22 research outputs found

    Real-time determination of laser beam quality by modal decomposition

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    We present a real-time method to determine the beam propagation ratio M2 of laser beams. The all-optical measurement of modal amplitudes yields M2 parameters conform to the ISO standard method. The experimental technique is simple and fast, which allows to investigate laser beams under conditions inaccessible to other methods.Comment: 8 pages, 4 figures, published in Optics Expres

    AI/ML combined with next-generation sequencing of VHH immune repertoires enables the rapid identification of de novo humanized and sequence-optimized single domain antibodies: a prospective case study

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    Introduction: In this study, we demonstrate the feasibility of yeast surface display (YSD) and nextgeneration sequencing (NGS) in combination with artificial intelligence and machine learning methods (AI/ML) for the identification of de novo humanized single domain antibodies (sdAbs) with favorable early developability profiles.Methods: The display library was derived from a novel approach, in which VHH-based CDR3 regions obtained from a llama (Lama glama), immunized against NKp46, were grafted onto a humanized VHH backbone library that was diversified in CDR1 and CDR2. Following NGS analysis of sequence pools from two rounds of fluorescence-activated cell sorting we focused on four sequence clusters based on NGS frequency and enrichment analysis as well as in silico developability assessment. For each cluster, long short-term memory (LSTM) based deep generative models were trained and used for the in silico sampling of new sequences. Sequences were subjected to sequence- and structure-based in silico developability assessment to select a set of less than 10 sequences per cluster for production.Results: As demonstrated by binding kinetics and early developability assessment, this procedure represents a general strategy for the rapid and efficient design of potent and automatically humanized sdAb hits from screening selections with favorable early developability profiles

    Towards modular analysis of multi product lines

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    Software product-line engineering enables efficient develop-ment of tailor-made software by means of reusable artifacts. As practitioners increasingly develop software systems as product lines, there is a growing potential to reuse prod-uct lines in other product lines, which we refer to as multi product line. We identify challenges when developing multi product lines and propose interfaces for different levels of abstraction ranging from variability modeling to functional and non-functional properties. We argue that these inter-faces ease the reuse of product lines and identify research questions that need to be solved toward modular analysis of multi product lines

    Algemeine Geschichte der Länder und Völker von America : Mit vielen Kupfern

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    Nebst einer Vorrede Siegmund Jacob Baumgartens der h. Schrift Doctors und öffentl. Lehrers, auch des theologischen Seminarii Directors auf der königl. preußl. Friedrichsuniversität in HalleVerfasser gemäss GND; Initialen des Verfassers "J.F.S." am Ende der WidmungAus dem Vorbesitz der Naturforschenden Gesellschaft in Zürich; auf dem vorderen Vorsatzblatt des ersten Bandes Verbalexlibris, datiert auf 175

    Automated Analysis of Dependent Feature Models

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    Feature models specify valid combinations of features in software product lines. With dependent feature models (DFMs), we apply separation of concerns to feature models for two main benefits. First, we can modularize feature models into parts relevant to groups of stakeholders. Second, we are able to model dependencies between different software product lines in a multi-product-line scenario. To ensure consistency and correctness of DFMs, we have to apply analyses, such as dead-feature detection. We discuss why DFMs challenge the detection of inconsistencies, present how to reuse existing analyses for DFMs, and propose new analyses to supplement existing ones. We apply automated analyses in five steps and evaluate the approach using DFMs specified in VELVET by our prototype VeAnalyzer

    Data transmission with twisted light through a free-space to fiber optical communication link

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    Mode division multiplexing (MDM), where information is transmitted in the spatial modes of light, is mooted as a future technology with which to transmit large bits of information. However, one of the key issues in optical communication lies in connecting free-space to optical fiber networks, otherwise known as the 'last mile' problem. This is particularly problematic for MDM as the eigenmodes of free-space and fibers are in general not the same. Here we demonstrate a data transmission scheme across a free-space and fiber link using twisted light in the form of Laguerre–Gaussian (LG) azimuthal modes. As a proof-of-principle we design and implement a custom fiber where the supported LG modes can be grouped into five non-degenerate sets, and successfully transmit a gray-scale image across the composite link using one mode from each group, thereby ensuring minimal crosstalk

    A library approach for the de novo high-throughput isolation of humanized VHH domains with favorable developability properties following camelid immunization

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    ABSTRACTIn this study, we generated a novel library approach for high throughput de novo identification of humanized single-domain antibodies following camelid immunization. To achieve this, VHH-derived complementarity-determining regions-3 (CDR3s) obtained from an immunized llama (Lama glama) were grafted onto humanized VHH backbones comprising moderately sequence-diversified CDR1 and CDR2 regions similar to natural immunized and naïve antibody repertoires. Importantly, these CDRs were tailored toward favorable in silico developability properties, by considering human-likeness as well as excluding potential sequence liabilities and predicted immunogenic motifs. Target-specific humanized single-domain antibodies (sdAbs) were readily obtained by yeast surface display. We demonstrate that, by exploiting this approach, high affinity sdAbs with an optimized in silico developability profile can be generated. These sdAbs display favorable biophysical, biochemical, and functional attributes and do not require any further sequence optimization. This approach is generally applicable to any antigen upon camelid immunization and has the potential to significantly accelerate candidate selection and reduce risks and attrition rates in sdAb development

    Generation of Multiple Vector Optical Bottle Beams

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    We propose binary diffractive optical elements, combining several axicons of different types (axis-symmetrical and spiral), for the generation of a 3D intensity distribution in the form of multiple vector optical ‘bottle’ beams, which can be tailored by a change in the polarization state of the illumination radiation. The spatial dynamics of the obtained intensity distribution with different polarization states (circular and cylindrical of various orders) were investigated in paraxial mode numerically and experimentally. The designed binary axicons were manufactured using the e-beam lithography technique. The proposed combinations of optical elements can be used for the generation of vector optical traps in the field of laser trapping and manipulation, as well as for performing the spatial transformation of the polarization state of laser radiation, which is crucial in the field of laser-matter interaction for the generation of special morphologies of laser-induced periodic surface structures
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