Corrigendum: Short-lived positron emitters in beam-on PET imaging during proton therapy (2015 Phys. Med. Biol. 60 8923)

Because of strong indications of multiple counting by the multi-channel scaler (MCS) during most of the experiments described in Dendooven et al (2015 Phys. Med. Biol. 60 8923–47), the production of short-lived positron emitters in the stopping of 55 MeV protons in water, carbon, phosphorus and calcium was remeasured. The new results are reported here. With proper single counting of the MCS, the new production rates are 1.1 to 2.9 times smaller than reported in Dendooven et al (2015 Phys. Med. Biol. 60 8923–47). The omission of the conversion from MCS time bin to time unit in the previous data analysis was corrected, leading to an increase of the production rate by a factor of 2.5 or 10 for some nuclides. The most copiously produced short-lived nuclides and their production rates relative to the relevant long-lived nuclides are: 12N (T 1/2  =  11 ms) on carbon (5.3% of 11C), 29P (T 1/2  =  4.1 s) on phosphorus (23% of 30P) and 38mK (T 1/2  =  0.92 s) on calcium (173% of 38gK). The number of decays integrated from the start of an irradiation as a function of time during the irradiation of PMMA and 4 tissue materials has been determined. For (carbon-rich) adipose tissue, 12N dominates up to 70 s. On bone tissue, 38mK dominates the beam-on PET counts from 0.2–0.7 s until about 80–110 s. Considering nuclides created on phosphorus and calcium, the short-lived ones provide 8 times more decays than the long-lived ones during a 70 s irradiation. Bone tissue will thus be much better visible in beam-on PET compared to PET imaging after an irradiation. From the estimated number of 12N PET counts, we conclude that, for any tissue, except carbon-poor ones, 12N PET imaging potentially provides equal quality proton range information as prompt gamma imaging with an optimized knife-edge slit camera

Biobased Furanics:Kinetic Studies on the Acid Catalyzed Decomposition of 2-Hydroxyacetyl Furan in Water Using Bronsted Acid Catalysts

Biobased furanics like 5-hydroxymethylfurfural (5-1-IMF) are interesting platform chemicals for the synthesis of biofuel additives and polymer precursors. 5-HMF is typically prepared from C6 ketoses like fructose, psicose, sorbose and tagatose. A known byproduct is 2-hydroxyacetylfuran (2-HAF), particularly when using sorbose and psicose as the reactants. We here report an experimental and kinetic modeling study on the rate of decomposition of 2-HAF in a typical reaction medium for 5-HMF synthesis (water, Bronsted acid), with the incentive to gain insights in the stability of 2-HAF. A total of 12 experiments were performed (batch setup) in water with sulfuric acid as the catalyst (100-170 degrees C, C-H2SO4 ranging between 0.033 and 1.37 M and an initial 2-HAF concentration between 0.04 and 0.26 M). Analysis of the reaction mixtures showed a multitude of products, of which levulinic acid (LA) and formic acid (FA) were the most prominent (Y-max,Y-FA = 24 mol %, Y-max,Y-LA = 10 mol %) when using HCI. In contrast, both LA and FA were formed in minor amounts when using H2SO4 as the catalyst. The decomposition reaction of 2-HAF using sulfuric acid was successfully modeled (R-2 = 0.9957) using a first-order approach in 2-1-IAF and acid. The activation energy was found to be 98.7 ( 2.2) kJ mol(-1)

Field testing and exploitation of genetically modified cassava with low-amylose or amylose-free starch in Indonesia

The development and testing in the field of genetically modified -so called- orphan crops like cassava in tropical countries is still in its infancy, despite the fact that cassava is not only used for food and feed but is also an important industrial crop. As traditional breeding of cassava is difficult (allodiploid, vegetatively propagated, outbreeding species) it is an ideal crop for improvement through genetic modification. We here report on the results of production and field testing of genetically modified low-amylose transformants of commercial cassava variety Adira4 in Indonesia. Twenty four transformants were produced and selected in the Netherlands based on phenotypic and molecular analyses. Nodal cuttings of these plants were sent to Indonesia where they were grown under biosafety conditions. After two screenhouse tests 15 transformants remained for a field trial. The tuberous root yield of 10 transformants was not significantly different from the control. Starch from transformants in which amylose was very low or absent showed all physical and rheological properties as expected from amylose-free cassava starch. The improved functionality of the starch was shown for an adipate acetate starch which was made into a tomato sauce. This is the first account of a field trial with transgenic cassava which shows that by using genetic modification it is possible to obtain low-amylose cassava plants with commercial potential with good root yield and starch quality

Lipoxygenases and Poly(ADP-Ribose) Polymerase in Amyloid Beta Cytotoxicity

The 12/15-lipoxygenase(s) (LOX), poly(ADP-ribose) polymerase (PARP-1) activity and mitochondrial apoptosis inducing factor (AIF) protein in the amyloid β (Aβ) toxicity were investigated in PC12 cells that express either wild-type (APPwt) or double Swedish mutation (APPsw) forms of human Aβ precursor protein. Different levels of Aβ secretion and free radicals formation characterize these cells. The results demonstrated a relationship between the Aβ levels and LOX protein expression and activity. High Aβ concentration in APPsw cells correlated with a significant increase in free radicals and LOX activation, which leads to translocation of p65/NF-κB into the nucleus. An increase in AIF expression in mitochondria was observed concurrently with inhibition of PARP-1 activity in the nuclear fraction of APPsw cells. We suggested that AIF accumulation in mitochondria may be involved in adaptive/protective processes. However, inhibition of PARP-1 may be responsible for the disturbances in transcription and DNA repair as well as the degeneration of APP cells. Under conditions of increased nitrosative stress, evoked by the nitric oxide donor, sodium nitroprusside (SNP, 0.5 mM), 70–80% of all cells types died after 24 h, significantly more in APPsw cells. There was no further significant change in mitochondrial AIF level and PARP-1 activity compared to corresponding non-treated cells. Only one exception was observed in PC12 control, where SNP significantly inhibits PARP-1 activity. Moreover, SNP significantly activated gene expression for 12/15-LOX in all types of investigated cells. Inhibitors of all LOX isoforms and specific inhibitor of 12-LOX enhanced the survival of cells that were subjected to SNP. We conclude that the LOX pathways may play a role in Aβ toxicity and in nitrosative-stress-induced cell death and that inhibition of these pathways offers novel protective strategies

Improvement of infrared single-photon detectors absorptance by integrated plasmonic structures

Plasmonic structures open novel avenues in photodetector development. Optimized illumination configurations are reported to improve p-polarized light absorptance in superconducting-nanowire single-photon detectors (SNSPDs) comprising short- and long-periodic niobium-nitride (NbN) stripe-patterns. In OC-SNSPDs consisting of ~quarter-wavelength dielectric layer closed by a gold reflector the highest absorptance is attainable at perpendicular incidence onto NbN patterns in P-orientation due to E-field concentration at the bottom of nano-cavities. In NCAI-SNSPDs integrated with nano-cavity-arrays consisting of vertical and horizontal gold segments off-axis illumination in S-orientation results in polar-angle-independent perfect absorptance via collective resonances in short-periodic design, while in long-periodic NCAI-SNSPDs grating-coupled surface waves promote EM-field transportation to the NbN stripes and result in local absorptance maxima. In NCDAI-SNSPDs integrated with nano-cavity-deflector-array consisting of longer vertical gold segments large absorptance maxima appear in 3p-periodic designs due to E-field enhancement via grating-coupled surface waves synchronized with the NbN stripes in S-orientation, which enable to compensate fill-factor-related retrogression.United States. Dept. of Energy (Frontier Research Centers

Expression of circ_Satb1 is decreased in mesial temporal lobe epilepsy and regulates dendritic spine morphology

Mesial temporal lobe epilepsy (mTLE) is a chronic disease characterized by recurrent seizures that originate in the temporal lobes of the brain. Anti-epileptic drugs (AEDs) are the standard treatment for managing seizures in mTLE patients, but are frequently ineffective. Resective surgery is an option for some patients, but does not guarantee a postoperative seizure-free period. Therefore, further insight is needed into the pathogenesis of mTLE to enable the design of new therapeutic strategies. Circular RNAs (circRNAs) have been identified as important regulators of neuronal function and have been implicated in epilepsy. However, the mechanisms through which circRNAs contribute to epileptogenesis remain unknown. Here, we determine the circRNA transcriptome of the hippocampus and cortex of mTLE patients by using RNA-seq. We report 333 differentially expressed (DE) circRNAs between healthy individuals and mTLE patients, of which 23 circRNAs displayed significant adjusted p-values following multiple testing correction. Interestingly, hippocampal expression of circ_Satb1, a circRNA derived from special AT-rich sequence binding protein 1 (SATB1), is decreased in both mTLE patients and in experimental epilepsy. Our work shows that circ_Satb1 displays dynamic patterns of neuronal expression in vitro and in vivo. Further, circ_Satb1-specific knockdown using CRISPR/CasRx approaches in hippocampal cultures leads to defects in dendritic spine morphology, a cellular hallmark of mTLE. Overall, our results identify a novel epilepsy-associated circRNA with disease-specific expression and previously unidentified cellular effects that are relevant for epileptogenesis

Potential biological role of poly (ADP-ribose) polymerase (PARP) in male gametes

Maintaining the integrity of sperm DNA is vital to reproduction and male fertility. Sperm contain a number of molecules and pathways for the repair of base excision, base mismatches and DNA strand breaks. The presence of Poly (ADP-ribose) polymerase (PARP), a DNA repair enzyme, and its homologues has recently been shown in male germ cells, specifically during stage VII of spermatogenesis. High PARP expression has been reported in mature spermatozoa and in proven fertile men. Whenever there are strand breaks in sperm DNA due to oxidative stress, chromatin remodeling or cell death, PARP is activated. However, the cleavage of PARP by caspase-3 inactivates it and inhibits PARP's DNA-repairing abilities. Therefore, cleaved PARP (cPARP) may be considered a marker of apoptosis. The presence of higher levels of cPARP in sperm of infertile men adds a new proof for the correlation between apoptosis and male infertility. This review describes the possible biological significance of PARP in mammalian cells with the focus on male reproduction. The review elaborates on the role played by PARP during spermatogenesis, sperm maturation in ejaculated spermatozoa and the potential role of PARP as new marker of sperm damage. PARP could provide new strategies to preserve fertility in cancer patients subjected to genotoxic stresses and may be a key to better male reproductive health

PARP-1 and YY1 Are Important Novel Regulators of CXCL12 Gene Transcription in Rat Pancreatic Beta Cells

Despite significant progress, the molecular mechanisms responsible for pancreatic beta cell depletion and development of diabetes remain poorly defined. At present, there is no preventive measure against diabetes. The positive impact of CXCL12 expression on the pancreatic beta cell prosurvival phenotype initiated this study. Our aim was to provide novel insight into the regulation of rat CXCL12 gene (Cxcl12) transcription. The roles of poly(ADP-ribose) polymerase-1 (PARP-1) and transcription factor Yin Yang 1 (YY1) in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation. The regulatory activities of PARP-1 and YY1 were assessed in transfection experiments using a reporter vector with a Cxcl12 promoter sequence driving luciferase gene expression. Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription. Streptozotocin (STZ)-induced general toxicity in pancreatic beta cells was followed by changes in Cxcl12 promoter regulation. PARP-1 binding to the Cxcl12 promoter during basal and in STZ-compromised conditions led us to conclude that PARP-1 regulates constitutive Cxcl12 expression. During the early stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter while PARP-1 displayed strong binding. These interactions were accompanied by Cxcl12 downregulation. In the later stages of oxidative stress and intensive pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12 promoter in contrast to PARP-1. These interactions resulted in higher Cxcl12 expression. The observed ability of PARP-1 to downregulate, and of YY1 to upregulate Cxcl12 promoter activity anticipates corresponding effects in the natural context where the functional interplay of these proteins could finely balance Cxcl12 transcription

Once the shovel hits the ground : Evaluating the management of complex implementation processes of public-private partnership infrastructure projects with qualitative comparative analysis

Much attention is being paid to the planning of public-private partnership (PPP) infrastructure projects. The subsequent implementation phase – when the contract has been signed and the project ‘starts rolling’ – has received less attention. However, sound agreements and good intentions in project planning can easily fail in project implementation. Implementing PPP infrastructure projects is complex, but what does this complexity entail? How are projects managed, and how do public and private partners cooperate in implementation? What are effective management strategies to achieve satisfactory outcomes? This is the fi rst set of questions addressed in this thesis. Importantly, the complexity of PPP infrastructure development imposes requirements on the evaluation methods that can be applied for studying these questions. Evaluation methods that ignore complexity do not create a realistic understanding of PPP implementation processes, with the consequence that evaluations tell us little about what works and what does not, in which contexts, and why. This hampers learning from evaluations. What are the requirements for a complexity-informed evaluation method? And how does qualitative comparative analysis (QCA) meet these requirements? This is the second set of questions addressed in this thesis