity. A representative peptide purification process has been used to investigate the impact of cleaning in place on the separation performance. It has been shown that the caustic regeneration increases the peptide retention at high pH (pH 6.5), due to the interactions between the peptide and the negatively charged silanol groups. These unwanted interactions reduce the separation performances by decreasing the selectivity between the late eluting impurities and the main peptide. However, it has been shown that the effect of the silanol groups on the peptide adsorption and on the separation performance can be minimized by carrying out the purification process at low pH (pH approximately 2). In this case, the silanol groups are protonated and their electrostatic interactions with the positively charged analyte (i.e. peptides) are suppressed. In these conditions, the peptide adsorption and the impurity selectivity is not changing upon high pH column regeneration and the separation performance is not affected.

The performance of functionalized materials, such as cation exchange resins, is dependent not only on the ligand type and ligand density, but also on the pore accessibility of the target molecule. In the case of large molecules such as antibodies this latter parameter becomes crucial, because the size of such molecules falls somewhere inside the pore size distribution of the resin. The influence of the ligand density and accessibility on the overall performance of the material is explored systematically. Five different materials, having the same chemistry as the strong cation exchange resin Fractogel EMD SO(3)(-) (M) , have been analyzed. These materials only differ in the ligand density. It is shown that the ligand density directly influences the porosity of the materials as well as the pore diffusivity and the dynamic binding capacity. For a given purification problem an optimal ligand density can be found. Based on the above results a new material is proposed, showing superior properties in terms of dynamic binding capacity. This is achieved by an optimization of the ligand density and by a decrease of the particle size of the stationary phase. The material properties are modeled with a general rate model. Further simulations were conducted to evaluate the performance of the new material in comparison with a conventional resin.

Density functional theory has been used to study the electronic structure of [M(tp)] and [M(tpm)](+) conformers (M = Cu, Ag; tp = tris(pyrazol-1-yl)borate anion, tpm = tris(pyrazol-1-yl) methane) and the energetics of their interconversions. Results for the free tp ligand are similar to those of tpm [M. Casarin, D. Forrer, F. Garau, L. Pandolfo, C. Pettinari, A. Vittadini, J. Phys. Chem. A 112 (2008) 6723], indicating an intrinsic instability of the tripodal conformation (kappa(3)-like). This points out that, though frequently observed, the kappa(3)-coordinative mode is unlikely to be directly achieved through the interaction of M(I) with the kappa(3)-like tp/tpm conformer. Analogously to the [M(tpm)](+) molecular ions, the energy barrier for the kappa(2)-[M(tp)] -> kappa(3)-[M(tp)] conversion is computed to be negligible. Though kappa(n)-[M(tp)] and kappa(n)-[M(tpm)](+) (n = 1, 2, 3) have similar metal-ligand covalent interactions, the negative charge associated to the tp ligand makes the M-tp bonding stronger.