Jurnal Fakultas Ekonomi UM Metro (Universitas Muhammadiyah)
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A specific nutrient combination attenuates the reduced expression of PSD-95 in the proximal dendrites of hippocampal cell body layers in a mouse model of phenylketonuria
The inherited metabolic disease phenylketonuria (PKU) is characterized by increased concentrations of phenylalanine in the blood and brain, and as a consequence neurotransmitter metabolism, white matter, and synapse functioning are affected. A specific nutrient combination (SNC) has been shown to improve synapse formation, morphology and function. This could become an interesting new nutritional approach for PKU. To assess whether treatment with SNC can affect synapses, we treated PKU mice with SNC or an isocaloric control diet and wild-type (WT) mice with an isocaloric control for 12 weeks, starting at postnatal day 31. Immunostaining for post-synaptic density protein 95 (PSD-95), a post-synaptic density marker, was carried out in the hippocampus, striatum and prefrontal cortex. Compared to WT mice on normal chow without SNC, PKU mice on the isocaloric control showed a significant reduction in PSD-95 expression in the hippocampus, specifically in the granular cell layer of the dentate gyrus, with a similar trend seen in the cornus ammonis 1 (CA1) and cornus ammonis 3 (CA3) pyramidal cell layer. No differences were found in the striatum or prefrontal cortex. PKU mice on a diet supplemented with SNC showed improved expression of PSD-95 in the hippocampus. This study gives the first indication that SNC supplementation has a positive effect on hippocampal synaptic deficits in PKU mice.</p
Development of an iterative reconstruction method to overcome 2D detector low resolution limitations in MLC leaf position error detection for 3D dose verification in IMRT
The objective of this study was to introduce a new iterative method to reconstruct multi leaf collimator (MLC) positions based on low resolution ionization detector array measurements and to evaluate its error detection performance. The iterative reconstruction method consists of a fluence model, a detector model and an optimizer. Expected detector response was calculated using a radiotherapy treatment plan in combination with the fluence model and detector model. MLC leaf positions were reconstructed by minimizing differences between expected and measured detector response. The iterative reconstruction method was evaluated for an Elekta SLi with 10.0 mm MLC leafs in combination with the COMPASS system and the MatriXX Evolution (IBA Dosimetry) detector with a spacing of 7.62 mm. The detector was positioned in such a way that each leaf pair of the MLC was aligned with one row of ionization chambers. Known leaf displacements were introduced in various field geometries ranging from -10.0 mm to 10.0 mm. Error detection performance was tested for MLC leaf position dependency relative to the detector position, gantry angle dependency, monitor unit dependency, and for ten clinical intensity modulated radiotherapy (IMRT) treatment beams. For one clinical head and neck IMRT treatment beam, influence of the iterative reconstruction method on existing 3D dose reconstruction artifacts was evaluated. The described iterative reconstruction method was capable of individual MLC leaf position reconstruction with millimeter accuracy, independent of the relative detector position within the range of clinically applied MU's for IMRT. Dose reconstruction artifacts in a clinical IMRT treatment beam were considerably reduced as compared to the current dose verification procedure. The iterative reconstruction method allows high accuracy 3D dose verification by including actual MLC leaf positions reconstructed from low resolution 2D measurements.</p
Cluster Based Vector Attribute Filtering
Morphological attribute filters operate on images based on properties or attributes of connected components. Until recently, attribute filtering was based on a single global threshold on a scalar property to remove or retain objects. A single threshold struggles in case no single property or attribute value has a suitable, usually multi-modal, distribution. Vector-attribute filtering allows better description of characteristic features for 2D images. In this paper, we apply vector-attribute filtering to 3D and incorporate unsupervised pattern recognition, where connected components are classified based on the similarity of feature vectors. Using a single attribute allows multi-thresholding for attribute filters where more than two classes of structures of interest can be selected. In vector-attribute filters automatic clustering avoids the need for either setting very many attribute thresholds, or finding suitable class prototypes in 3D and setting a dissimilarity threshold. Explorative visualization reduces to visualizing and selecting relevant clusters. We show that the performance of these new filters is better than those of regular attribute filters in enhancement of objects in medical images
BFD-22 a new potential inhibitor of BRAF inhibits the metastasis of B16F10 melanoma cells and simultaneously increased the tumor immunogenicity
Benzofuroxan is an interesting ring system, which has shown a wide spectrum of biological responses against tumor cell lines. We investigated, herein, the antitumor effects of benzofuroxan derivatives (BFDs) in vitro and in a melanoma mouse model. Cytotoxic effects of twenty-two BFDs were determined by MIT assay. Effects of BFD-22 in apoptosis and cell proliferation were evaluated using Annexin V-FITC/PI and CFSE staining. In addition, the effects in the cell cycle were assessed. Flow cytometry, western blot, and fluorescence microscopy analysis were employed to investigate the apoptosis-related proteins and the BRAF signaling. Cell motility was also exploited through cell invasion and migration assays. Molecular docking approach was performed in order to verify the BFD-22 binding mode into the ATP catalytic site of BRAF kinase. Moreover, the BFD-22 antitumor effects were evaluated in a melanoma murine model using B16F10. BFD-22 was identified as a potential hit against melanoma cells. BFD-22 induced apoptosis and inhibited cell proliferation of B16F10 cells. BFD-22 has suppressed, indeed, the migratory and invasive behavior of B16F10 cells. Cyclin D1 and CDK4 expression were reduced leading to cell cycle arrest at G0/G1 phase. Of note, phosphorylation of BRAF at Ser338 was strongly down-regulated by BFD-22 in B16F10 cells. The accommodation/orientation into the binding site of BRAF was similar of BAY43-9006 (co-crystallized inhibitor of BRAF, sorafenib). Importantly, BFD-22 presented in vivo antimetastatic effects and showed better therapeutic efficacy than sorafenib and taxol. BFD-22 can be considered as a new lead compound and, then, can be helpful for the designing of novel drug candidates to treat melanoma. (C) 2016 Elsevier Inc. All rights reserved.</p
Outsourcing Immigration Control:A Comparison between Current US and EU Immigration Policy Measures
The fallacy of placing confidence in confidence intervals
Interval estimates – estimates of parameters that include an allowance for sampling uncertainty – have long been touted as a key component of statistical analyses. There are several kinds of interval estimates, but the most popular are confidence intervals (CIs): intervals that contain the true parameter value in some known proportion of repeated samples, on average. The width of confidence intervals is thought to index the precision of an estimate; CIs are thought to be a guide to which parameter values are plausible or reasonable; and the confidence coefficient of the interval (e.g., 95 %) is thought to index the plausibility that the true parameter is included in the interval. We show in a number of examples that CIs do not necessarily have any of these properties, and can lead to unjustified or arbitrary inferences. For this reason, we caution against relying upon confidence interval theory to justify interval estimates, and suggest that other theories of interval estimation should be used instead
Electrochemical redox cycling in a new nanogap sensor:Design and simulation
We propose a new geometry for nanogap electrochemical sensing devices. These devices consist of two closely spaced side-by-side electrodes which work under redox cycling conditions. Using finite element simulations, we investigate the effects of different geometric parameters on the redox cycling signal amplification to gain insight into the electrochemical sensing performance of the device design. This will allow optimizing the sensor performance of devices to be fabricated in the future. (C) 2015 Elsevier B.V. All rights reserved.</p
Market fundamentals, competition and natural-gas prices
After the liberalisation of the gas industry, trading hubs have emerged in Europe. Although these hubs appear to be liquid market places fostering gas-to-gas competition, the efficiency of the gas market remains a topic of interest as a fair share of gas is still traded through long-term contracts with prices linked to the oil price while the number of gas suppliers to the European market is limited. In order to assess the efficiency of the gas market, we analyse the day-ahead spot price at the Dutch gas hub over the period 2011-2014. We find that the oil price had a small positive impact on the gas price. Changes in the concentration on the supply side did not affect the movement in gas prices. The availability of gas in storages and the outside temperature negatively influenced the gas price. We also find that the gas price was related to the production of wind electricity. Overall, we conclude that the day-ahead gas prices are predominantly determined by gas-market fundamentals. Policies to further integrate gas markets within Europe may extend this gas-to-gas competition to a larger region
Home-making after stroke.:A qualitative study among Dutch stroke survivors
Stroke survivors may suffer from physical limitations as well as cognitive and behavioural difficulties. Many survivors work on their recovery in a rehabilitation clinic with the aim to return to their own home again. Since full recovery is often not feasible, they face the challenge of coming to terms with lasting effects of the stroke and of giving meaning to their home place again. Based on in-depth interviews with stroke survivors, we discuss the meaning of the home with respect to changed post-stroke identities. Our findings show how, for many participants, a formerly comfortable home becomes a space of struggle. Formerly stable bodily routines become time-consuming and demanding, reciprocal relationships with significant others change, often becoming unbalanced dependence. In conclusion, each stroke survivor faces a different struggle to accommodate a changed self in a house that does not feel like home anymore. These findings imply that stroke rehabilitation services need to address the individual and everyday challenges that stroke survivors and their families face at home, to improve their sense of home and well-being. (C) 2015 The Authors. Published by Elsevier Ltd.</p
Precision-cut human kidney slices as a model to elucidate the process of renal fibrosis
Chronic kidney disease is a major health concern, and experimental models bridging the gap between animal studies and clinical research are currently lacking. Here, we evaluated precision-cut kidney slices (PCKSs) as a potential model for renal disease. PCKSs were prepared from human cortical tissue obtained from tumor nephrectomies and cultured up to 96 hours. Morphology, cell viability, and metabolic functionality (ie, uridine 5'-diphospho-glucuronosyltransferase and transporter activity) were determined to assess the integrity of PCKSs. Furthermore, inflammatory and fibrosis-related gene expressions were characterized. Finally, to validate the model, renal fibrogenesis was induced using transforming growth factor beta 1 (TGF-beta 1). Preparation of PCKSs induced an inflammatory tissue response, whereas long-term incubation (96 hours) induced fibrogenesis as shown by an increased expression of collagen type 1A1 (COL1A1) and fibronectin 1 (FN1). Importantly, PCKSs remained functional for more than 48 hours as evidenced by active glucuronidation and phenolsulfonphthalein uptake. In addition, cellular diversity appeared to be maintained, yet we observed a clear loss of nephrin messenger RNA levels suggesting that our model might not be suitable to study the role of podocytes in renal pathology. Moreover, TGF-beta 1 exposure augmented fibrosis, as illustrated by an increased expression of multiple fibrosis markers including COL1A1, FN1, and alpha-smooth muscle actin. In conclusion, PCKSs maintain their renal phenotype during culture and appear to be a promising model to investigate renal diseases, for example, renal fibrosis. Moreover, the human origin of PCKSs makes this model very suitable for translational research.</p