Computer-Aided Assembly Sequence Planning for High-Mix Low-Volume Products in the Electronic Appliances Industry

Electronic appliance manufacturers are facing the challenge of frequent product orders. Based on each product order, the assembly process and workstations need to be planned. An essential part of the assembly planning is defining the assembly sequence, considering the mechanical product’s design, and handling of the product’s components. The assembly sequence determines the order of processes for each workstation, the overall layout, and thereby time and cost. Currently, the assembly sequence is decided by industrial engineers through a manual approach that is time-consuming, complex, and requires technical expertise. To reduce the industrial engineers’ manual effort, a Computer-Aided Assembly Sequence Planning (CAASP) system is proposed in this paper. It compromises the components for a comprehensive system that aims to be applied practically. The system uses Computer-Aided Design (CAD) files to derive Liaison and Interference Matrices that represent a mathematical relationship between parts. Subsequently, an adapted Ant Colony Optimization Algorithm generates an optimized assembly sequence based on these relationships. Through a web browser-based application, the user can upload files and interact with the system. The system is conceptualized and validated using the CAD file of an electric motor example product. The results are discussed, and future work is outlined

A Swedish heterodyne facility instrument for the APEX telescope

In March 2008, the APEX facility instrument was installed on the telescope at the site of Lliano Chajnantor in northern Chile. The main objective of the paper is to introduce the new instrument to the radio astronomical community. It describes the hardware configuration and presents some initial results from the on-sky commissioning. The heterodyne instrument covers frequencies between 211 GHz and 1390 GHz divided into four bands. The first three bands are sideband-separating mixers operating in a single sideband mode and based on superconductor-insulator-superconductor (SIS) tunnel junctions. The fourth band is a hot-electron bolometer, waveguide balanced mixer. All bands are integrated in a closedcycle temperature-stabilized cryostat and are cooled to 4 K. We present results from noise temperature, sideband separation ratios, beam, and stability measurements performed on the telescope as a part of the receiver technical commissioning. Examples of broad extragalactic lines are also included

Selective Alpha-Particle Mediated Depletion of Tumor Vasculature with Vascular Normalization

BACKGROUND: Abnormal regulation of angiogenesis in tumors results in the formation of vessels that are necessary for tumor growth, but compromised in structure and function. Abnormal tumor vasculature impairs oxygen and drug delivery and results in radiotherapy and chemotherapy resistance, respectively. Alpha particles are extraordinarily potent, short-ranged radiations with geometry uniquely suitable for selectively killing neovasculature. METHODOLOGY AND PRINCIPAL FINDINGS: Actinium-225 ((225)Ac)-E4G10, an alpha-emitting antibody construct reactive with the unengaged form of vascular endothelial cadherin, is capable of potent, selective killing of tumor neovascular endothelium and late endothelial progenitors in bone-marrow and blood. No specific normal-tissue uptake of E4G10 was seen by imaging or post-mortem biodistribution studies in mice. In a mouse-model of prostatic carcinoma, (225)Ac-E4G10 treatment resulted in inhibition of tumor growth, lower serum prostate specific antigen level and markedly prolonged survival, which was further enhanced by subsequent administration of paclitaxel. Immunohistochemistry revealed lower vessel density and enhanced tumor cell apoptosis in (225)Ac-E4G10 treated tumors. Additionally, the residual tumor vasculature appeared normalized as evident by enhanced pericyte coverage following (225)Ac-E4G10 therapy. However, no toxicity was observed in vascularized normal organs following (225)Ac-E4G10 therapy. CONCLUSIONS: The data suggest that alpha-particle immunotherapy to neovasculature, alone or in combination with sequential chemotherapy, is an effective approach to cancer therapy

Extracellular matrix in the tumor microenvironment and its impact on cancer therapy

Solid tumors are complex organ-like structures that consist not only of tumor cells but also of vasculature, extracellular matrix (ECM), stromal, and immune cells. Often, this tumor microenvironment (TME) comprises the larger part of the overall tumor mass. Like the other components of the TME, the ECM in solid tumors differs significantly from that in normal organs. Intratumoral signaling, transport mechanisms, metabolisms, oxygenation, and immunogenicity are strongly affected if not controlled by the ECM. Exerting this regulatory control, the ECM does not only influence malignancy and growth of the tumor but also its response toward therapy. Understanding the particularities of the ECM in solid tumor is necessary to develop approaches to interfere with its negative effect. In this review, we will also highlight the current understanding of the physical, cellular, and molecular mechanisms by which the pathological tumor ECM affects the efficiency of radio-, chemo-, and immunotherapy. Finally, we will discuss the various strategies to target and modify the tumor ECM and how they could be utilized to improve response to therapy

Untersuchungen zur Erweiterung der Substratspezifität von Carboxylester-Hydrolasen

Carboxylester-Hydrolasen gehören zu den Enzymen, die durch hohe Lösungsmitteltolereanz, gute Lagerstabilität und ein breites Substratspektrum, am häufigsten in der Biokatalyse eingesetzt werden. Allerdings akzeptieren sie im Gegensatz zu Estern primärer und sekundärer Alkohole nur in Ausnahmefällen Ester tertiärer Alkohole als Substrate. In der Arbeit werden Wege untersucht mittels Gerichteter Evolution und rationalem Protein Design, Esterasevarianten zu generieren die in der Lage sind diese Substrate mit guten Enantioselektivitäten umzusetzen. Unter Verwendung von Methoden der Zufallsmutagenese werden große Enzymbibliotheken aufgebaut und mit einem mikrotiterplatten basierendem Assays-system auf neu generierte Aktivitäten untersucht. Mittels molecular modeling, werden Positionen vorhergesagt, an den gezielt Mutationen eingeführt werden können um eine erhöhte Enantioselektivität zu erreichen.Carboxylester hydrolases are among the enzymes used most frequently in biocatalysis. They show good solvent and storage stability and accept a broad range of substrates. While they hydrolyze esters of primary and secondary alcohols most of them are not able to convert esters of tertiary alcohols. In this thesis methods are examined to generate esterase variants by directed evolution and rational protein design which are able to hydrolyze those substrates with high enantioselectivity. Large enzyme libraries of random mutants are created and screened on new activities with a microtiterplate based assay system. Utilizing molecular modeling techniques positions were predicted to enhance enantioselectivity by directed mutagenesis

Activity of lipases and esterases towards tertiary alcohols : new insights into structure-function relationships

Hydrolytic enzymes are versatile biocatalysts and find increasing applications in organic synthesis and a considerable number of industrial processes using these enzymes have been commercialized. Within this class, lipases (E.C. 3.1.1.3) and carboxyl esterases (E.C. 3.1.1.1) are frequently used as they accept a broad range of non-natural substrates, are usually very stable in organic solvents and exhibit good to excellent stereoselectivity

Generation of complex human organoid models including vascular networks by incorporation of mesodermal progenitor cells

Organoids derived from human pluripotent stem cells are interesting models to study mechanisms of morphogenesis and promising platforms for disease modeling and drug screening. However, they mostly remain incomplete as they lack stroma, tissue resident immune cells and in particular vasculature, which create important niches during development and disease. We propose, that the directed incorporation of mesodermal progenitor cells (MPCs) into organoids will overcome the aforementioned limitations. In order to demonstrate the feasibility of the method, we generated complex human tumor as well as neural organoids. We show that the formed blood vessels display a hierarchic organization and mural cells are assembled into the vessel wall. Moreover, we demonstrate a typical blood vessel ultrastructure including endothelial cell-cell junctions, a basement membrane as well as luminal caveolae and microvesicles. We observe a high plasticity in the endothelial network, which expands, while the organoids grow and is responsive to anti-angiogenic compounds and pro-angiogenic conditions such as hypoxia. We show that vessels within tumor organoids connect to host vessels following transplantation. Remarkably, MPCs also deliver Iba1$^+$ cells that infiltrate the neural tissue in a microglia-like manner

Blockchain-driven supply chain finance: Towards a conceptual framework from a buyer perspective: Presentation held at 26th Annual IPSERA Conference 2017, 09-12 April 2017, Budapest

The main objective of this article is to develop a conceptual framework for blockchain-driven supply chain finance (SCF) solutions. The frame of reference intends to foster the coordination in buyer-supplier relations and eliminates existing inefficiencies in the execution of discrete SCF-instruments, such as reverse factoring and dynamic discounting. Moreover, we introduce value drivers for blockchain technology (BCT) to elaborate unique characteristics for its application in the field of SCF. While BCT is considered as one of the most disruptive enablers in financial technology (FinTech), it received only little attention within the emerging field of SCF. Therefore, the results contribute to future developments of appropriate SCF-solutions based on the newest technology innovations