Goldstone Bosons in Josephson Junctions

For a microscopic model of a Josephson junction the normal coordinates of the two junction Goldstone bosons are constructed and their dynamical spectrum is computed. The explicit dependence on the phase difference of the two superconductors is calculated

Kleine kinderen, kleine zorgen? Ondersteuningsbehoeften van ouders met zuigelingen in relatie tot ouder-, kind- en gezinskenmerken

status: publishe

Potential applications for sigma receptor ligands in cancer diagnosis and therapy

AbstractSigma receptors (sigma-1 and sigma-2) represent two independent classes of proteins. Their endogenous ligands may include the hallucinogen N,N-dimethyltryptamine (DMT) and sphingolipid-derived amines which interact with sigma-1 receptors, besides steroid hormones (e.g., progesterone) which bind to both sigma receptor subpopulations. The sigma-1 receptor is a ligand-regulated molecular chaperone with various ion channels and G-protein-coupled membrane receptors as clients. The sigma-2 receptor was identified as the progesterone receptor membrane component 1 (PGRMC1). Although sigma receptors are over-expressed in tumors and up-regulated in rapidly dividing normal tissue, their ligands induce significant cell death only in tumor tissue. Sigma ligands may therefore be used to selectively eradicate tumors. Multiple mechanisms appear to underlie cell killing after administration of sigma ligands, and the signaling pathways are dependent both on the type of ligand and the type of tumor cell. Recent evidence suggests that the sigma-2 receptor is a potential tumor and serum biomarker for human lung cancer and an important target for inhibiting tumor invasion and cancer progression. Current radiochemical efforts are focused on the development of subtype-selective radioligands for positron emission tomography (PET) imaging. Right now, the mostpromising tracers are [18F]fluspidine and [18F]FTC-146 for sigma-1 receptors and [11C]RHM-1 and [18F]ISO-1 for the sigma-2 subtype. Nanoparticles coupled to sigma ligands have shown considerable potential for targeted delivery of antitumor drugs in animal models of cancer, but clinical studies exploring this strategy in cancer patients have not yet been reported. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers

Shopping centre siting and modal choice in Belgium: a destination based analysis

Although modal split is only one of the elements considered in decision-making on new shopping malls, it remarkably often arises in arguments of both proponents and opponents. Today, this is also the case in the debate on the planned development of three major shopping malls in Belgium. Inspired by such debates, the present study focuses on the impact of the location of shopping centres on the travel mode choice of the customers. Our hypothesis is that destination-based variables such as embeddedness in the urban fabric, accessibility and mall size influence the travel mode choice of the visitors. Based on modal split data and location characteristics of seventeen existing shopping centres in Belgium, we develop a model for a more sustainable siting policy. The results show a major influence of the location of the shopping centre in relation to the urban form, and of the size of the mall. Shopping centres that are part of a dense urban fabric, measured through population density, are less car dependent. Smaller sites will attract more cyclists and pedestrians. Interestingly, our results deviate significantly from the figures that have been put forward in public debates on the shopping mall issue in Belgium

Other Radiopharmaceuticals for Imaging GEP‐NET

In GEP‐NETs, especially the catecholamine and serotonin biosynthetic pathways are upregulated. Therefore, increased biosynthesis of these specific amines in GEP‐NETs enables imaging with specific amine precursors. For the catecholamine pathway, 6‐18F ‐l‐3,4‐dihydroxyphenylalanine (18F‐DOPA) is available, while for the serotonin pathway, carbon‐11‐labeled 5‐hydroxy‐l‐tryptophan ([11C]‐5‐HTP) is available as tracer. 11C‐5‐HTP PET and 18F‐DOPA PET are excellent functional imaging techniques for evaluating patients with proven pancreatic islet cell tumors and carcinoids. For both tracers, the combination with CT further improves the detection rate of NET, which shows that performing PET scans with these tracers in PET/CT scanners is beneficial for patients.Since well‐differentiated GEP‐NETs generally have a low glucose metabolism, 18F‐fluorodexyglucose (18F‐FDG) PET scanning has limited value for the primary staging of patients with well‐differentiated GEP‐NETs. However, in patients with rapidly progressive disease, dedifferentiation of GEP‐NET tumors can lead to a higher glucose metabolism in tumor cells. In these patients, 18F‐FDG PET can be of benefit for tumor staging. Also, 18F‐FDG PET can be of value when other malignancies are suspected in patients with GEP‐NETs, since these patients experience a higher incidence of these malignancies compared to the general population.Nowadays, (GEP)‐NETs can also be imaged with 68Ga‐labeled analogues of somatostatin, which are also PET tracers. Advantages of 68Ga‐labeled somatostatin analogues are the relatively easy generator‐based synthesis and the possibility to evaluate whether peptide (somatostatin) receptor radionuclide therapy (PRRT) for NETs can be considered

Buckling of scroll waves

A scroll wave in a sufficiently thin layer of an excitable medium with negative filament tension can be stable nevertheless due to filament rigidity. Above a certain critical thickness of the medium, such scroll wave will have a tendency to deform into a buckled, precessing state. Experimentally this will be seen as meandering of the spiral wave on the surface, the amplitude of which grows with the thickness of the layer, until a break-up to scroll wave turbulence happens. We present a simplified theory for this phenomenon and illustrate it with numerical examples.Comment: 4 pages main text + 5 pages appendix, 4+2 figures and a movie, as accepted by Phys Rev Letters 2012/09/2

Parkinson's disease-related perfusion and glucose metabolic brain patterns identified with PCASL-MRI and FDG-PET imaging

AbstractIntroductionUnder normal conditions, the spatial distribution of resting cerebral blood flow and cerebral metabolic rate of glucose are closely related. A relatively new magnetic resonance (MR) technique, pseudo-continuous arterial spin labeling (PCASL), can be used to measure regional brain perfusion. We identified a Parkinson's disease (PD)-related perfusion and metabolic covariance pattern in the same patients using PCASL and FDG-PET imaging and assessed (dis)similarities in the disease-related pattern between perfusion and metabolism in PD patients.MethodsNineteen PD patients and seventeen healthy controls underwent [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. Of 14 PD patients and all healthy controls PCASL-MRI could be obtained. Data were analyzed using scaled subprofile model/principal component analysis (SSM/PCA).ResultsUnique Parkinson's disease-related perfusion and metabolic covariance patterns were identified using PCASL and FDG-PET in the same patients. The PD-related metabolic covariance brain pattern is in high accordance with previously reports. Also our disease-related perfusion pattern is comparable to the earlier described perfusion pattern. The most marked difference between our perfusion and metabolic patterns is the larger perfusion decrease in cortical regions including the insula.ConclusionWe identified PD-related perfusion and metabolic brain patterns using PCASL and FDG-PET in the same patients which were comparable with results of existing research. In this respect, PCASL appears to be a promising addition in the early diagnosis of individual parkinsonian patients

Systems Approach Reveals Nuclear Factor Erythroid 2-Related Factor 2/Protein Kinase R Crosstalk in Human Cutaneous Leishmaniasis

Leishmania parasites infect macrophages, causing a wide spectrum of human diseases, from cutaneous to visceral forms. In search of novel therapeutic targets, we performed comprehensive in vitro and ex vivo mapping of the signaling pathways upstream and downstream of antioxidant transcription factor [nuclear factor erythroid 2-related factor 2 (Nrf2)] in cutaneous leishmaniasis (CL), by combining functional assays in human and murine macrophages with a systems biology analysis of in situ (skin biopsies) CL patient samples. First, we show the PKR pathway controls the expression and activation of Nrf2 in Leishmania amazonensis infection in vitro. Nrf2 activation also required PI3K/Akt signaling and autophagy mechanisms. Nrf2- or PKR/Akt-deficient macrophages exhibited increased levels of ROS/RNS and reduced expression of Sod1 Nrf2-dependent gene and reduced parasite load. L. amazonensis counteracted the Nrf2 inhibitor Keap1 through the upregulation of p62 via PKR. This Nrf2/Keap1 observation was confirmed in situ in skin biopsies from Leishmania-infected patients. Next, we explored the ex vivo transcriptome in CL patients, as compared to healthy controls. We found the antioxidant response element/Nrf2 signaling pathway was significantly upregulated in CL, including downstream target p62. In silico enrichment analysis confirmed upstream signaling by interferon and PI3K/Akt, and validated our in vitro findings. Our integrated in vitro, ex vivo, and in silico approach establish Nrf2 as a central player in human cutaneous leishmaniasis and reveal Nrf2/PKR crosstalk and PI3K/Akt pathways as potential therapeutic targets

Maternal Sociodemographic Factors Are Associated With Methylphenidate Initiation in Children in the Netherlands: A Population-Based Study

Multiple factors may contribute to the decision to initiate methylphenidate treatment in children such as maternal sociodemographic factors of which relatively little is known. The objective was to investigate the association between these factors and methylphenidate initiation. The study population included 4243 children from the Generation R Study in the Netherlands. Maternal sociodemographic characteristics were tested as determinants of methylphenidate initiation through a timedependent Cox regression analysis. Subsequently, we stratifed by mother-reported ADHD symptoms (present in 4.2% of the study population). When ADHD symptoms were absent, we found that girls (adjusted HR 0.25, 95%CI 0.16–0.39) and children born to a mother with a non-western ethnicity (compared to Dutch-Caucasian) (adjusted HR 0.42, 95%CI 015–0.68) were less likely to receive methylphenidate. They were more likely to receive methylphenidate when their mother completed a low (adjusted HR 2.29, 95%CI 1.10–4.77) or secondary (adjusted HR 1.71, 95%CI 1.16–2.54) education. In conclusion, boys and children born to a mother of Dutch-Caucasian ethnicity were more likely to receive methylphenidate, irrespective of the presence of ADHD symptoms