Spontaneous symmetry breaking and the p→0p \to 0 limit

We point out a basic ambiguity in the $p \to 0$ limit of the connected propagator in a spontaneously broken phase. This may represent an indication that the conventional singlet Higgs boson, rather than being a purely massive field, might have a gap-less branch. This would dominate the energy spectrum for ${\bf{p}} \to 0$ and give rise to a very weak, long-range force. The natural interpretation is in terms of density fluctuations of the `Higgs condensate': in the region of very long wavelengths, infinitely larger than the Fermi scale, it cannot be treated as a purely classical c-number field.Comment: 17 pages, LaTex, small changes and some comments adde

Working memory deficits in high-functioning adolescents with autism spectrum disorders: neurpsychological and neuroimaging correlates

Working memory is a temporary storage system under attentional control. It is believed to play a central role in online processing of complex cognitive information and may also play a role in social cognition and interpersonal interactions. Adolescents with a disorder on the autism spectrum display problems in precisely these domains. Social impairments, communication difficulties, and repetitive interests and activities are core domains of autism spectrum disorders (ASD), and executive function problems are often seen throughout the spectrum. As the main cognitive theories of ASD, including the theory of mind deficit hypotheses, weak central coherence account, and the executive dysfunction theory, still fail to explain the broad spectrum of symptoms, a new perspective on the etiology of ASD is needed. Deficits in working memory are central to many theories of psychopathology, and are generally linked to frontal-lobe dysfunction. This article will review neuropsychological and (functional) brain imaging studies on working memory in adolescents with ASD. Although still disputed, it is concluded that within the working memory system specific problems of spatial working memory are often seen in adolescents with ASD. These problems increase when information is more complex and greater demands on working memory are made. Neuroimaging studies indicate a more global working memory processing or connectivity deficiency, rather than a focused deficit in the prefrontal cortex. More research is needed to relate these working memory difficulties and neuroimaging results in ASD to the behavioral difficulties as seen in individuals with a disorder on the autism spectru

Encoding order and developmental dyslexia:a family of skills predicting different orthographic components

We investigated order encoding in developmental dyslexia using a task that presented nonalphanumeric visual characters either simultaneously or sequentially—to tap spatial and temporal order encoding, respectively—and asked participants to reproduce their order. Dyslexic participants performed poorly in the sequential condition, but normally in the simultaneous condition, except for positions most susceptible to interference. These results are novel in demonstrating a selective difficulty with temporal order encoding in a dyslexic group. We also tested the associations between our order reconstruction tasks and: (a) lexical learning and phonological tasks; and (b) different reading and spelling tasks. Correlations were extensive when the whole group of participants was considered together. When dyslexics and controls were considered separately, different patterns of association emerged between orthographic tasks on the one side and tasks tapping order encoding, phonological processing, and written learning on the other. These results indicate that different skills support different aspects of orthographic processing and are impaired to different degrees in individuals with dyslexia. Therefore, developmental dyslexia is not caused by a single impairment, but by a family of deficits loosely related to difficulties with order. Understanding the contribution of these different deficits will be crucial to deepen our understanding of this disorder

Direct bandgap quantum wells in hexagonal Silicon Germanium

Silicon is indisputably the most advanced material for scalable electronics, but it is a poor choice as a light source for photonic applications, due to its indirect band gap. The recently developed hexagonal Si1−xGex semiconductor features a direct bandgap at least for x &gt; 0.65, and the realization of quantum heterostructures would unlock new opportunities for advanced optoelectronic devices based on the SiGe system. Here, we demonstrate the synthesis and characterization of direct bandgap quantum wells realized in the hexagonal Si1−xGex system. Photoluminescence experiments on hex-Ge/Si0.2Ge0.8 quantum wells demonstrate quantum confinement in the hex-Ge segment with type-I band alignment, showing light emission up to room temperature. Moreover, the tuning range of the quantum well emission energy can be extended using hexagonal Si1−xGex/Si1−yGey quantum wells with additional Si in the well. These experimental findings are supported with ab initio bandstructure calculations. A direct bandgap with type-I band alignment is pivotal for the development of novel low-dimensional light emitting devices based on hexagonal Si1−xGex alloys, which have been out of reach for this material system until now.</p

A review of the dodo and its ecosystem: insights from a vertebrate concentration Lagerstätte in Mauritius

The dodo Raphus cucullatus Linnaeus, an extinct and flightless, giant pigeon endemic to Mauritius, has fascinated people since its discovery, yet has remained surprisingly poorly known. Until the mid-19th century, almost all that was known about the dodo was based on illustrations and written accounts by 17th century mariners, often of questionable accuracy. Furthermore, only a few fragmentary remains of dodos collected prior to the bird's extinction exist. Our understanding of the dodo's anatomy was substantially enhanced by the discovery in 1865 of subfossil bones in a marsh called the Mare aux Songes, situated in southeastern Mauritius. However, no contextual information was recorded during early excavation efforts, and the majority of excavated material comprised larger dodo bones, almost all of which were unassociated. Here we present a modern interdisciplinary analysis of the Mare aux Songes, a 4200-year-old multitaxic vertebrate concentration Lagerstätte. Our analysis of the deposits at this site provides the first detailed overview of the ecosystem inhabited by the dodo. The interplay of climatic and geological conditions led to the exceptional preservation of the animal and associated plant remains at the Mare aux Songes and provides a window into the past ecosystem of Mauritius. This interdisciplinary research approach provides an ecological framework for the dodo, complementing insights on its anatomy derived from the only associated dodo skeletons known, both of which were collected by Etienne Thirioux and are the primary subject of this memoir.publishedVersio

The yin-yang of drug discovery: adverse effects create an opportunity

The yin-yang of drug discovery: side effects create opportunities Psoriasis Psoriasis is a common skin disease hallmarked by well-demarcated and erythemous plaques and excessive scaling caused by the hyperproliferative state of skin cells. Treatment of the affected skin with ointments or creams is often sufficient in patients who are mildly or moderately affected. No effect without side effect When developing a new drug against the malaria parasite, we tested compounds for undesirable side effects against human cells. An unexpected activity of some of these compounds was that they appeared to be able to inhibit cell division of human skin cells, without causing cell death. We realized that this side effect can have a positive effect for psoriasis patients if we applied these substances to their affected skin. The hyperproliferative cell division of the skin can be prevented, resulting in the disappearance of the scaly plaques. This hypothesis was investigated in this project. Study design Compounds were first tested on submerged keratinocytes. Subsequently, the most active compounds were tested in a 3D reconstructed skin model. Finally, the best compound was tested in an in vivo psoriasis model. The chemical structures of the proprietary compounds used in the study cannot be disclosed. Results We have tested more than 500 compounds for their effect on proliferating skin cells. We then tested the most promising compounds in a so-called human 3D skin model. This is a reconstructed skin model that is grown in the laboratory. Finally, we tested the most active compound in a psoriasis animal model. Unfortunately, we did not see a significant positive effect of this compound on the proliferative skin. Conclusion The initial finding that our compounds have an inhibitory effect on proliferating skin cells has unfortunately not yet led to a new therapy. It may be difficult for the compound to penetrate through the skin to the dividing cells. Another explanation would be that the compounds are not active enough to show an effect in this model. In this case, chemical optimization of the compounds could be beneficial. The research described here could then be used as preliminary work to determine a so-called structure activity relationship (SAR), from which targeted optimization can take place. Abbreviations PCK: Population Control Keratinocytes This dataset contains the following files: Submerged.pdf Growth inhibiting effect of compounds on primary human keratinocytes at a concentration of 10 uM. Primary human keratinocytes were grown in triplicate in 96 well plates until they reach a confluency of 30-40%. Compounds are added at a concentration of 10 uM and after 72 hours the confluency was measured using CyQuant Direct Cell Proliferation Assay Kit. Cytotoxicity was measured using a LDH cytotoxicity assay kit. No cytotoxicity was observed. Growth effect was divided in three groups: no effect (70-100% confluency), small effect (50-70% confluency) or strong effect (30-50% confluency). Submerged_dilution_range.pdf Concentration (uM) of compounds that inhibit growth of three different primary human keratinocyte donors. Primary human keratinocytes were grown in triplicate in 96 well plates until they reach a confluency of 30-40%. Compounds are added at in a concentration range of 2-10 uM and after 72 hours the confluency was measured using CyQuant Direct Cell Proliferation Assay Kit. Cytotoxicity was measured using a LDH cytotoxicity assay kit. No cytotoxicity was observed. The concentration at which each compound inhibits cell growth for each donor was put in the table. HE_2_donors_IL4,_2_compounds_concentration_range.pdf Effect of a dilution range (30 uM – 300 nM) of two compounds (CXP18.6-017 and CXP18.6-064) on 3D reconstructed skin after stimulation with IL-4 (10 ng/ml). Constructs are stained with H/E. HE_3_donor_IL4,_12,_17_en_64_100_uM.pdf Effect of three compounds (CXP18.6-012, CXP18.6-017 and CXP18.6-064) at a concentration of 100 uM on 3D reconstructed skin after stimulation with IL-4 (10 ng/ml). Constructs are stained with H/E. Ki-67_donors_IL4,_2_compounds-concentration_range.pdf Effect of a dilution range (30 uM – 300 nM) of two compounds (CXP18.6-017 and CXP18.6-064) on 3D reconstructed skin after stimulation with IL-4 (10 ng/ml). Constructs are stained with Ki-67. Ki-67_2_donors,_2_compounds,_3_stimuli.pdf Effect of two compounds (CXP18.6-017 and CXP18.6-064) on 3D reconstructed skin after stimulation with IL-4 (20 ng/ml), IL-17/IL-22 (30/30 ng/ml) and IL-4/IL-13 (20/20 ng/ml). Constructs are stained with Ki-67. IMQ_model_with_compound.pdf Imiquimod model to test in vivo efficacy of compound CXP18.6-017 on proliferative skin. The protocol is explained in de file. Hyperproliferation of the back skin of mice was induced by Imiquimod. Treatment with CXP18.6-017 (1% in gel) was initiated two days before the Imiquimod treatment

Analysis of keratinocyte gene expression: a tale of molecules, markers, models and medicines

Contains fulltext : 11157.pdf (publisher's version ) (Open Access)Radboud Universiteit Nijmegen, 26 juni 2013Promotor : Schalkwijk, J. Co-promotor : Zeeuwen, P.L.J.M

The yin-yang of drug discovery: adverse effects create an opportunity: No effect without side effect

The yin-yang of drug discovery: side effects create opportunities Psoriasis Psoriasis is a common skin disease hallmarked by well-demarcated and erythemous plaques and excessive scaling caused by the hyperproliferative state of skin cells. Treatment of the affected skin with ointments or creams is often sufficient in patients who are mildly or moderately affected. No effect without side effect When developing a new drug against the malaria parasite, we tested compounds for undesirable side effects against human cells. An unexpected activity of some of these compounds was that they appeared to be able to inhibit cell division of human skin cells, without causing cell death. We realized that this side effect can have a positive effect for psoriasis patients if we applied these substances to their affected skin. The hyperproliferative cell division of the skin can be prevented, resulting in the disappearance of the scaly plaques. This hypothesis was investigated in this project. Study design Compounds were first tested on submerged keratinocytes. Subsequently, the most active compounds were tested in a 3D reconstructed skin model. Finally, the best compound was tested in an in vivo psoriasis model. The chemical structures of the proprietary compounds used in the study cannot be disclosed. Results We have tested more than 500 compounds for their effect on proliferating skin cells. We then tested the most promising compounds in a so-called human 3D skin model. This is a reconstructed skin model that is grown in the laboratory. Finally, we tested the most active compound in a psoriasis animal model. Unfortunately, we did not see a significant positive effect of this compound on the proliferative skin. Conclusion The initial finding that our compounds have an inhibitory effect on proliferating skin cells has unfortunately not yet led to a new therapy. It may be difficult for the compound to penetrate through the skin to the dividing cells. Another explanation would be that the compounds are not active enough to show an effect in this model. In this case, chemical optimization of the compounds could be beneficial. The research described here could then be used as preliminary work to determine a so-called structure activity relationship (SAR), from which targeted optimization can take place. Abbreviations PCK: Population Control Keratinocytes This dataset contains the following files: Submerged.pdf Growth inhibiting effect of compounds on primary human keratinocytes at a concentration of 10 uM. Primary human keratinocytes were grown in triplicate in 96 well plates until they reach a confluency of 30-40%. Compounds are added at a concentration of 10 uM and after 72 hours the confluency was measured using CyQuant Direct Cell Proliferation Assay Kit. Cytotoxicity was measured using a LDH cytotoxicity assay kit. No cytotoxicity was observed. Growth effect was divided in three groups: no effect (70-100% confluency), small effect (50-70% confluency) or strong effect (30-50% confluency). Submerged_dilution_range.pdf Concentration (uM) of compounds that inhibit growth of three different primary human keratinocyte donors. Primary human keratinocytes were grown in triplicate in 96 well plates until they reach a confluency of 30-40%. Compounds are added at in a concentration range of 2-10 uM and after 72 hours the confluency was measured using CyQuant Direct Cell Proliferation Assay Kit. Cytotoxicity was measured using a LDH cytotoxicity assay kit. No cytotoxicity was observed. The concentration at which each compound inhibits cell growth for each donor was put in the table. HE_2_donors_IL4,_2_compounds_concentration_range.pdf Effect of a dilution range (30 uM – 300 nM) of two compounds (CXP18.6-017 and CXP18.6-064) on 3D reconstructed skin after stimulation with IL-4 (10 ng/ml). Constructs are stained with H/E. HE_3_donor_IL4,_12,_17_en_64_100_uM.pdf Effect of three compounds (CXP18.6-012, CXP18.6-017 and CXP18.6-064) at a concentration of 100 uM on 3D reconstructed skin after stimulation with IL-4 (10 ng/ml). Constructs are stained with H/E. Ki-67_donors_IL4,_2_compounds-concentration_range.pdf Effect of a dilution range (30 uM – 300 nM) of two compounds (CXP18.6-017 and CXP18.6-064) on 3D reconstructed skin after stimulation with IL-4 (10 ng/ml). Constructs are stained with Ki-67. Ki-67_2_donors,_2_compounds,_3_stimuli.pdf Effect of two compounds (CXP18.6-017 and CXP18.6-064) on 3D reconstructed skin after stimulation with IL-4 (20 ng/ml), IL-17/IL-22 (30/30 ng/ml) and IL-4/IL-13 (20/20 ng/ml). Constructs are stained with Ki-67. IMQ_model_with_compound.pdf Imiquimod model to test in vivo efficacy of compound CXP18.6-017 on proliferative skin. The protocol is explained in de file. Hyperproliferation of the back skin of mice was induced by Imiquimod. Treatment with CXP18.6-017 (1% in gel) was initiated two days before the Imiquimod treatment

Chemical biology tools to study pantetheinases of the vanin family

Item does not contain fulltextVNNs (vanins) are pantetheinases that hydrolyse pantetheine to pantothenic acid and cysteamine. Studies with Vnn1-knockout mice have indicated a role of VNN-1 in inflammation and stress responses. VNN-1 is highly expressed in liver and is under transcriptional control of PPAR (peroxisome-proliferator-activated receptor)-alpha and nutritional status, suggesting a role in energy metabolism. Recently, the specific substrates and inhibitors of VNNs were obtained as tools to study VNN biology and to investigate whether VNNs are potential drug targets. Oral administration of RR6, a pantothenone with nanomolar anti-VNN potency, completely inhibited plasma VNN activity in rats and showed favourable pharmacokinetics. Prolonged RR6 administration caused alterations of hepatic and plasma lipid concentrations upon fasting. VNN inhibitors were found to protect pantothenamides (pantetheine analogues with antibiotic activity) against breakdown by plasma VNN, thereby preserving their antibiotic activity. Combination of pantothenamides with a VNN inhibitor showed a strong activity against Staphylococcus aureus and Staphylococcus pneumoniae when assayed in the presence of 10% serum. Recent studies have reported plasma stable pantothenamides that were active against the malaria parasite Plasmodium falciparum. We conclude that VNN inhibitors and pantothenate derivatives that target enzymes in the CoA (coenzyme A) biosynthetic pathway may have potential use as novel drugs in infection, inflammation and metabolism

Postprandial hypotension in clinical geriatric patients and healthy elderly: prevalence related to patient selection and diagnostic criteria.

Contains fulltext : 89682.pdf (publisher's version ) (Open Access)The aims of this study were to find out whether Postprandial hypotension (PPH) occurs more frequently in patients admitted to a geriatric ward than in healthy elderly individuals, what the optimal interval between blood pressure measurements is in order to diagnose PPH and how often it is associated with symptoms.The result of this study indicates that PPH is present in a high number of frail elderly, but also in a few healthy older persons. Measuring blood pressure at least every 10 minutes for 60 minutes after breakfast will adequately diagnose PPH, defined as >20 mmHg systolic fall, in most patients. However with definition of PPH as >30 mmHg systolic fall, measuring blood pressure every 10 minutes will miss PPH in one of three patients. With the latter definition of PPH the presence of postprandial complaints is not associated with the existence of PPH