1,480 research outputs found
Ab-initio quantum transport simulation of self-heating in single-layer 2-D materials
Through advanced quantum mechanical simulations combining electron and phonon
transport from first-principles self-heating effects are investigated in n-type
transistors with a single-layer MoS2, WS2, and black phosphorus as channel
materials. The selected 2-D crystals all exhibit different phonon-limited
mobility values, as well as electron and phonon properties, which has a direct
influence on the increase of their lattice temperature and on the power
dissipated inside their channel as a function of the applied gate voltage and
electrical current magnitude. This computational study reveals (i) that
self-heating plays a much more important role in 2-D materials than in Si
nanowires, (ii) that it could severely limit the performance of 2-D devices at
high current densities, and (iii) that black phosphorus appears less sensitive
to this phenomenon than transition metal dichalcogenides
Multireactive PV-electrophiles for cysteine directed bioconjugation
In der vorliegenden Arbeit werden drei neue Klassen von modular zugĂ€nglichen Elektrophilen fĂŒr die Biokonjugation von Cystein vorgestellt.
Diethynyl-phosphinate (DPs) wurden als bisreaktive Elektrophile fĂŒr die cysteinselektive Markierung von Peptiden, Proteinen und Antikörpern entwickelt. In diesen MolekĂŒlen können beide elektronenarmen Dreifachbindungen unter physiologischen Bedingungen mit Thiol-Nukleophilen reagieren und die erhaltenen Konjugate sind in menschlichem Plasma und in Gegenwart groĂer Mengen an reduziertem Glutathion stabil. DarĂŒber hinaus wurden DPs in der selektiven Herstellung verschiedener Protein-(Doppel)-Konjugate angewandt. Neben der klassischen Proteinmodifikation können DPs auch zur kovalenten VerbrĂŒckung der DisulfidbrĂŒcken von Antikörpern eingesetzt werden.
Weiters wurde mit Hilfe von Dichtefunktionaltheorie-Berechnungen werden Ethinyl-triazolyl-phosphinate (ETP) als eine neue Klasse hochreaktiver Elektrophile fĂŒr die Cystein-Biokonjugation entdeckt. Die Berechnungen zeigen, dass sowohl die elektronenziehenden als auch die Ï-Elektronen donierenden Eigenschaften des Triazolrings die ReaktivitĂ€t erhöhen. Vor allem aber wird gezeigt, dass ETP-Elektrophile ĂŒber die chemoselektive Cu(I)-katalysierte Azid-Alkin-Cycloaddition in ein azidhaltiges MolekĂŒl eingebaut werden können. Da diese Reaktion problemlos in wĂ€ssrigen Puffersystemen ablĂ€uft, konnte eine Vielzahl funktioneller Elektrophile, einschlieĂlich elektrophiler Peptide und Proteine, aus DPs erzeugt werden.
SchlieĂlich wurden Diethinylphosphinoxide als chemoselektive Reagenzien zur DisulfidvererbrĂŒckung untersucht. Insbesondere Diethinyl-Triazolyl-Phosphinoxide (DTP) sind vielversprechende Kandidaten, da sie die modulare Synthese von ETP-Elektrophilen mit den beiden reaktiven Gruppen in DPs kombinieren. Die FĂ€higkeit der DTP-Reagenzien, Disulfide zu verbrĂŒcken, wurde durch die Bildung mehrerer funktioneller Antikörperkonjugate gezeigt.The present work introduces three new classes of modular accessible electrophiles for cysteine bioconjugation.
Diethynyl-phosphinates (DPs) were developed as bisreactive electrophiles for the cysteine-selective modification of peptides, proteins and antibodies. Both electrophilic alkynes can react with thiol-nucleophiles under physiological conditions. The corresponding double-conjugates are stable in human plasma and in the presence of a large excess reduced glutathione. Furthermore, the general applicability of diethynyl phosphinates for cysteine selective bioconjugation was established by the generation of various protein-(double)-conjugates and their application in cell experiments. Additionally, DPs can be employed to covalently rebridge the interchain disulfides of therapeutically relevant IgG1 antibodies.
Furthermore, with the help of density functional theory based calculations, ethynyl-triazolyl-phosphinates (ETP) were discovered as a new class of highly reactive electrophilic warheads for cysteine bioconjugation. According to the calculations, both the electron withdrawing as well as the Ï-electron donating properties of the triazole-ring enhance the reactivity of the electrophile. Most importantly, it was demonstrated that ETP electrophiles can be incorporated into a given azide containing molecule via the chemoselective CuI-catalyzed azide alkyne cycloaddition. ETP-reagents were used to obtain functional peptide-, protein- and antibody-conjugates, as well as site-specifically linked diubiquitins.
Finally, diethynyl phosphine oxides were explored as chemoselective reagents for disulfide rebridging. Especially diethynyl-triazolyl-phosphine oxides (DTP) are promising candidates since they combine the modular synthesis of ETP-electrophiles with the two reactive groups present in diethynyl phosphinates. The capability of DTP-reagents to rebridged disulfides was proven by the formation several functional antibody conjugates
Radiation dose optimization in pediatric temporal bone computed tomography: influence of tube tension on image contrast and image quality
Introduction: The purpose of this experimental study was to investigate the effect of tube tension reduction on image contrast and image quality in pediatric temporal bone computed tomography (CT). Methods: Seven lamb heads with infant-equivalent sizes were scanned repeatedly, using four tube tensions from 140 to 80kV while the CT-Dose Index (CTDI) was held constant. Scanning was repeated with four CTDI values from 30 to 3mGy. Image contrast was calculated for the middle ear as the Hounsfield unit (HU) difference between bone and air and for the inner ear as the HU difference between bone and fluid. The influence of tube tension on high-contrast detail delineation was evaluated using a phantom. The subjective image quality of eight middle and inner ear structures was assessed using a 4-point scale (scores 1-2â=âinsufficient; scores 3-4â=âsufficient). Results: Middle and inner ear contrast showed a near linear increase with tube tension reduction (râ=ââ0.94/â0.88) and was highest at 80kV. Tube tension had no influence on spatial resolution. Subjective image quality analysis showed significantly better scoring at lower tube tensions, with highest image quality at 80kV. However, image quality improvement was most relevant for low-dose scans. Conclusions: Image contrast in the temporal bone is significantly higher at low tube tensions, leading to a better subjective image quality. Highest contrast and best quality were found at 80kV. This image quality improvement might be utilized to further reduce the radiation dose in pediatric low-dose CT protocol
2-D materials for ultra-scaled field-effect transistors: hundred candidates under the ab initio microscope
Thanks to their unique properties single-layer 2-D materials appear as
excellent candidates to extend Moore's scaling law beyond the currently
manufactured silicon FinFETs. However, the known 2-D semiconducting components,
essentially transition metal dichalcogenides, are still far from delivering the
expected performance. Based on a recent theoretical study that predicts the
existence of more than 1,800 exfoliable 2-D materials, we investigate here the
100 most promising contenders for logic applications. Their "current vs.
voltage" characteristics are simulated from first-principles, combining
density-functional theory and advanced quantum transport calculations. Both n-
and p-type configurations are considered, with gate lengths ranging from 15
down to 5 nm. From this unprecedented collection of electronic materials, we
identify 13 compounds with electron and hole currents potentially much higher
than in future Si FinFETs. The resulting database widely expands the design
space of 2-D transistors and provides original guidelines to the materials and
device engineering community
Field-Effect Transistors based on 2-D Materials: a Modeling Perspective
Two-dimensional (2D) materials are particularly attractive to build the
channel of next-generation field-effect transistors (FETs) with gate lengths
below 10-15 nm. Because the 2D technology has not yet reached the same level of
maturity as its Silicon counterpart, device simulation can be of great help to
predict the ultimate performance of 2D FETs and provide experimentalists with
reliable design guidelines. In this paper, an ab initio modelling approach
dedicated to well-known and exotic 2D materials is presented and applied to the
simulation of various components, from thermionic to tunnelling transistors
based on mono- and multi-layer channels. Moreover, the physics of metal - 2D
semiconductor contacts is revealed and the importance of different scattering
sources on the mobility of selected 2D materials is discussed. It is expected
that modeling frameworks similar to the one described here will not only
accompany future developments of 2D devices, but will also enable them
DFTâGuided Discovery of EthynylâTriazolylâPhosphinates as Modular Electrophiles for Chemoselective Cysteine Bioconjugation and Profiling
We report the density functional theory (DFT) guided discovery of ethynylâtriazolylâphosphinates (ETPs) as a new class of electrophilic warheads for cysteine selective bioconjugation. By using CuIâcatalysed azide alkyne cycloaddition (CuAAC) in aqueous buffer, we were able to access a variety of functional electrophilic building blocks, including proteins, from diethynylâphosphinate. ETPâreagents were used to obtain fluorescent peptideâconjugates for receptor labelling on live cells and a stable and a biologically active antibodyâdrugâconjugate. Moreover, we were able to incorporate ETPâelectrophiles into an azideâcontaining ubiquitin under native conditions and demonstrate their potential in proteinâprotein conjugation. Finally, we showcase the excellent cysteineâselectivity of this new class of electrophile in mass spectrometry based, proteomeâwide cysteine profiling, underscoring the applicability in homogeneous bioconjugation strategies to connect two complex biomolecules.By means of density functional theory calculations, ethynylâtriazolylâphosphinates (ETPs) were discovered as modular and cysteineâselective electrophiles for bioconjugation. Using CuIâclick chemistry in aqueous buffers, this functional group can be easily introduced into azideâcontaining (bioâ)molecules. These reagents can be used for proteomeâwide cysteine profiling and to obtain functional peptideâ and protein conjugates, as well as proteinâprotein conjugates .
imageDeutsche Forschungsgemeinschaft
http://dx.doi.org/10.13039/501100001659Leibniz-Gemeinschaft
http://dx.doi.org/10.13039/501100001664Studienstiftung des Deutschen Volkes
http://dx.doi.org/10.13039/501100004350Alexander von Humboldt-Stiftung
http://dx.doi.org/10.13039/100005156Institute for Basic Science in KoreaPeer Reviewe
DFTâbasierte Entdeckung von EthynylâTriazolylâPhosphinaten als modulare Elektrophile fĂŒr die chemoselektive CysteinâBiokonjugation und Profilierung
Wir berichten ĂŒber eine Dichtefunktionaltheorie (DFT)-basierte Entdeckung von Ethinyl-Triazolyl-Phosphinaten (ETP) als eine neue Klasse elektrophiler Verbindungen fĂŒr die selektive Biokonjugation von Cystein. Mit Hilfe der CuI-katalysierten Azid-Alkin-Cycloaddition (CuAAC) in wĂ€ssrigem Puffer konnten wir eine Vielzahl funktioneller elektrophiler Bausteine, darunter auch Proteine, aus Diethynylphosphinat herstellen. Wir verwendeten diese ETP-Reagenzien, um fluoreszierende Peptid-Konjugate fĂŒr die Markierung von Rezeptoren auf lebenden Zellen sowie ein stabiles und biologisch aktives Antikörper-Wirkstoff-Konjugat zu erhalten. DarĂŒber hinaus konnten wir ETP-Elektrophile unter nativen Bedingungen in ein Azid-haltiges Ubiquitin einbauen und ihr Potenzial fĂŒr die Protein-Protein-Konjugation demonstrieren. SchlieĂlich zeigen wir die exzellente Cystein-SelektivitĂ€t dieser neuen Klasse von Elektrophilen in Massenspektrometrie basierten, proteomweiten ReaktivitĂ€tsstudien und unterstreichen damit die generelle Anwendbarkeit in homogenen Biokonjugationsstrategien zur VerknĂŒpfung zweier komplexer BiomolekĂŒle.Deutsche Forschungsgemeinschaft
http://dx.doi.org/10.13039/501100001659Leibniz-Gemeinschaft
http://dx.doi.org/10.13039/501100001664Studienstiftung des Deutschen Volkes
http://dx.doi.org/10.13039/501100004350Alexander von Humboldt-Stiftung
http://dx.doi.org/10.13039/100005156Institute for Basic Science in KoreaPeer Reviewe
A bone-thickness map as a guide for bone-anchored port implantation surgery in the temporal bone
The bone-anchored port (BAP) is an investigational implant, which is intended to be fixed on the temporal bone and provide vascular access. There are a number of implants taking advantage of the stability and available room in the temporal bone. These devices range from implantable hearing aids to percutaneous ports. During temporal bone surgery, injuring critical anatomical structures must be avoided. Several methods for computer-assisted temporal bone surgery are reported, which typically add an additional procedure for the patient. We propose a surgical guide in the form of a bone-thickness map displaying anatomical landmarks that can be used for planning of the surgery, and for the intra-operative decision of the implantâs location. The retro-auricular region of the temporal and parietal bone was marked on cone-beam computed tomography scans and tridimensional surfaces displaying the bone thickness were created from this space. We compared this method using a thickness map (n = 10) with conventional surgery without assistance (n = 5) in isolated human anatomical whole head specimens. The use of the thickness map reduced the rate of Dura Mater exposition from 100% to 20% and
OPEN ACCESS
Materials 2013, 6 5292
suppressed sigmoid sinus exposures. The study shows that a bone-thickness map can be
used as a low-complexity method to improve patientâs safety during BAP surgery in the
temporal bone
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