| 11. |
- Ferreira, Ruben, 1982, et al.
(author)
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Design, Synthesis and Inhibitory Activity of Photoswitchable RET Kinase Inhibitors.
- 2015
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
-
Journal article (peer-reviewed)abstract
- REarranged during Transfection (RET) is a transmembrane receptor tyrosine kinase required for normal development and maintenance of neurons of the central and peripheral nervous systems. Deregulation of RET and hyperactivity of the RET kinase is intimately connected to several types of human cancers, most notably thyroid cancers, making it an attractive therapeutic target for small-molecule kinase inhibitors. Novel approaches, allowing external control of the activity of RET, would be key additions to the signal transduction toolbox. In this work, photoswitchable RET kinase inhibitors based on azo-functionalized pyrazolopyrimidines were developed, enabling photonic control of RET activity. The most promising compound displays excellent switching properties and stability with good inhibitory effect towards RET in cell-free as well as live-cell assays and a significant difference in inhibitory activity between its two photoisomeric forms. As the first reported photoswitchable small-molecule kinase inhibitor, we consider the herein presented effector to be a significant step forward in the development of tools for kinase signal transduction studies with spatiotemporal control over inhibitor concentration in situ.
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| 12. |
- Gelder, Marion E Meijer-Van, et al.
(author)
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Long-term survival of patients with CLL after allogeneic transplantation : A report from the European Society for Blood and Marrow Transplantation
- 2017
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In: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 52:3, s. 372-380
-
Journal article (peer-reviewed)abstract
- Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients.
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| 13. |
- Guzmán, Daniel, et al.
(author)
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Preparation of hydrophilic poly(3-hydroxybutyrate) macroporous scaffolds through enzyme-mediated modifications
- 2011
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In: Journal of Bioactive and Compatible Polymers. - : SAGE Publications. - 0883-9115 .- 1530-8030. ; 26:5, s. 452-463
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Journal article (peer-reviewed)abstract
- Scaffolds made from poly(3-hydroxybutyrate) were prepared by thermally induced phase separation from solutions in dioxane at temperatures above (23 degrees C) or below the freezing point of the solvent. At 23 degrees C, gelation occured with nano-fibrous network formation. The scaffolds prepared at -12 degrees C and -25 degrees C exhibited a highly porous morphology, with pores in the range of 3-25 mu m, caused by freezing of dioxane. The macroporous scaffolds, prepared at -12 degrees C, were treated with lipase to generate functional groups to which gelatin and glucosamine, respectively, were chemically coupled. The modified scaffolds had lower molecular weight, higher water content, lower melting temperature, and enthalpy. Cultivation of human embryonic fibroblasts on the macroporous scaffolds confirmed that the cells proliferated and adhered to the materials.
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| 14. |
- Jacobo-Martin, Alejandra, et al.
(author)
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Resilient moth-eye nanoimprinted antireflective and self-cleaning TiO2 sputter-coated PMMA films
- 2022
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In: Applied Surface Science. - : Elsevier. - 0169-4332 .- 1873-5584. ; 585
-
Journal article (peer-reviewed)abstract
- Moth-eye nanostructures are amongst the most remarkable surfaces in nature because of their multi-functionality including antireflection, self-cleaning and bactericidal ability. Moth-eye surfaces consist of subwavelength arrays of tapered nanostructures, which are challenging to reproduce artificially. Nanoimprint lithography is probably one of the most suited technologies for this purpose. However, the poor mechanical resilience and durability of the polymeric nanocones when exposed to the environment, hinders their use in actual applications. To overcome these limitations, this work demonstrates the use of a thin oxide coating over the polymer moth-eye features imprinted on poly methyl methacrylate (PMMA) films. Particularly TiO2 conformal thin film coatings are deposited by unipolar pulsed dc magnetron sputtering over the antireflective nanopatterns acting as encapsulant. The coating, while preserving the antireflective properties, protects the nanostructures against mechanical scratching and improves substantially their thermal stability to over 250 ?. Furthermore, the TiO2 layer provides additional photoinduced self-cleaning functionality and at the same time it protects the matrix from UV photodegradation. The robust and durable antireflective surfaces developed here may find application on solar cells covers, flat panel displays or on optical components.
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| 15. |
- Jonsson, Stefan, et al.
(author)
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Synthesis of 2-pyridone-fused 2,2 '-bipyridine derivatives. An unexpectedly complex solid state structure of 3,6-dimethyl-9H-4,5,9-triazaphenanthren-10-one
- 2005
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In: Organic and Biomolecular Chemistry. - : Royal Society of Chemistry (RSC). - 1477-0539. ; 3:6, s. 996-1001
-
Journal article (peer-reviewed)abstract
- 2- Pyridone- fused 2,2'- bipyridine derivatives 1a and 1b were synthesised. X- Ray diffraction analysis of 1b revealed a highly complex solid state structure with a disordered molecule imbedded in a channel structure formed by a centrosymmetric lattice of hexagonally packed, hydrogen bonded columns. The columns are assembled from three symmetry independent molecules. Dimerisation of the self- complementary cis- amide hydrogen bond motif is overridden by the fulfilment of the proton coordination ability of the phenanthroline nitrogens in accordance with Etter's rules of hydrogen bond priorities.
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| 16. |
- Kumar, Nallani Vijay, et al.
(author)
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Arsenic Directly Binds to and Activates the Yeast AP-1-Like Transcription Factor Yap8.
- 2016
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In: Molecular and cellular biology. - 1098-5549. ; 36:6, s. 913-22
-
Journal article (peer-reviewed)abstract
- The AP-1-like transcription factor Yap8 is critical for arsenic tolerance in the yeast Saccharomyces cerevisiae. However, the mechanism by which Yap8 senses the presence of arsenic and activates transcription of detoxification genes is unknown. Here we demonstrate that Yap8 directly binds to trivalent arsenite [As(III)] in vitro and in vivo and that approximately one As(III) molecule is bound per molecule of Yap8. As(III) is coordinated by three sulfur atoms in purified Yap8, and our genetic and biochemical data identify the cysteine residues that form the binding site as Cys132, Cys137, and Cys274. As(III) binding by Yap8 does not require an additional yeast protein, and Yap8 is regulated neither at the level of localization nor at the level of DNA binding. Instead, our data are consistent with a model in which a DNA-bound form of Yap8 acts directly as an As(III) sensor. Binding of As(III) to Yap8 triggers a conformational change that in turn brings about a transcriptional response. Thus, As(III) binding to Yap8 acts as a molecular switch that converts inactive Yap8 into an active transcriptional regulator. This is the first report to demonstrate how a eukaryotic protein couples arsenic sensing to transcriptional activation.
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| 17. |
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| 18. |
- Lidskog, Anna, et al.
(author)
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Experimental and Computational Models for Side Chain Discrimination in Peptide–Protein Interactions
- 2021
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In: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 27:42, s. 10883-10897
-
Journal article (peer-reviewed)abstract
- A bis(18-crown-6) Tröger's base receptor and 4-substituted hepta-1,7-diyl bisammonium salt ligands have been used as a model system to study the interactions between non-polar side chains of peptides and an aromatic cavity of a protein. NMR titrations and NOESY/ROESY NMR spectroscopy were used to analyze the discrimination of the ligands by the receptor based on the substituent of the ligand, both quantitatively (free binding energies) and qualitatively (conformations). The analysis showed that an all-anti conformation of the heptane chain was preferred for most of the ligands, both free and when bound to the receptor, and that for all of the receptor-ligand complexes, the substituent was located inside or partly inside of the aromatic cavity of the receptor. We estimated the free binding energy of a methyl- and a phenyl group to an aromatic cavity, via CH-π, and combined aromatic CH-π and π-π interactions to be −1.7 and −3.3 kJ mol−1, respectively. The experimental results were used to assess the accuracy of different computational methods, including molecular mechanics (MM) and density functional theory (DFT) methods, showing that MM was superior.
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| 19. |
- Murari, A., et al.
(author)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
-
In: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
-
Journal article (peer-reviewed)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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| 20. |
- Nespolo, Roberto F., et al.
(author)
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Aerobic power and flight capacity in birds: a phylogenetic test of the heart-size hypothesis
- 2018
-
In: Journal of Experimental Biology. - : COMPANY OF BIOLOGISTS LTD. - 0022-0949 .- 1477-9145. ; 221:1
-
Journal article (peer-reviewed)abstract
- Flight capacity is one of the most important innovations in animal evolution; it only evolved in insects, birds, mammals and the extinct pterodactyls. Given that powered flight represents a demanding aerobic activity, an efficient cardiovascular system is essential for the continuous delivery of oxygen to the pectoral muscles during flight. It is well known that the limiting step in the circulation is stroke volume (the volume of blood pumped from the ventricle to the body during each beat), which is determined by the size of the ventricle. Thus, the fresh mass of the heart represents a simple and repeatable anatomical measure of the aerobic power of an animal. Although several authors have compared heart masses across bird species, a phylogenetic comparative analysis is still lacking. By compiling heart sizes for 915 species and applying several statistical procedures controlling for body size and/or testing for adaptive trends in the dataset (e.g. model selection approaches, phylogenetic generalized linear models), we found that (residuals of) heart size is consistently associated with four categories of flight capacity. In general, our results indicate that species exhibiting continuous hovering flight (i.e. hummingbirds) have substantially larger hearts than other groups, species that use flapping flight and gliding show intermediate values, and that species categorized as poor flyers show the smallest values. Our study reveals that on a broad scale, routine flight modes seem to have shaped the energetic requirements of birds sufficiently to be anatomically detected at the comparative level.
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