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- Iancu, C. V., et al.
(author)
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GLUT3 inhibitor discovery through in silico ligand screening and in vivo validation in eukaryotic expression systems
- 2022
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Journal article (peer-reviewed)abstract
- The passive transport of glucose and related hexoses in human cells is facilitated by members of the glucose transporter family (GLUT, SLC2 gene family). GLUT3 is a high-affinity glucose transporter primarily responsible for glucose entry in neurons. Changes in its expression have been implicated in neurodegenerative diseases and cancer. GLUT3 inhibitors can provide new ways to probe the pathophysiological role of GLUT3 and tackle GLUT3-dependent cancers. Through in silico screening of an ~ 8 million compounds library against the inward- and outward-facing models of GLUT3, we selected ~ 200 ligand candidates. These were tested for in vivo inhibition of GLUT3 expressed in hexose transporter-deficient yeast cells, resulting in six new GLUT3 inhibitors. Examining their specificity for GLUT1-5 revealed that the most potent GLUT3 inhibitor (G3iA, IC50 ~ 7µM) was most selective for GLUT3, inhibiting less strongly only GLUT2 (IC50 ~ 29µM). None of the GLUT3 inhibitors affected GLUT5, three inhibited GLUT1 with equal or twofold lower potency, and four showed comparable or two- to fivefold better inhibition of GLUT4. G3iD was a pan-Class 1 GLUT inhibitor with the highest preference for GLUT4 (IC50 ~ 3.9µM). Given the prevalence of GLUT1 and GLUT3 overexpression in many cancers and multiple myeloma’s reliance on GLUT4, these GLUT3 inhibitors may discriminately hinder glucose entry into various cancer cells, promising novel therapeutic avenues in oncology. © 2022, The Author(s).
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- Ivády, Viktor, et al.
(author)
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Pressure and temperature dependence of the zero-field splitting in the ground state of NV centers in diamond: A first-principles study
- 2014
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In: Physical Review B. Condensed Matter and Materials Physics. - : American Physical Society. - 1098-0121 .- 1550-235X. ; 90:23, s. 235205-
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Journal article (peer-reviewed)abstract
- Nitrogen-vacancy centers in diamond (NV) attract great attention because they serve as a tool in many important applications. The NV center has a polarizable spin S = 1 ground state and its spin state can be addressed by optically detected magnetic resonance (ODMR) techniques. The m(S) = 0 and m(S) = +/- 1 spin levels of the ground state are separated by about 2.88 GHz in the absence of an external magnetic field or any other perturbations. This zero-field splitting (ZFS) can be probed by ODMR. As this splitting changes as a function of pressure and temperature, the NV center might be employed as a sensor operating at the nanoscale. Therefore, it is of high importance to understand the intricate details of the pressure and temperature dependence of this splitting. Here we present an ab initio theory of the ZFS of the NV center as a function of external pressure and temperature including detailed analysis on the contributions of macroscopic and microscopic effects. We found that the pressure dependence is governed by the change in the distance between spins as a consequence of the global compression and the additional local structural relaxation. The local structural relaxation contributes to the change of ZFS with the same magnitude as the global compression. In the case of temperature dependence of ZFS, we investigated the effect of macroscopic thermal expansion as well as the consequent change of the microscopic equilibrium positions. We could conclude that theses effects are responsible for about 15% of the observed decrease of ZFS.
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- Lisova, Elena, et al.
(author)
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Risk Evaluation of an ARP Poisoning Attack on Clock Synchronization for Industrial Applications
- 2016
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In: Proceedings of the IEEE International Conference on Industrial Technology. ; , s. 872-878
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Conference paper (peer-reviewed)abstract
- Nowadays, mixed wireless and wired networks are used everywhere in everyday life, including in industry where they often support time-critical applications. Industrial applications with high precision requirements are subject to real-time constraints, and thus one of the main assets, regardless of application area, is clock synchronization. Considering such networks, synchronization is the first thing to secure against a possible malicious adversary. In this paper, we consider ARP poisoning as a possible technique to disrupt clock synchronization and evaluate the effects of such an attack on the IEEE 1588 standard. We describe possible ways of performing ARP poisoning to disrupt synchronization and survey several mitigation techniques and their applicability within the industrial application area.
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- Naessen, Sabine, et al.
(author)
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Women with bulimia nervosa exhibit attenuated secretion of glucagon-like peptide 1, pancreatic polypeptide, and insulin in response to a meal
- 2011
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In: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 94:4, s. 967-972
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Journal article (peer-reviewed)abstract
- Background: The eating disorder bulimia nervosa (BN) is characterized by frequent episodes of binge eating, followed regularly by inappropriate compensatory behavior, such as self-induced vomiting. Objective: The current investigation was designed to examine possible alterations in the secretion of the gastrointestinal satiety peptides glucagon-like peptide 1 (GLP-1) and pancreatic polypeptide (PP) in women with BN. Design: Twenty-one women with BN and 17 healthy control subjects of comparable age and BMI were recruited. After fasting overnight, the subjects provided blood samples during ingestion of a standardized meal and self-rated their appetite on a visual analog scale. Fasting and meal-related secretion of the incretin GLP-1 and the meal-related feedback signal PP and insulin and glucose as indicators of the metabolic homeostasis were analyzed. Results: Women with BN had significantly lower fasting and postprandial serum concentrations of GLP-1 (P < 0.01) and PP (P < 0.05) than did the control subjects. Furthermore, both the basal (P < 0.001) and peak (P < 0.05) concentrations of insulin were significantly attenuated in the bulimic subjects, whereas glucose concentrations were normal. As a consequence, the bulimic homeostasis model assessment of insulin index values were also lower (P < 0.001). Conclusions: Women with BN secrete abnormally low amounts of GLP-1 and PP, possibly because of the adaption to large meals in the form of enlarged gastric capacity and reduced muscle tone in the gastric wall. Attenuated secretion of these gastrointestinal satiety peptides may play a role in the maintenance of bulimic behavior.
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