168 research outputs found
Herstellung, Validierung und Anwendung von kombinatorischen Phagemid-Bibliotheken zur PrÀsentation langer Peptide
A phage display peptide library was created, which should possess the potential for formation of secondary structure in the library due to a length of 33 amino acids for the encoded peptides. This should allow for higher affinities to
many various types of target molecules than that which is achieved by using common libraries of shorter peptides.
The library was designed using the Cosmix-plexing method, which allows recombination of hyper-variable DNA regions. It uses type IIs restriction enzymes recognizing a defined DNA sequence, cutting in a fixed distance from that sequence. The
enzyme can bind outside of the hyper-variable region which encodes the library diversity. This method can be applied to increase the diversity of the primary library, or to allow the recombination of different coding DNA cassettes of peptides
from preselected populations which already showed affinity to a particular target, optimizing the binding capacities of these variants.
The library was created using synthetic DNA and, together with a modified expression vector, assessed for its constitution. Furthermore, the Cosmix-plexing recombination method was validated and established for this library.
Expression and presentation of the library peptides were validated, and the suitability of the library for screening was confirmed in affinity selection experiments.
In a screening of the library for ligands binding to CD28, specific peptide variants were enriched and recombined using Cosmix-plexing.
Indications of high affinity to CD28 (and of higher affinities for the recombined variants) could not be confirmed in BIAcore analysis.
The inability to obtain clear evidence of affinity of the synthetic peptides was assumed to be due to difficulties in the chemical synthesis of such peptides which contained some
very hydrophobic stretches. Some candidates have still not been successfully synthesized chemically.Es wurde eine Phage Display-Peptid-Bibliothek erstellt,
die durch eine Peptid-LÀnge von 33 AminosÀuren das Potential zur Ausbildung von SekundÀrstrukturen besitzen soll.
Diese Eigenschaft soll höhere AffinitĂ€ten zu einer Vielzahl verschiedener ZielmolekĂŒle zulassen, als es bisher mit kĂŒrzeren Peptiden aus gĂ€ngigen Peptid-Bibliotheken möglich ist.
Die Bibliothek wurde mit Hinsicht auf die Methode des Cosmix-plexing entwickelt, welche Rekombination in hypervariablen DNA-Regionen erlaubt. Sie verwendet Typ IIs-Restriktionsenzyme, die eine definierte DNA-Sequenz erkennen, aber in definiertem Abstand von dieser schneiden. So kann die Bindung eines Restriktionsenzyms auĂerhalb der hochvariablen Region stattfinden, innerhalb welcher die DiversitĂ€t der Bibliotheksstruktur kodiert ist. Mit dieser Technik kann man die
DiversitĂ€t der Ausgangsbibliothek steigern, oder die Rekombination verschiedener kodierender DNA-"Kassetten" von Peptiden aus vorselektierten Populationen vornehmen, die bereits eine AffinitĂ€t fĂŒr eine bestimmte ZieldomĂ€ne besitzen. So kann die AffinitĂ€t der Varianten optimiert werden.
Die aus synthetischer DNA erstellte Bibliothek wurde zusammen mit einem Expressionsvektor bzgl. ihrer Zusammensetzung untersucht und die Rekombinationsmethode des Cosmix-plexing validiert.
Expression und PrĂ€sentation der Peptide wurden validiert, und die Eignung der Bibliothek fĂŒr Screenings in AffinitĂ€tsanreicherungs-Versuchen bestĂ€tigt.
In einem Screening der Bibliothek auf Liganden fĂŒr CD28 wurden spezifische Peptide angereichert und mittels Cosmix-plexing rekombiniert.
Die Hinweise darauf, dass diese Peptide hohe AffinitÀten besitzen (und die rekombinierten Varianten höhere AffinitÀten), konnten in BIAcore-Analysen nicht bestÀtigt werden.
Die Schwierigkeiten beim Nachweis der AffinitĂ€t der synthetischen Peptide liegen vermutlich in Limitierungen bei der chemischen Synthese begrĂŒndet, da diese Peptide sehr hydrophobe Abschnitte aufweisen
Exact Results for the Bipartite Entanglement Entropy of the AKLT spin-1 chain
We study the entanglement between two domains of a spin-1 AKLT chain subject
to open boundary conditions. In this case the ground-state manifold is
four-fold degenerate. We summarize known results and present additional exact
analytical results for the von Neumann entanglement entropy, as a function of
both the size of the domains and the total system size for {\it all} four
degenerate ground-states. In the large limit the entanglement entropy
approaches and for the and states,
respectively. In all cases, it is found that this constant is approached
exponentially fast defining a length scale equal to the known
bulk correlation length.Comment: 11 pages, 3 figure
Isolating the Nonlinear Optical Response of a MoS Monolayer under Extreme Screening of a Metal Substrate
Transition metal dichalcogenides (TMDCs) monolayers, as two-dimensional (2D)
direct bandgap semiconductors, hold promise for advanced optoelectronic and
photocatalytic devices. Interaction with three-dimensional (3D) metals, like
Au, profoundly affects their optical properties, posing challenges in
characterizing the monolayer's optical responses within the semiconductor-metal
junction. In this study, using precise polarization-controlled final-state sum
frequency generation (FS-SFG), we successfully isolated the optical responses
of a MoS monolayer from a MoS/Au junction. The resulting SFG spectra
exhibit a linear lineshape, devoid of A or B exciton features, attributed to
the strong dielectric screening and substrate induced doping. The linear
lineshape illustrates the expected constant density of states (DOS) at the band
edge of the 2D semiconductor, a feature often obscured by excitonic
interactions in week-screening conditions such as in a free-standing monolayer.
Extrapolation yields the onset of a direct quasiparticle bandgap of about
eV, indicating a strong bandgap renormalization. This study not
only enriches our understanding of the optical responses of a 2D semiconductor
in extreme screening conditions but also provides a critical reference for
advancing 2D semiconductor-based photocatalytic applications.Comment: 14 pages, 4 figures + supplemental materia
Structural Insights into Hysteretic SpinâCrossover in a Set of Iron(II)â2,6âbis(1 H âPyrazolâ1âyl)Pyridine) Complexes
Bistable spin-crossover (SCO) complexes that undergo abrupt and hysteretic (ÎT) spin-state switching are desirable for molecule-based switching and memory applications. In this study, we report on structural facets governing hysteretic SCO in a set of iron(II)-2,6-bis(1H-pyrazol-1-yl)pyridine) (bpp) complexes â [Fe(bppâCOOEt)](X)â
CHNO (X=ClO, 1; X=BF, 2). Stable spin-state switching â T=288â
K; ÎT=62â
K â is observed for 1, whereas 2 undergoes above-room-temperature lattice-solvent content-dependent SCO â T=331â
K; ÎT=43â
K. Variable-temperature single-crystal X-ray diffraction studies of the complexes revealed pronounced molecular reorganizations â from the Jahn-Teller-distorted HS state to the less distorted LS state â and conformation switching of the ethyl group of the COOEt substituent upon SCO. Consequently, we propose that the large structural reorganizations rendered SCO hysteretic in 1 and 2. Such insights shedding light on the molecular origin of thermal hysteresis might enable the design of technologically relevant molecule-based switching and memory elements
Perforating freestanding molybdenum disulfide monolayers with highly charged ions
Porous single layer molybdenum disulfide (MoS) is a promising material
for applications such as DNA sequencing and water desalination. In this work,
we introduce irradiation with highly charged ions (HCIs) as a new technique to
fabricate well-defined pores in MoS. Surprisingly, we find a linear
increase of the pore creation efficiency over a broad range of potential
energies. Comparison to atomistic simulations reveals the critical role of
energy deposition from the ion to the material through electronic excitation in
the defect creation process, and suggests an enrichment in molybdenum in the
vicinity of the pore edges at least for ions with low potential energies.
Analysis of the irradiated samples with atomic resolution scanning transmission
electron microscopy reveals a clear dependence of the pore size on the
potential energy of the projectiles, establishing irradiation with highly
charged ions as an effective method to create pores with narrow size
distributions and radii between ca. 0.3 and 3 nm.Comment: 22 pages, 4 figure
Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data
We report a quasi-differential upper limit on the extremely-high-energy (EHE)
neutrino flux above GeV based on an analysis of nine years of
IceCube data. The astrophysical neutrino flux measured by IceCube extends to
PeV energies, and it is a background flux when searching for an independent
signal flux at higher energies, such as the cosmogenic neutrino signal. We have
developed a new method to place robust limits on the EHE neutrino flux in the
presence of an astrophysical background, whose spectrum has yet to be
understood with high precision at PeV energies. A distinct event with a
deposited energy above GeV was found in the new two-year sample, in
addition to the one event previously found in the seven-year EHE neutrino
search. These two events represent a neutrino flux that is incompatible with
predictions for a cosmogenic neutrino flux and are considered to be an
astrophysical background in the current study. The obtained limit is the most
stringent to date in the energy range between and GeV. This result constrains neutrino models predicting a three-flavor
neutrino flux of $E_\nu^2\phi_{\nu_e+\nu_\mu+\nu_\tau}\simeq2\times 10^{-8}\
{\rm GeV}/{\rm cm}^2\ \sec\ {\rm sr}10^9\ {\rm GeV}$. A significant part
of the parameter-space for EHE neutrino production scenarios assuming a
proton-dominated composition of ultra-high-energy cosmic rays is excluded.Comment: The version accepted for publication in Physical Review
Entanglement spectrum degeneracy and the Cardy formula in 1+1 dimensional conformal field theories
We investigate the effect of a global degeneracy in the distribution of the entanglement spectrum in conformal field theories in one spatial dimension. We relate the recently found universal expression for the entanglement Hamiltonian to the distribution of the entanglement spectrum. The main tool to establish this connection is the Cardy formula. It turns out that the Affleck-Ludwig non-integer degeneracy, appearing because of the boundary conditions induced at the entangling surface, can be directly read from the entanglement spectrum distribution. We also clarify the effect of the noninteger degeneracy on the spectrum of the partial transpose, which is the central object for quantifying the entanglement in mixed states. We show that the exact knowledge of the entanglement spectrum in some integrable spinchains provides strong analytical evidences corroborating our results
In-situ estimation of ice crystal properties at the South Pole using LED calibration data from the IceCube Neutrino Observatory
The IceCube Neutrino Observatory instruments about 1 km3 of deep, glacial ice at the geographic South Pole using 5160 photomultipliers to detect Cherenkov light emitted by charged relativistic particles. A unexpected light propagation effect observed by the experiment is an anisotropic attenuation, which is aligned with the local flow direction of the ice. Birefringent light propagation has been examined as a possible explanation for this effect. The predictions of a first-principles birefringence model developed for this purpose, in particular curved light trajectories resulting from asymmetric diffusion, provide a qualitatively good match to the main features of the data. This in turn allows us to deduce ice crystal properties. Since the wavelength of the detected light is short compared to the crystal size, these crystal properties do not only include the crystal orientation fabric, but also the average crystal size and shape, as a function of depth. By adding small empirical corrections to this first-principles model, a quantitatively accurate description of the optical properties of the IceCube glacial ice is obtained. In this paper, we present the experimental signature of ice optical anisotropy observed in IceCube LED calibration data, the theory and parametrization of the birefringence effect, the fitting procedures of these parameterizations to experimental data as well as the inferred crystal properties.</p
- âŠ