Nonlinear optics with full three-dimensional illumination

We investigate the nonlinear optical process of third-harmonic generation in the thus far unexplored regime of focusing the pump light from a full solid angle, where the nonlinear process is dominantly driven by a standing dipole-wave. We elucidate the influence of the focal volume and the pump intensity on the number of frequency-tripled photons by varying the solid angle from which the pump light is focused, finding good agreement between the experiments and numerical calculations. As a consequence of focusing the pump light to volumes much smaller than a wavelength cubed the Gouy phase does not limit the yield of frequency-converted photons. This is in stark contrast to the paraxial regime. We believe that our findings are generic to many other nonlinear optical processes when the pump light is focused from a full solid angle.Comment: 6 pages main text + 4 pages appendix, modified abstract and introduction + some other minor change

Unusual light spectra from a two-level atom in squeezed vacuum

We investigate the interaction of an atom with a multi-channel squeezed vacuum. It turns out that the light coming out in a particular channel can have anomalous spectral properties, among them asymmetry of the spectrum, absence of the central peak as well as central hole burning for particular parameters. As an example plane-wave squeezing is considered. In this case the above phenomena can occur for the light spectra in certain directions. In the total spectrum these phenomena are washed out.Comment: 16 pages, LaTeX, 3 figures (included via epsf

Wavelength-Scale Imaging of Trapped Ions using a Phase Fresnel lens

A microfabricated phase Fresnel lens was used to image ytterbium ions trapped in a radio frequency Paul trap. The ions were laser cooled close to the Doppler limit on the 369.5 nm transition, reducing the ion motion so that each ion formed a near point source. By detecting the ion fluorescence on the same transition, near diffraction limited imaging with spot sizes of below 440 nm (FWHM) was achieved. This is the first demonstration of imaging trapped ions with a resolution on the order of the transition wavelength.Comment: 8 pages, 3 figure

Influence of biological activity on 65Zn and 109Cd removal from tidal water by chronically-polluted mangrove sediments

The biological activity influence on the mangrove sediment capacity to remove 65Zn and 109Cd from tidal water was evaluated in a site chronically polluted. Benthic Activity Indexes (BAI), corresponding to relative estimates of biological impact on radiotracer accumulation, were higher for 109Cd (~ 38%) than for 65Zn (~ 10%) in the top centimetre of sediment. However, BAI exceeded 96% for deeper sediment layers. This apparent decrease in radiotracer diffusion into deep sediments through biological activity inhibition is stronger than reported for much less polluted mangrove nearby, suggesting that benthic organisms tolerant of chronic metal pollution may affect metal sorption mechanisms.info:eu-repo/semantics/publishedVersio

Stochastic wave function approach to the calculation of multitime correlation functions of open quantum systems

Within the framework of probability distributions on projective Hilbert space a scheme for the calculation of multitime correlation functions is developed. The starting point is the Markovian stochastic wave function description of an open quantum system coupled to an environment consisting of an ensemble of harmonic oscillators in arbitrary pure or mixed states. It is shown that matrix elements of reduced Heisenberg picture operators and general time-ordered correlation functions can be expressed by time-symmetric expectation values of extended operators in a doubled Hilbert space. This representation allows the construction of a stochastic process in the doubled Hilbert space which enables the determination of arbitrary matrix elements and correlation functions. The numerical efficiency of the resulting stochastic simulation algorithm is investigated and compared with an alternative Monte Carlo wave function method proposed first by Dalibard et al. [Phys. Rev. Lett. {\bf 68}, 580 (1992)]. By means of a standard example the suggested algorithm is shown to be more efficient numerically and to converge faster. Finally, some specific examples from quantum optics are presented in order to illustrate the proposed method, such as the coupling of a system to a vacuum, a squeezed vacuum within a finite solid angle, and a thermal mixture of coherent states.Comment: RevTex, 19 pages, 3 figures, uses multico

Generation of a wave packet tailored to efficient free space excitation of a single atom

We demonstrate the generation of an optical dipole wave suitable for the process of efficiently coupling single quanta of light and matter in free space. We employ a parabolic mirror for the conversion of a transverse beam mode to a focused dipole wave and show the required spatial and temporal shaping of the mode incident onto the mirror. The results include a proof of principle correction of the parabolic mirror's aberrations. For the application of exciting an atom with a single photon pulse we demonstrate the creation of a suitable temporal pulse envelope. We infer coupling strengths of 89% and success probabilities of up to 87% for the application of exciting a single atom for the current experimental parameters.Comment: to be published in Europ. Phys. J.

Differential influence of vemurafenib and dabrafenib on patients' lymphocytes despite similar clinical efficacy in melanoma

In this study, we demonstrate that vemurafenib but not dabrafenib reduces peripheral lymphocyte counts in melanoma patients while both agents show similar clinical efficacy. Within the lymphocyte compartment, vemurafenib selectively decreases circulating CD4+ T cells and changes their phenotype and function. This indicates that selective BRAFi need to be assessed individually for immunomodulatory effects, especially, when planning combinations with immunotherapie

A single amino acid distorts the Fc γ receptor IIIb/CD16b structure upon binding immunoglobulin G1 and reduces affinity relative to CD16a

Therapeutic mAbs engage Fc γ receptor III (CD16) to elicit a protective cell-mediated response and destroy the target tissue. Newer drugs designed to bind CD16a with increased affinity surprisingly also elicit protective CD16b-mediated responses. However, it is unclear why IgG binds CD16a with more than 10-fold higher affinity than CD16b even though these receptors share more than 97% identity. Here we identified one residue, Gly-129, that contributes to the greater IgG binding affinity of CD16a. The CD16b variant D129G bound IgG1 Fc with 2-fold higher affinity than CD16a and with 90-fold higher affinity than the WT. Conversely, the binding affinity of CD16a-G129D was decreased 128-fold relative to WT CD16a and comparably to that of WT CD16b. The interaction of IgG1 Fc with CD16a, but not with CD16b, is known to be sensitive to the composition of the asparagine-linked carbohydrates (N-glycans) attached to the receptor. CD16a and CD16b-D129G displaying minimally processed oligomannose N-glycans bound to IgG1 Fc with about 5.2-fold increased affinity compared with variants with highly processed complex-type N-glycans. CD16b and the CD16a-G129D variant exhibited a smaller 1.9-fold affinity increase with oligomannose N-glycans. A model of glycosylated CD16b bound to IgG1 Fc determined to 2.2 Å resolution combined with a 250-ns all-atom molecular dynamics simulation showed that the larger Asp-129 residue deformed the Fc-binding surface. These results reveal how Asp-129 in CD16b affects its binding affinity for IgG1 Fc and suggest that antibodies engineered to engage CD16b with high affinity must accommodate the Asp-129 side chain

Design of a mode converter for efficient light-atom coupling in free space

In this article, we describe how to develop a mode converter that transforms a plane electromagnetic wave into an inward moving dipole wave. The latter one is intended to bring a single atom or ion from its ground state to its excited state by absorption of a single photon wave packet with near-100% efficiency.Comment: RevTex4, 3 figures, revised version, accepted for publication at Appl. Phys.

Disruption of the sialic acid/Siglec-9 axis improves antibody-mediated neutrophil cytotoxicity towards tumor cells

Upregulation of surface expressed sialoglycans on tumor cells is one of the mechanisms which promote tumor growth and progression. Specifically, the interactions of sialic acids with sialic acid-binding immunoglobulin-like lectins (Siglecs) on lymphoid or myeloid cells transmit inhibitory signals and lead to suppression of anti-tumor responses. Here, we show that neutrophils express among others Siglec-9, and that EGFR and HER2 positive breast tumor cells express ligands for Siglec-9. Treatment of tumor cells with neuraminidases or a sialyl transferase inhibitor significantly reduced binding of a soluble recombinant Siglec-9-Fc fusion protein, while EGFR and HER2 expression remained unchanged. Importantly, the cytotoxic activity of neutrophils driven by therapeutic EGFR or HER2 antibodies in vitro was increased by blocking the sialic acid/Siglec interaction, either by reducing tumor cell sialylation or by a Siglec-9 blocking antibody containing an effector silenced Fc domain. In vivo a short-term xenograft mouse model confirmed the improved therapeutic efficacy of EGFR antibodies against sialic acid depleted, by a sialyltransferase inhibitor, tumor cells compared to untreated cells. Our studies demonstrate that sialic acid/Siglec interactions between tumor cells and myeloid cells can impair antibody dependent tumor cell killing, and that Siglec-9 on polymorphonuclear cells (PMN) is critically involved. Considering that PMN are often a highly abundant cell population in the tumor microenvironment, Siglec-9 constitutes a promising target for myeloid checkpoint blockade to improve antibody-based tumor immunotherapy