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Understanding animal emotions is an important scientific and ethical question but assessing emotional valence is still considered challenging. As the observation of lateralization (hemispheric asymmetries in structure and/or function) can provide insight into the underlying processes of the cognitive, physiological and behavioural components of emotions, it is a promising approach for studying them. The emotional valence hypothesis states that positive emotions are mostly processed by the left hemisphere, while negative emotions are mostly processed by the right hemisphere. Support for this hypothesis is still not conclusive; therefore, our study tested it in the context of visual laterality for viewing positive or negative emotionally conditioned stimuli. Ninety male piglets were either positively (food-reward) or negatively (mild punishment) conditioned to an object. Afterwards, the object was presented without the reinforcer under three different treatments: patch on the left or right eye (reducing input to the contralateral hemisphere) or patch between the eyes (the control). Monocular viewing had no clear effects on the negatively conditioned subjects. In contrast, in the positively conditioned group, covering the right eye caused a longer interruption of vocalization, a longer latency to touch the object, a shorter duration of exploring the arena and an increased vagal activity compared to the control. This suggests that reduced processing in the left hemisphere leads to heightened attention that is accompanied by a general orienting response, possibly resulting from a reduced positive appraisal. These findings therefore partially support the emotional valence hypothesis and suggest an important role of the left hemisphere in the quick recognition of a positive stimulus. This study demonstrated that investigating the lateralized processing of emotions can provide insight into the mechanisms of positive appraisal in animals.

Designing supervisory controllers for high-tech systems is a laborious and error-prone process. Model-driven software engineering methods can help in increasing the quality and productivity by automation of various steps in the design process. Supervisory control synthesis (SCS) is such a method. SCS is a formal method that can be used to synthesize a supervisor for a system from the uncontrolled plant model and the requirements model. Subsequently, this supervisor can be used to generate controller code. While SCS is an active research topic, reports on industrial applications are rare. One of the main reasons for this is that until recently synthesis techniques were unable to scale to industrial-size problems. Due to advances in computation power, memory availability, and synthesis algorithms, synthesis techniques have matured to a point where they are capable of being applied to industrial-size problems. This paper presents a method for modeling, synthesis, validation, code generation, and implementation of fault-tolerant supervisory controllers. To illustrate this method, a case is described where a supervisory controller for a movable bridge has been synthesized, validated, implemented, and tested. With this case study, it is shown that synthesis techniques have reached a critical point where they are powerful enough to be applied in practice.

Item does not contain fulltext Autosomal dominant polycystic kidney disease (ADPKD) patients can suffer from chronic pain that can be refractory to conventional treatment, resulting in a wish for nephrectomy. This study aimed to evaluate the effect of a multidisciplinary treatment protocol with sequential nerve blocks on pain relief in ADPKD patients with refractory chronic pain. As a first step a diagnostic, temporary celiac plexus block with local anesthetics was performed. If substantial pain relief was obtained, the assumption was that pain was relayed via the celiac plexus and major splanchnic nerves. When pain recurred, patients were then scheduled for a major splanchnic nerve block with radiofrequency ablation. In cases with no pain relief, it was assumed that pain was relayed via the aortico-renal plexus, and catheter-based renal denervation was performed. Sixty patients were referred, of which 44 were eligible. In 36 patients the diagnostic celiac plexus block resulted in substantial pain relief with a change in the median visual analogue scale (VAS) score pre-post intervention of 50/100. Of these patients, 23 received a major splanchnic nerve block because pain recurred, with a change in median VAS pre-post block of 53/100. In 8 patients without pain relief after the diagnostic block, renal denervation was performed in 5, with a borderline significant change in the median VAS pre-post intervention of 20/100. After a median follow-up of 12 months, 81.8% of the patients experienced a sustained improvement in pain intensity, indicating that our treatment protocol is effective in obtaining pain relief in ADPKD patients with refractory chronic pain.

The growing recognition of animals as individuals has broader implications for farm animal welfare research. Even under highly standardized on-farm conditions, farm animals show heterogeneous but individually consistent behavioural patterns towards various stimuli, based on how they appraise these stimuli. As a result, animal welfare is likely to be highly individual as well, and studying the proximate mechanisms underlying distinct individual behaviour patterns and appraisal will improve animal welfare research. We propose to extend the framework of affective styles to bridge the gap between existing research fields on animal personality and affective states. Affective styles refer to consistent individual differences in emotional reactivity and regulation and can be predicted by baseline cerebral lateralization. Likewise, animals with consistent left or right motor biases—a proxy measure of individual patterns in cerebral lateralization—have been shown to differ in their personality, emotional reactivity, motivational tendencies or coping styles. In this paper, we present the current knowledge of the links between laterality and stable individual traits in behaviour and affect in light of hypotheses on emotional lateralization. Within our suggested framework, we make recommendations on how to investigate affective styles in non-human animals and give practical examples. This approach has the potential to promote a science of affective styles in nonhuman animals and significantly advance research on animal welfare.

The number of elderly patients with renal cell carcinoma is rising. Elderly patients differ from their younger counterparts in, among others, higher incidence of comorbidity and reduced organ function. Age influences outcome of surgery, and therefore has to be taken into account in elderly patients eligible for cytoreductive nephrectomy. Over the last decade several novel effective drugs have become available for the metastatic setting targeting angiogenesis and mammalian target of rapamycin. Immune checkpoint blockade with a programmed death 1 antibody has recently been shown to increase survival and further studies with immune checkpoint inhibitors are ongoing. In this review we summarize the available data on efficacy and toxicity of existing and emerging therapies for metastatic renal cell carcinoma in the elderly. Where possible, we provide evidence-based recommendations for treatment choices in elderly. (C) 2016 The Authors. Published by Elsevier Ltd.

This study aimed to determine the effects of weaning age and postweaning feeding programme on pig performance and health. In experiment 1, 96 same gender pairs of pigs weaned at 3, 4 and 5 weeks of age were used in a 3 (weaning age)×4 (dietary programme) factorial design experiment. Pigs received different amounts of a phase 1 diet (16.2 MJ/kg digestible energy (DE) and 16.2 g/kg lysine) and phase 2 diet (15.3 MJ/kg DE and 15.0 g/kg lysine): (A) very low (VL, 1 kg phase 1 and 3 kg phase 2 diet per pig); (B) low (L, 2 kg phase 1 and 6 kg phase 2 diet per pig); (C) medium (M, 3 kg phase 1 and 9 kg phase 2 diet per pig) or (D) high (H, 4 kg phase 1 and 12 kg phase 2 diet per pig), followed by a cereal based phase 3 diet (15.0 MJ/kg DE and 13.8 g/kg lysine) to 10 weeks of age. In experiment 2, faecal samples from 60 pigs weaned at 3, 4 and 5 weeks of age were collected at 10 days postweaning and analysed for Escherichia coli and lactic acid bacteria counts. In experiment 1, there were no interaction effects of age×dietary programme on growth performance. Dietary programme did not affect growth performance from weaning to 10 weeks of age. From weaning to 10 weeks of age, increasing weaning age increased average daily gain (ADG; 363, 402, and 476 g for 3, 4 and 5 weeks respectively; s.e. 17.6; P 0.05) on pig weight at 10 weeks of age. In experiment 2, 3 week weaned pigs had higher faecal counts of E. coli (P 0.01) than 5 week weaned pigs at 10 days postweaning. In conclusion, feeding higher amounts of phases 1 and 2 diets did not affect performance at any of the weaning ages tested. Increasing weaning age increased growth performance between weaning and 10 weeks of age, but had no effect on the resulting body weight. Pigs weaned at 3 weeks of age had increased counts of selected faecal bacteria compared to those weaned later.

The study and protection of animal welfare are based on the assumption that animals are sentient beings, capable of experiencing emotions. Still, our understanding of animal emotions is limited. In this review we focus on the potential of cerebral-lateralization research to provide new insights into animal emotional processing. Thereby, our aims were, first, to find a universal lateralization pattern in emotional processing across vertebrates and, second, to discuss how knowledge of emotional-lateralization patterns can be used in science and practice to contribute to improve farm-animal welfare. A literature review suggests evidence of lateralized functioning during emotional contexts across the vertebrate classes, from early vertebrates such as fish and amphibians to non-human primates. With the possible exception of fish, all vertebrate classes seem to show a similar lateralization pattern for emotional processing, with a right-hemisphere dominance for processing rather negatively connotated emotions, such as fear and aggression, and a left-hemisphere dominance for processing positively connotated emotions, such as those elicited by a food reward. Thus, both hemispheres are involved in emotional processing and hemispheric dominance may be used as an indicator of emotional valence (negative-positive). Although only a few domestic animal species (e.g. chicken, sheep, dog and horse) have been extensively studied with regard to emotional lateralization, evidence gathered so far suggests that the right-hemisphere dominance for fear and aggression and left-hemisphere dominance in responses to food rewards also applies to these species. Such patterns could be exploited in animal welfare studies to gain insight into how an animal experiences a potentially emotional situation and to improve farm-animal management. Further research should focus on rarely-studied species and on rarely-studied emotional contexts, such as sex and positive social situations, to improve our understanding of animal emotional lateralization.

Background Both disrupted-in-schizophrenia 1 ( DISC1 ) and dysbindin have been identified as schizophrenia candidate genes in independent genetic linkage studies. The proteins have been assigned distinct subcellular locations and functions. We investigated whether both proteins converge into a common pathway specific for schizophrenia or mental diseases. Methods DISC1 and dysbindin were expressed as recombinant proteins with or without a fluorescent protein-tag in human or mouse neuroblastoma cells and as recombinant proteins in E. coli . Postmortem brains of patients with mental diseases from the Stanley Research Medical Institute's Consortium Collection were used to demonstrate molecular interactions in biochemically purified protein fractions. Results First, upon overexpression in neuroblastoma cells, DISC1 formed aggresomes that recruited homologous soluble C-terminal DISC1 fragment or heterologous dysbindin. Domains involved in binding could be mapped to DISC1 (316-597) and dysbindin (82-173), indicating a specific interaction. In addition, recruitment was demonstrated when externally added, purified DISC1 aggresomes penetrated recipient cells after coincubation. Second, a direct interaction between soluble DISC1 protein and dysbindin was demonstrated in a cell free system using E. coli -expressed proteins. Third, co-aggregation of DISC1 and dysbindin was demonstrated in postmortem brains for a subgroup of cases with chronic mental disease but not healthy control subjects. Conclusions A direct interaction of soluble and insoluble DISC1 protein with dysbindin protein demonstrates convergence of so far considered independent mental disease genes by direct molecular interaction. Our findings highlight protein aggregation and recruitment as a biological mechanism in mental disease.

In this article we give a systematic review of the nature and design of earlier research into the impact of instructional development in higher education. Studies are clustered on the basis of the level of outcome that was measured, meaning that another synthesis technique is used than in prior reviews related to the same topic. In addition, we address some questions related to the differential impact of initiatives with varied duration, format, or target group, because these questions were left unanswered in earlier reviews. The results of our review provide a guide to improve studies of instructional development in order to get more insight into the real impact at different levels (teachers’ learning, teachers’ behavior, the institution, and the students). Some evidence is found of the influence of the duration and nature of instructional development on its impact.

"In this study we investigate how outcome valence affects the importance of self-interest and fairness in ultimatum bargaining. In three experiments we systematically study the effect of outcome valence on fairness accessibility, norms, and behavior. Results on all three aspects show strong evidence for the hypothesis that fairness becomes more important and self-interest becomes less important in negative valence bargaining. Fairness accessibility was higher when bargaining involved negative payoffs than when it involved positive payoffs (Experiment 1), the fairness norm was stronger in negatively versus positively valenced bargaining when an identical unequal offer benefiting the allocators was evaluated (Experiment 2), and allocators allocated more to recipients in negative valence bargaining than in positive valence bargaining (Experiment 3). We relate our findings to insights derived from the do-no-harm principle." [author's abstract]

Hydroprocessing as a catalytic refinery process is over 70 years old. Currently strong economic, environmental and social drivers are pushing the oil industry to produce more and higher quality fuels. Hydroprocessing is the turnkey technology of choice for refineries to meet these commercial demands and, consequently, catalyst vendors are being asked to design and develop more active and more selective catalysts. As a result, continuous innovation has been taking place and tremendous progress has been made in understanding the preparation and activity responses of these catalysts. Today, the refinery industry asks for “tailored, fit for purpose” hydroprocessing catalysts to meet their commercial goals. To meet such goals requires a deeper understanding of the complexities associated with commercial catalysts. This is a clear challenge for both academia and industry to gain the required knowledge to design and develop new and improved catalysts.

Raman microspectroscopy was used to study the preparation of industrial MoS2/Al2O3 extrudates. Using this technique, the influence of the impregnation solution composition on the nature and macrodistribution of Mo complexes inside these catalyst bodies was evaluated during their preparation process (impregnation, drying, and calcination). It was found that poor dispersion of the MoOx phase in the calcined samples can be brought about by the formation of bulk (NH4)3[Al(OH)6Mo6O18] during impregnation or redistribution of Mo complexes during drying. The formation of crystalline MoO3 and Al2(MoO4)3 in the oxidic precursors leads to a poorly dispersed MoS2 phase in the final catalyst and significantly lower hydrodesulfurization activity. The spatially resolved information that can be obtained, and its inherent sensitivity for the detection of crystalline phases make Raman microspectroscopy a powerful characterization technique for studying the preparation of industrial supported metal oxide catalysts.

The chicken anemia virus-derived protein Apoptin induces apoptosis specifically in human tumor and transformed cells and not in normal, untransformed cells. The cell killing activity correlates with a predominantly nuclear localization of Apoptin in tumor cells, whereas in normal cells, it is detected mainly in cytoplasmic structures. To explore the role of nuclear localization for Apoptin-induced cell death in tumor cells, we employed a mutagenesis strategy. First, we demonstrated that the C terminus of Apoptin contains a bipartite-type nuclear localization signal. Strikingly, further investigation showed that Apoptin contains two different domains that induce apoptosis independently, and for both domains, we found a strong correlation between localization and killing activity. Using inhibitors, we ruled out the involvement of de novo gene transcription and translation and further showed that Apoptin itself does not have any significant transcriptional repression activity, suggesting that Apoptin exerts its effects in the nucleus by some other method. To determine whether nuclear localization is sufficient to enable Apoptin to kill normal, untransformed cells, we expressed full-length Apoptin fused to a heterologous nuclear localization signal in these cells. However, despite its nuclear localization, no apoptosis was induced, which suggests that nuclear localization per se is not sufficient for Apoptin to become active. These studies increase our understanding of the molecular pathway of Apoptin and may also shed light on the mechanism of cellular transformation.

The influence of the Si/Al ratio of the support of (Co)Mo/saponite catalysts on the performance in the hydrodesulfurisation of thiophene and hydrocracking of n-decane has been studied. The initial thiophene HDS activity of the sulfided Co catalysts increased with increasing support acidity, while with the CoMo catalysts the opposite effect was observed. The large drop in activity at lower Si/Al ratios is ascribed to the occurrence of two separate cobalt and molybdenum sulfide phases instead of the “Co‐Mo‐S” phase. In the hydrocracking of n-decane both the Co and the CoMo catalysts displayed an almost linear relationship between the first-order rate constant and the number of Bronsted acid sites. As with zeolite catalysts the Si/Al ratio was also found to affect the product selectivity. At low Si/Al ratios the relative amount of secondary cracking products increased due to a changing balance between the number of cracking and hydrogenation sites. Remarkably, it was found that in the presence of H2S between 423 and 573 K the n-decane conversion passes through a maximum. The observed relation between this “low-temperature” activity and the number of Bronsted acid sites seem to indicate the involvement of both H2S and the acid sites on the support. c ∞ 1999 Academic Press

Background: The treatment landscape of metastatic castration resistant prostate cancer (mCRPC) has changed with the introduction of abiraterone acetate (AA), enzalutamide (EN) and radium-223 (Ra-223). Little is known about the cost-effectiveness of these novel agents. This study investigates the cost-effectiveness of Ra-223 in the Netherlands. First, the costeffectiveness of Ra-223 will be evaluated against best supportive care (BSoC) in the mCRPC population. Second, the cost-effectiveness of Ra-223 in the post-chemo setting will be evaluated against the active comparators AA and EN. Material and Methods: A Markov model with five health states is used to describe disease progression and evaluate the cost-effectiveness. The health states are: progression-free survival (PFS) without a symptomatic skeletal event (SSE), progressed disease without SSE, PFS after experiencing a SSE, progressed disease after experiencing a SSE, and death. Disease progression is measured by alkaline phosphatase (comparator=BSoC) or prostate specific antigen. Efficacy, safety and quality adjusted life year (QALY) data were extracted from Phase III RCT's. Efficacy and safety of Ra-223 versus AA and EN was obtained by indirect treatment comparisons. The model has been validated by specialists treating mCRPC. Analyses were performed from a societal perspective, including costs outside the health care budget. Results: Compared to BSoC, Ra-223 has higher quality adjusted survival (0.29 QALYs) and lifetime costs (€22.485) in mCRPC patients, resulting in an incremental cost-effectiveness ratio of €78.642 per QALY. This is below the proposed Dutch threshold of €80.000. Probabilistic sensitivity analyses reveal a 33% chance for Ra-223 to be cost-effective compared to BSoC at this threshold. Cost-effectiveness of Ra-223 in the postchemo setting compared to active comparators is as follows. While quality adjusted survival of Ra-223 is similar to AA, Ra-223 has lower lifetime costs (€5.905), which are mainly driven by lower drug and SSE treatment costs. Probabilistic sensitivity analyses show a 78% chance for Ra-223 to be cost-effective compared to AA at a threshold of €80.000. Compared to EN, Ra-223 has a slightly lower QALY gain (-0.06) and lower lifetime costs (-€7.255), resulting in only a 19% chance of EN to be cost-effective compared to Ra-223 at a €80.000 threshold. Conclusions: Our model suggests that Ra-223 may be cost-effective compared to BSoC and AA in the Netherlands, with Ra-223 even dominating AA (evaluated in post-chemo patients only). Although EN may lead to slightly more health in post-chemo patients, this health gain is accompanied by extra costs resulting in EN not being considered costeffective compared to Ra-223 according to the Dutch threshold. Ra-223's cost-effectiveness compared to AA and EN should be interpreted with caution due to indirect treatment comparisons.

This work demonstrates that non-physiological electron transfer (ET) can occur in solution between wild type D. vulgaris flavodoxin (Fld) and horse heart cytochrome c (cyt-c), D. vulgaris cytochrome c553 (cyt-c553) and the haem domain of B. megaterium cytochrome P450 (cyt-P450 BMP). Second order rate constants of the ET reaction between [Fld]sq/[cyt-c]ox, [Fld]sq/[cyt-c553]ox and [Fld]sq/[cyt-P450 BMP]ox, were found to be 6.16 x 10(5), 1.80 x 10(4) and in the region of 10(5) respectively. These data are interpreted in terms of complementarity between the surfaces of the two proteins, their surface and redox potentials. Analysis of the ET results obtained from the separate wild type proteins supported the rational design approach in the creation of Fld-based chimeras. The preliminary design of the chimeras reported here is a 3D prototype for an artificial flavo-cytochrome obtained by covalent linkage of a Fld module to cyt-c553 via a disulphide bond. Theoretical ET rates calculated on the modelled flavo-cytochrome are encouraging the construction of these chimeric systems at DNA level. This work is now underway. The relevance of this molecular lego approach is to be seen in the long term goal of producing engineered multi-domain systems to be applied in the field of biosensors and bioelectronics to fulfil specific requirements. Novel catalytic devices can be obtained by using natural redox proteins in different combinations: this process mimics the natural evolution of proteins such as gene shuffling and gene fusion.

Acoustophoresis has been used to investigate the interaction between suspended mineral oxides (SiO2 and Al2O3) and aqueous solutions of cobalt (II) chloride, molybdenum (III) chloride and ammonium heptamolybdate (AHM) as a function of the pH. The measured electrokinetic sonic amplitude (ESA) is directly related to the ζ-potential and gives information on the iso-electric point of the mineral oxides, that are used as supports for catalysts. The interaction between the solutes and the suspended mineral oxides is an important parameter for the preparation of supported catalysts, which can be studied perfectly by means of acoustophoresis. The specific adsorption of cobalt and molybdenum on silica and alumina has been considered.

The (dis)similarities between the Selective Catalytic Reduction (SCR) of NO and the Selective Catalytic Oxidation (SCO) of NH3 are briefly reviewed. Since the SCO reaction acts counterproductively in the SCR reaction the two processes are related. A series of V2O5, MoO3, and WO3 catalysts on various supports have been tested in the SCO reaction. It appears that an acid metal oxide in combination with an acid support gives the most active catalysts. The main byproduct is NO; minor amounts of N2O are formed. NO formation occurs in the temperature regime where the reduction of oxide lattice is faster than the recombination of two nitrogen atoms. High partial pressures of NH3 give rise to elevated selectivity to N2. This can be understood by assuming that the recombination probability of two nitrogen atoms becomes higher. A reaction mechanism, entitled the ‘internal SCR mechanism’ is proposed to explain the formation of N2O.