Nonlinear optical response of photochromic azobenzene-functionalized self- assembled monolayers

The combination of photochromic and nonlinear optical (NLO) properties of azobenzene-functionalized self-assembled monolayers (SAMs) constitutes an intriguing step towards novel photonic and optoelectronic devices. By utilizing the second-order NLO process of second harmonic generation (SHG), supported by density-functional theory and correlated wave function method calculations, we demonstrate that the photochromic interface provides the necessary prerequisites en route towards possible future technical applications: we find a high NLO contrast on the order of 16% between the switching states. These are furthermore accessible reversibly and with high efficiencies in terms of cross sections on the order of 10−18 cm2 for both photoisomerization reactions, i.e., drivable by means of low-power LED light sources. Finally, both photostationary states (PSSs) are thermally stable at ambient conditions

High-Yield Production and Transfer of Graphene Flakes Obtained by Anodic Bonding

We report large-yield production of graphene flakes on glass by anodic bonding. Under optimum conditions, we counted several tens of flakes with lateral size around 20-30 {\mu}m and few tens of flakes with larger size. 60-70% of the flakes have negligible D peak. We show that it is possible to easily transfer the flakes by wedging technique. The transfer on silicon does not damage graphene and lowers the doping. The charge mobility of the transferred flakes on silicon is of the order of 6000 cm^2/V s (at carrier concentration of 10^12 cm^-2), which is typical for devices prepared on this substrate with exfoliated graphene.Comment: 17 pages, 6 figures; ACS Nano 201

Optical properties of azobenzene-functionalized self-assembled monolayers: Intermolecular coupling and many-body interactions

In a joint theoretical and experimental work, the optical properties of azobenzene-functionalized self-assembled monolayers (SAMs) are studied at different molecular packing densities. Our results, based on density- functional and many-body perturbation theory, as well as on differential reflectance (DR) spectroscopy, shed light on the microscopic mechanisms ruling photo-absorption in these systems. While the optical excitations are intrinsically excitonic in nature, regardless of the molecular concentration, in densely packed SAMs intermolecular coupling and local-field effects are responsible for a sizable weakening of the exciton binding strength. Through a detailed analysis of the character of the electron-hole pairs, we show that distinct excitations involved in the photo-isomerization at low molecular concentrations are dramatically broadened by intermolecular interactions. Spectral shifts in the calculated DR spectra are in good agreement with the experimental results. Our findings represent an important step forward to rationalize the excited-state properties of these complex materials

Targeting of human interleukin-12B by small hairpin RNAs in xenografted psoriatic skin

<p>Abstract</p> <p>Background</p> <p>Psoriasis is a chronic inflammatory skin disorder that shows as erythematous and scaly lesions. The pathogenesis of psoriasis is driven by a dysregulation of the immune system which leads to an altered cytokine production. Proinflammatory cytokines that are up-regulated in psoriasis include tumor necrosis factor alpha (TNFα), interleukin-12 (IL-12), and IL-23 for which monoclonal antibodies have already been approved for clinical use. We have previously documented the therapeutic applicability of targeting TNFα mRNA for RNA interference-mediated down-regulation by anti-TNFα small hairpin RNAs (shRNAs) delivered by lentiviral vectors to xenografted psoriatic skin. The present report aims at targeting mRNA encoding the shared p40 subunit (IL-12B) of IL-12 and IL-23 by cellular transduction with lentiviral vectors encoding anti-IL12B shRNAs.</p> <p>Methods</p> <p>Effective anti-IL12B shRNAs are identified among a panel of shRNAs by potency measurements in cultured cells. The efficiency and persistency of lentiviral gene delivery to xenografted human skin are investigated by bioluminescence analysis of skin treated with lentiviral vectors encoding the luciferase gene. shRNA-expressing lentiviral vectors are intradermally injected in xenografted psoriatic skin and the effects of the treatment evaluated by clinical psoriasis scoring, by measurements of epidermal thickness, and IL-12B mRNA levels.</p> <p>Results</p> <p>Potent and persistent transgene expression following a single intradermal injection of lentiviral vectors in xenografted human skin is reported. Stable IL-12B mRNA knockdown and reduced epidermal thickness are achieved three weeks after treatment of xenografted psoriatic skin with lentivirus-encoded anti-IL12B shRNAs. These findings mimick the results obtained with anti-TNFα shRNAs but, in contrast to anti-TNFα treatment, anti-IL12B shRNAs do not ameliorate the psoriatic phenotype as evaluated by semi-quantitative clinical scoring and by immunohistological examination.</p> <p>Conclusions</p> <p>Our studies consolidate the properties of lentiviral vectors as a tool for potent gene delivery and for evaluation of mRNA targets for anti-inflammatory therapy. However, in contrast to local anti-TNFα treatment, the therapeutic potential of targeting IL-12B at the RNA level in psoriasis is questioned.</p

Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants

Antibody-mediated immunotherapy is effective in humanized mice when combinations of broadly neutralizing antibodies (bNAbs) are used that target nonoverlapping sites on the human immunodeficiency virus type 1 (HIV-1) envelope. In contrast, single bNAbs can control simian–human immunodeficiency virus (SHIV) infection in immune-competent macaques, suggesting that the host immune response might also contribute to the control of viremia. Here, we investigate how the autologous antibody response in intact hosts can contribute to the success of immunotherapy. We find that frequently arising antibodies that normally fail to control HIV-1 infection can synergize with passively administered bNAbs by preventing the emergence of bNAb viral escape variants

A mammalian cell based FACS-panning platform for the selection of HIV-1 envelopes for vaccine development

An increasing number of broadly neutralizing monoclonal antibodies (bnMAb) against the HIV-1 envelope (Env) protein has been discovered recently. Despite this progress, vaccination efforts with the aim to re-elicit bnMAbs that provide protective immunity have failed so far. Herein, we describe the development of a mammalian cell based FACS-panning method in which bnMAbs are used as tools to select surface-exposed envelope variants according to their binding affinity. For that purpose, an HIV-1 derived lentiviral vector was developed to infect HEK293T cells at low multiplicity of infection (MOI) in order to link Env phenotype and genotype. For proof of principle, a gp145 Env model-library was established in which the complete V3 domain was substituted by five strain specific V3 loop sequences with known binding affinities to nMAb 447-52D, respectively. Env genes were recovered from selected cells by PCR, subcloned into a lentiviral vector (i) to determine and quantify the enrichment nMAb binders and (ii) to generate a new batch of transduction competent particles. After 2 selection cycles the Env variant with highest affinity was enriched 20-fold and represented 80% of the remaining Env population. Exploiting the recently described bnMAbs, this procedure might prove useful in selecting Env proteins from large Env libraries with the potential to elicit bnMAbs when used as vaccine candidates

Kinetik des Photoschaltens in selbstorganisierten Azobenzol-Alkanthiolen auf Gold(111)

In this work the photoisomerization of the azobenzene-alkanethiol Az11 in self-assembled monolayers (SAMs) is investigated. Azobenzene is a so-called molecular switch that changes its molecular structure reversibly between the stable trans and the metastable cis conformation. Besides the thermal cis–trans isomerization, conversion between these two states is possible by optical excitation with light of two different wavelengths: UV light and blue light predominantly trigger trans–cis and cis–trans isomerization, respectively. When anchoring molecular switches to a surface, its properties can be reversibly changed by external stimuli. However, the switches need to be electronically decoupled from the substrate. This can for example be achieved by self-assembly of azobenzene-alkanethiols. In the resulting SAMs significant lateral interactions occur. This is in contrast to azobenzene in solution, where intermolecular interactions can be neglected. From literature it is known that the photoisomerization in such densely-packed SAMs is hindered. By diluting the azobenzene moieties on the surface with alkanethiol “spacer” molecules a significant isomerization is observed. By X-ray photoelectron spectroscopy (XPS) it was verified that the concentration of impurities such as atomic sulfur or unbound thiols in the SAM is lower than approximately 3 %. Using near edge X-ray absorption fine structure spectroscopy (NEXAFS) we determined the average orientation of the azobenzene moieties: they are standing predominantly upright and are oriented more and more parallel to the surface if the density of azobenzenes in the SAM is decreased. By optical differential reflectance spectroscopy (DRS) we showed that strong excitonic coupling alters the absorption behavior of azobenzene: A blue-shifted excitonic band is formed. Its shift with respect to the monomer band is a function of the average distance between the azobenzene chromophores and their relative orientation. By examining the kinetics of the photoisomerization of a diluted Az11 SAM using NEXAFS we showed that upon illumination with UV light at least 50 % of the trans isomers are converted to cis, which is far better than in densely-packed SAMs. The efficiency of photoisomerization is in line with values reported for mixed azobenzene-alkanethiol/alkanethiol SAMs and still orders of magnitude better than for azobenzenes directly adsorbed on gold. By examining the kinetics of the photoisomerization with DRS we could show that the blue-shifted excitonic band, despite its significant intensity, does not contribute to the isomerization process. Instead, the isomerization is driven by chromophores that are not part of the aggregate, e.g., regions of disorder in between different domains of molecular arrangements.In dieser Arbeit wurde die Photoisomerisierung des Azobenzolalkanthiols Az11 in selbstorganisierten Monolagen (SAMs) untersucht. Azobenzol ist ein sogenannter molekularer Schalter, der seine Molekülstruktur reversibel zwischen der trans-Grundzustandskonfiguration und der metastabilen cis-Konfiguration ändert. Neben der thermischen Relaxation von cis nach trans kann die Isomerisierung auch durch Licht ausgelöst werden: Mit UV-Licht bzw. blauem Licht wird jeweils überwiegend die trans–cis bzw. die cis–trans-Isomerisierung angeregt. Durch Verankerung solcher molekularer Schalter auf einer Oberfläche können dessen Eigenschaften durch äußere Stimuli reproduzierbar geändert werden. Allerdings müssen die Schaltermoleküle dafür elektronisch vom Substrat entkoppelt sein. Dies kann beispielsweise in SAMs aus Azobenzolalkanthiolen erreicht werden. Allerdings treten in solchen Monolagen, im Gegensatz zu in Lösung befindlichem Azobenzol, signifikante intermolekulare Wechselwirkungen auf. Diese behindern dann die Photoisomerisierung. Bei durch „Abstandshaltermoleküle“ verringerter Dichte der Azobenzole ist aber auch im SAM signifikante Photoisomerisierung zu beobachten. Mittels Röntgenphotoelektronenspektroskopie (XPS) haben wir gezeigt, dass in den von uns präparierten SAMs die Konzentration von Verunreinigungen wie etwa atomarem oder ungebundenem Schwefel kleiner als etwa 3 % ist. Die mittlere Orientierung der Azobenzole haben wir mittels Röntgen-Nahkanten-Absorptions-Spektroskopie (NEXAFS) bestimmt: die Azobenzole stehen überwiegend aufrecht und sind bei abnehmender Azobenzoldichte zunehmend flacher orientiert. Die intermolekularen Wechselwirkungen wurden mittels optischer Differenzreflektionsspektroskopie (DRS) untersucht: Es wird ein Exzitonenband, das bezüglich der Absorptionsbande des Einzelmoleküls zu kürzeren Wellenlängen verschoben ist, beobachtet. Die spektrale Verschiebung ist abhängig vom mittleren Abstand der Azobenzol-Chromophore und ihrer Orientierung zueinander. Wir haben die Photoisomerisierungskinetik von SAMs mit reduzierter Chromophordichte mittels NEXAFS und DRS untersucht. Unter UV-Licht werden mindestens 50 % der trans-Isomere zu cis umgesetzt, signifikant mehr als in dichtgepackten SAMs. Die Effizienz des Schaltprozesses ist vergleichbar mit der von verwandten Systemen und um Größenordnungen besser als bei direkt auf der Oberfläche adsorbiertem Azobenzol. Das blauverschobene Exzitonenband trägt trotz seiner hohen Intensität nicht zum Isomerisierungsprozess bei. Stattdessen wird die Isomerisierung durch Anregung von trans-Isomeren, die sich an Domänengrenzen oder anderen Fehlstellen befinden, getrieben