| 1. |
- In ’t Veld, Sjors G.J.G., et al.
(author)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
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In: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Journal article (peer-reviewed)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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| 2. |
- Babazadeh, Roja, et al.
(author)
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Syntaxin 5 Is Required for the Formation and Clearance of Protein Inclusions during Proteostatic Stress
- 2019
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 28:8
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Journal article (peer-reviewed)abstract
- Spatial sorting to discrete quality control sites in the cell is a process harnessing the toxicity of aberrant proteins. We show that the yeast t-snare phosphoprotein syntaxin5 (Sed5) acts as a key factor in mitigating proteotoxicity and the spatial deposition and clearance of IPOD (insoluble protein deposit) inclusions associates with the disaggregase Hsp104. Sed5 phosphorylation promotes dynamic movement of COPII-associated Hsp104 and boosts disaggregation by favoring anterograde ER-to-Golgi trafficking. Hsp104-associated aggregates co-localize with Sed5 as well as components of the ER, trans Golgi network, and endocytic vesicles, transiently during proteostatic stress, explaining mechanistically how misfolded and aggregated proteins formed at the vicinity of the ER can hitchhike toward vacuolar IPOD sites. Many inclusions become associated with mitochondria in a HOPS/vCLAMP-dependent manner and co-localize with Vps39 (HOPS/vCLAMP) and Vps13, which are proteins providing contacts between vacuole and mitochondria. Both Vps39 and Vps13 are required also for efficient Sed5-dependent clearance of aggregates.
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| 3. |
- Charrier, D. S. H., et al.
(author)
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Bimolecular recombination in ambipolar organic field effect transistors
- 2009
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In: Organic electronics. - : Elsevier. - 1566-1199 .- 1878-5530. ; 10:5, s. 994-997
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Journal article (peer-reviewed)abstract
- In ambipolar organic field effect transistors (OFET) the shape of the channel potential is intimately related to the recombination zone width W, and hence to the electron-hole recombination strength. Experimentally, the recombination profile can be assessed by scanning Kelvin probe microscopy (SKPM). However, surface potentials as measured by SKPM are distorted due to spurious capacitive couplings. Here, we present a (de)convolution method with an experimentally calibrated transfer function to reconstruct the actual surface potential from a measured SKPM response and vice versa. Using this scheme, we find W = 0.5 mu m for a nickel dithiolene OFET, which translates into a recombination rate that is two orders of magnitude below the value expected for Langevin recombination. (C) 2009 Elsevier B.V. All rights reserved.
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| 4. |
- Kemerink, M., et al.
(author)
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On the width of the recombination zone in ambipolar organic field effect transistors
- 2008
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In: Applied Physics Letters. - : American Institute of Physics (AIP). - 0003-6951 .- 1077-3118. ; 93:3
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Journal article (peer-reviewed)abstract
- The performance of organic light emitting field effect transistors is strongly influenced by the width of the recombination zone. We present an analytical model for the recombination profile. By assuming Langevin recombination, the recombination zone width W is found to be given by W = root 4.34d delta, with d and delta the gate dielectric and accumulation layer thicknesses, respectively. The model compares favorably to both numerical calculations and measured surface potential profiles of an actual ambipolar device. (C) 2008 American Institute of Physics.
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| 5. |
- Mathijssen, Simon G. J., et al.
(author)
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Manipulating the local light emission in organic light-emitting diodes by using patterned self-assembled monolayers
- 2008
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In: Advanced Materials. - : Wiley-VCH Verlag. - 0935-9648 .- 1521-4095. ; 20:14, s. 2703-
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Journal article (peer-reviewed)abstract
- Patterned organic light-emitting diodes are fabricated by using microcontactDrinted self-assembled monolayers on a gold anode (see background figure). Molecules with dipole moments in opposite directions result in an increase or a decrease of the local work function (foreground picture), providing a direct handle on charge injection and enabling local modification of the light emission
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| 6. |
- Mathijssen, Simon G. J., et al.
(author)
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Monolayer coverage and channel length set the mobility in self-assembled monolayer field-effect transistors
- 2009
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In: Nature Nanotechnology. - : Nature Publishing Group. - 1748-3387 .- 1748-3395. ; 4:10, s. 674-680
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Journal article (peer-reviewed)abstract
- The mobility of self-assembled monolayer field-effect transistors (SAMFETs) traditionally decreases dramatically with increasing channel length. Recently, however, SAMFETs using liquid-crystalline molecules have been shown to have bulk-like mobilities that are virtually independent of channel length. Here, we reconcile these scaling relations by showing that the mobility in liquid crystalline SAMFETs depends exponentially on the channel length only when the monalayer is incomplete. We explain this dependence both numerically and analytically, and show that charge transport is not affected by carrier injection, grain boundaries or conducting island size. At partial coverage, that is when the monolayer is incomplete, liquid-crystalline SAMFETs thus form a unique model system to study size-dependent conductance originating from charge percolation in two dimensions.
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| 7. |
- Sharma, A., et al.
(author)
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Proton migration mechanism for operational instabilities in organic field-effect transistors
- 2010
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In: Physical Review B. Condensed Matter and Materials Physics. - : American Physical Society. - 1098-0121 .- 1550-235X. ; 82:7
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Journal article (peer-reviewed)abstract
- Organic field-effect transistors exhibit operational instabilities involving a shift of the threshold gate voltage when a gate bias is applied. For a constant gate bias the threshold voltage shifts toward the applied gate bias voltage, an effect known as the bias-stress effect. Here, we report on a detailed experimental and theoretical study of operational instabilities in p-type transistors with silicon-dioxide gate dielectric both for a constant as well as for a dynamic gate bias. We associate the instabilities with a reversible reaction in the organic semiconductor in which holes are converted into protons in the presence of water and a reversible migration of these protons into the gate dielectric. We show how redistribution of charge between holes in the semiconductor and protons in the gate dielectric can consistently explain the experimental observations. Furthermore, we show how a shorter period of application of a gate bias leads to a faster backward shift of the threshold voltage when the gate bias is removed. The proposed mechanism is consistent with the observed acceleration of the bias-stress effect with increasing humidity, increasing temperature, and increasing energy of the highest molecular orbital of the organic semiconductor.
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| 8. |
- Smits, Edsger C. P., et al.
(author)
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Bottom-up organic integrated circuits
- 2008
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 455:7215, s. 956-959
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Journal article (peer-reviewed)abstract
- Self- assembly - the autonomous organization of components into patterns and structures(1) - is a promising technology for the mass production of organic electronics. Making integrated circuits using a bottom- up approach involving self- assembling molecules was proposed(2) in the 1970s. The basic building block of such an integrated circuit is the self- assembled- monolayer field- effect transistor ( SAMFET), where the semiconductor is a monolayer spontaneously formed on the gate dielectric. In the SAMFETs fabricated so far, current modulation has only been observed in submicrometre channels(3-5), the lack of efficient charge transport in longer channels being due to defects and the limited intermolecular pi-pi coupling between the molecules in the self-assembled monolayers. Low field- effect carrier mobility, low yield and poor reproducibility have prohibited the realization of bottom- up integrated circuits. Here we demonstrate SAMFETs with long- range intermolecular pi - pi coupling in the monolayer. We achieve dense packing by using liquid- crystalline molecules consisting of a pi- conjugated mesogenic core separated by a long aliphatic chain from a monofunctionalized anchor group. The resulting SAMFETs exhibit a bulk- like carrier mobility, large current modulation and high reproducibility. As a first step towards functional circuits, we combine the SAMFETs into logic gates as inverters; the small parameter spread then allows us to combine the inverters into ring oscillators. We demonstrate real logic functionality by constructing a 15- bit code generator in which hundreds of SAMFETs are addressed simultaneously. Bridging the gap between discrete monolayer transistors and functional self-assembled integrated circuits puts bottom- up electronics in a new perspective.
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| 9. |
- Spijkman, M., et al.
(author)
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Monolayer dual gate transistors with a single charge transport layer
- 2010
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In: Applied Physics Letters. - : American Institute of Physics (AIP). - 0003-6951 .- 1077-3118. ; 96:14
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Journal article (peer-reviewed)abstract
- A dual gate transistor was fabricated using a self-assembled monolayer as the semiconductor. We show the possibility of processing a dielectric on top of the self-assembled monolayer without deteriorating the device performance. The two gates of the transistor accumulate charges in the monomolecular transport layer and artifacts caused by the semiconductor thickness are negated. We investigate the electrical transport in a dual gate self-assembled monolayer field-effect transistor and present a detailed analysis of the importance of the contact geometry in monolayer field-effect transistors.
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| 10. |
- Van Eunen, K., et al.
(author)
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Measuring enzyme activities under standardized in-vivo like conditions for systems biology
- 2010
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In: FEBS Journal. - : Wiley. - 1742-4658 .- 1742-464X. ; 277:3, s. 749-760
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Journal article (peer-reviewed)abstract
- Realistic quantitative models require data from many laboratories. Therefore, standardization of experimental systems and assay conditions is crucial. Moreover, standards should be representative of the in vivo conditions. However, most often, enzyme-kinetic parameters are measured under assay conditions that yield the maximum activity of each enzyme. In practice, this means that the kinetic parameters of different enzymes are measured in different buffers, at different pH values, with different ionic strengths, etc. In a joint effort of the Dutch Vertical Genomics Consortium, the European Yeast Systems Biology Network and the Standards for Reporting Enzymology Data Commission, we have developed a single assay medium for determining enzyme-kinetic parameters in yeast. The medium is as close as possible to the in vivo situation for the yeast Saccharomyces cerevisiae, and at the same time is experimentally feasible. The in vivo conditions were estimated for S. cerevisiae strain CEN. PK113-7D grown in aerobic glucose-limited chemostat cultures at an extracellular pH of 5.0 and a specific growth rate of 0.1 h(-1). The cytosolic pH and concentrations of calcium, sodium, potassium, phosphorus, sulfur and magnesium were determined. On the basis of these data and literature data, we propose a defined in vivo-like medium containing 300 mm potassium, 50 mm phosphate, 245 mm glutamate, 20 mm sodium, 2 mm free magnesium and 0.5 mm calcium, at a pH of 6.8. The V(max) values of the glycolytic and fermentative enzymes of S. cerevisiae were measured in the new medium. For some enzymes, the results deviated conspicuously from those of assays done under enzyme-specific, optimal conditions
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