Development of the nanobody display technology to target lentiviral vectors to antigen-presenting cells

Lentiviral vectors (LVs) provide unique opportunities for the development of immunotherapeutic strategies, as they transduce a variety of cells in situ, including antigen-presenting cells (APCs). Engineering LVs to specifically transduce APCs is required to promote their translation towards the clinic. We report on the Nanobody (Nb) display technology to target LVs to dendritic cells (DCs) and macrophages. This innovative approach exploits the budding mechanism of LVs to incorporate an APC-specific Nb and a binding-defective, fusion-competent form of VSV. G in the viral envelope. In addition to production of high titer LVs, we demonstrated selective, Nb-dependent transduction of mouse DCs and macrophages both in vitro and in situ. Moreover, this strategy was translated to a human model in which selective transduction of in vitro generated or lymph node (LN)-derived DCs and macrophages, was demonstrated. In conclusion, the Nb display technology is an attractive approach to generate LVs targeted to specific cell types

Assessing the Resolution of Methyltransferase-Mediated DNA Optical Mapping

[Image: see text] Interest in the human microbiome is growing and has been, for the past decade, leading to new insights into disease etiology and general human biology. Stimulated by these advances and in a parallel trend, new DNA sequencing platforms have been developed, radically expanding the possibilities in microbiome research. While DNA sequencing plays a pivotal role in this field, there are some technological hurdles that are yet to be overcome. Targeting of the 16S rRNA gene with amplicon sequencing, for instance, is frequently used for sample composition profiling due to its short sample-to-result time and low cost, which counterbalance its low resolution (genus to species level). On the other hand, more comprehensive methods, namely, whole-genome sequencing (WGS) and shallow shotgun sequencing, are capable of yielding single-gene- and functional-level resolution at a higher cost and much higher sample processing time. It goes without saying that the existing gap between these two types of approaches still calls for the development of a fast, robust, and low-cost analytical platform. In search of the latter, we investigated the taxonomic resolution of methyltransferase-mediated DNA optical mapping and found that strain-level identification can be achieved with both global and whole-genome analyses as well as using a unique identifier (UI) database. In addition, we demonstrated that UI selection in DNA optical mapping, unlike variable region selection in 16S amplicon sequencing, is not limited to any genomic location, explaining the increase in resolution. This latter aspect was highlighted by SCCmec typing in methicillin-resistant Staphylococcus aureus (MRSA) using a simulated data set. In conclusion, we propose DNA optical mapping as a method that has the potential to be highly complementary to current sequencing platforms

High-power single transverse and polarization mode VCSEL for silicon photonics integration

\ua9 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement. We demonstrate a 6.5 mW single transverse and polarization mode GaAs-based oxide-confined VCSEL at 850 nm. High power is enabled by a relatively large oxide aperture and an epitaxial design for low resistance, low optical loss, and high slope efficiency VCSELs. With the oxide aperture supporting multiple polarization unrestrained transverse modes, single transverse and polarization mode operation is achieved by a transverse and polarization mode filter etched into the surface of the VCSEL. While the VCSEL is specifically designed for light source integration on a silicon photonic integrated circuit, its performance in terms of power, spectral purity, polarization, and beam properties are of great interest for a large range of applications

Ternary q-Virasoro-Witt Hom-Nambu-Lie algebras

In this paper we construct ternary $q$-Virasoro-Witt algebras which $q$-deform the ternary Virasoro-Witt algebras constructed by Curtright, Fairlie and Zachos using $su(1,1)$ enveloping algebra techniques. The ternary Virasoro-Witt algebras constructed by Curtright, Fairlie and Zachos depend on a parameter and are not Nambu-Lie algebras for all but finitely many values of this parameter. For the parameter values for which the ternary Virasoro-Witt algebras are Nambu-Lie, the corresponding ternary $q$-Virasoro-Witt algebras constructed in this article are also Hom-Nambu-Lie because they are obtained from the ternary Nambu-Lie algebras using the composition method. For other parameter values this composition method does not yield Hom-Nambu Lie algebra structure for $q$-Virasoro-Witt algebras. We show however, using a different construction, that the ternary Virasoro-Witt algebras of Curtright, Fairlie and Zachos, as well as the general ternary $q$-Virasoro-Witt algebras we construct, carry a structure of ternary Hom-Nambu-Lie algebra for all values of the involved parameters

Analysis of defect-related optical degradation of VCSILs for photonic integrated circuits

Laser diodes are of paramount importance for on-chip telecommunications applications, and a wide range of sensing devices that require near-infrared sources. In this work, the devices under test are vertical-cavity silicon-integrated lasers (VCSILs) designed for operation at 845 nm in photonic integrated circuits (PICs). We focus on the analysis of the degradation of the optical performance during aging. To investigate the reliability of the devices, we carried out several stress tests at constant current, ranging from 3.5 mA to 4.5 mA representing a highly accelerated stress condition. We observed two different degradation modes. In the first part of the experiments, the samples exhibited a worsening of the threshold current, but the sub-threshold emission was unaffected by degradation. We associated this behavior to the diffusion of impurities that, from the p-contact, were crossing the upper mirror implying a worsening of the DBR optical absorption. In the second stage of the stress test, the devices showed a higher degradation rate of the threshold current, whose variation was found to be linearly correlated to the worsening of the sub-threshold emission. We related this second degradation mode to the migration of the same impurities degrading the top DBR that, when reaching the active region of the laser, induced an increase in the non-radiative recombination rate. In addition to that, we related the two degradation modes to the change in series resistance, which was ascribed to the resistivity increment of the top DBR first and of oxide aperture afterwards

Review on quality assurance along the CFRP value chain - Non-destructive testing of fabrics, preforms and CFRP by HF radio wave techniques

Eddy current testing is well established for non-destructive testing of electrical conductive materials [1]. The development of radio frequency (RF) eddy current technology with frequency ranges up to 100 MHz made it possible to extend the classical fields of application even towards less conductive materials like CFRP [2][3](Table 2). It turns out that RF eddy current technology on CFRP generates a growing number of valuable information for comprehensive material diagnostic. Both permittivity and conductivity of CFRP influence the complex impedance measured with RF eddy current devices. The electrical conductivity contains information about fiber texture like orientations, gaps or undulations in a multilayered material. The permittivity characterization influenced by dielectric properties allows the determination of local curing defects on CFRP e.g. hot spots, thermal impacts or polymer degradation. An explanation for that effect is seen in the measurement frequency range and the capacitive structure of the carbon rovings. Using radio wave frequencies for testing, the effect of displacement currents cannot be neglected anymore. The capacitive structures formed by the carbon rovings is supposed to further strengthen the dielectric influences on eddy current measurement signal [3]. This report gives an overview of several realized applications and should be understood as a general introduction of CFRP testing by HF Radio Wave techniques

Dendritic cells in cancer immunology and immunotherapy

Dendritic cells (DCs) are a diverse group of specialized antigen-presenting cells with key roles in the initiation and regulation of innate and adaptive immune responses. As such, there is currently much interest in modulating DC function to improve cancer immunotherapy. Many strategies have been developed to target DCs in cancer, such as the administration of antigens with immunomodulators that mobilize and activate endogenous DCs, as well as the generation of DC-based vaccines. A better understanding of the diversity and functions of DC subsets and of how these are shaped by the tumour microenvironment could lead to improved therapies for cancer. Here we will outline how different DC subsets influence immunity and tolerance in cancer settings and discuss the implications for both established cancer treatments and novel immunotherapy strategies.S.K.W. is supported by a European Molecular Biology Organization Long- Term Fellowship (grant ALTF 438– 2016) and a CNIC–International Postdoctoral Program Fellowship (grant 17230–2016). F.J.C. is the recipient of a PhD ‘La Caixa’ fellowship. Work in the D.S. laboratory is funded by the CNIC, by the European Research Council (ERC Consolidator Grant 2016 725091), by the European Commission (635122-PROCROP H2020), by the Ministerio de Ciencia, Innovación e Universidades (MCNU), Agencia Estatal de Investigación and Fondo Europeo de Desarrollo Regional (FEDER) (SAF2016-79040-R), by the Comunidad de Madrid (B2017/BMD-3733 Immunothercan- CM), by FIS- Instituto de Salud Carlos III, MCNU and FEDER (RD16/0015/0018-REEM), by Acteria Foundation, by Atresmedia (Constantes y Vitales prize) and by Fundació La Marató de TV3 (201723). The CNIC is supported by the Instituto de Salud Carlos III, the MCNU and the Pro CNIC Foundation, and is a Severo Ochoa Centre of Excellence (SEV-2015-0505).S