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When it comes to the optimization of CAD models in the automation domain, neural networks currently play only a minor role. Optimizing abstract features such as automation capability is challenging, since they can be very difficult to simulate, are too complex for rule-based systems, and also have little to no data available for machine-learning methods. On the other hand, image manipulation methods that can manipulate abstract features in images such as StyleCLIP have seen much success. They rely on the latent space of pretrained generative adversarial networks, and could therefore also make use of the vast amount of unlabeled CAD data. In this paper, we show that such an approach is also suitable for optimizing abstract automation-related features of CAD parts. We achieved this by extending StyleCLIP to work with CAD models in the form of voxel models, which includes using a 3D StyleGAN and a custom classifier. Finally, we demonstrate the ability of our system for the optimiziation of automation-related features by optimizing the grabability of various CAD models. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Peer review under the responsibility of the scientific committee of the 33rd CIRP Design Conference.

Enzymes are highly specific biocatalysts, yet they can promote unwanted side reactions. Here we investigated the factors that direct catalysis in the enoyl-thioester reductase Etr1p. We show that a single conserved threonine is essential to suppress the formation of a side product that would otherwise act as a high-affinity inhibitor of the enzyme. Substitution of this threonine with isosteric valine increases side-product formation by more than six orders of magnitude, while decreasing turnover frequency by only one order of magnitude. Our results show that the promotion of wanted reactions and the suppression of unwanted side reactions operate independently at the active site of Etr1p, and that the active suppression of side reactions is highly conserved in the family of medium-chain dehydrogenases/reductases (MDRs). Our discovery emphasizes the fact that the active destabilization of competing transition states is an important factor during catalysis that has implications for the understanding and the de novo design of enzymes.

To determine whether the implementation of patient blood management (PBM) is effective to decrease the use of red blood cell without impairment of patient's safety.The World Health Organization encouraged all member states to implement PBM programs employing multiple combined strategies to increase and preserve autologous erythrocyte volume to minimize red blood cell transfusions. Data regarding safety issues are not sufficiently available.In this prospective, multicenter study, surgical inpatients from four German University Hospitals were analyzed before (pre-PBM) and after the implementation of PBM. PBM program included multiple measures (ie, preoperative optimization of hemoglobin levels, blood-sparing techniques, and standardization of transfusion practice). Primary aim was to show noninferiority of the PBM cohort with a margin of 0.5%. Secondary endpoints included red blood cell utilization.A total of 129,719 patients discharged between July 2012 and June 2015 with different inclusion periods for pre-PBM (54,513 patients) and PBM (75,206 patients) were analyzed. The primary endpoint was 6.53% in the pre-PBM versus 6.34% in the PBM cohort. The noninferiority aim was achieved (P0.001). Incidence of acute renal failure decreased in the PBM cohort (2.39% vs 1.67%; P0.001, regression model). The mean number of red blood cell transfused per patient was reduced from 1.21 ± 0.05 to 1.00 ± 0.05 (relative change by 17%, P0.001).The data presented show that implementation of PBM with a more conscious handling of transfusion practice can be achieved even in large hospitals without impairment of patient's safety. Further studies should elucidate which PBM measures are most clinically and cost effective.PBM-Study ClinicalTrials.gov, NCT01820949.

The enoyl-thioester reductase InhA catalyzes an essential step in fatty acid biosynthesis of Mycobacterium tuberculosis and is a key target of antituberculosis drugs to combat multidrug-resistant M. tuberculosis strains. This has prompted intense interest in the mechanism and intermediates of the InhA reaction. Here, using enzyme mutagenesis, NMR, stopped-flow spectroscopy, and LC–MS, we found that the NADH cofactor and the CoA thioester substrate form a covalent adduct during the InhA catalytic cycle. We used the isolated adduct as a molecular probe to directly access the second half-reaction of the catalytic cycle of InhA (i.e. the proton transfer), independently of the first half-reaction (i.e. the initial hydride transfer) and to assign functions to two conserved active-site residues, Tyr-158 and Thr-196. We found that Tyr-158 is required for the stereospecificity of protonation and that Thr-196 is partially involved in hydride transfer and protonation. The natural tendency of InhA to form a covalent C2-ene adduct calls for a careful reconsideration of the enzyme's reaction mechanism. It also provides the basis for the development of effective tools to study, manipulate, and inhibit the catalytic cycle of InhA and related enzymes of the short-chain dehydrogenase/reductase (SDR) superfamily. In summary, our work has uncovered the formation of a covalent adduct during the InhA catalytic cycle and identified critical residues required for catalysis, providing further insights into the InhA reaction mechanism important for the development of antituberculosis drugs.

Carbon dioxide (CO2) is a potent greenhouse gas whose presence in the atmosphere is a critical factor for global warming. At the same time atmospheric CO2 is also a cheap and readily available carbon source that can in principle be used to synthesize value-added products. However, as uncatalyzed chemical CO2-fixation reactions usually require quite harsh conditions to functionalize the CO2 molecule, not many processes have been developed that make use of CO2. In contrast to synthetical chemistry, Nature provides a multitude of different carboxylating enzymes whose carboxylating principle(s) might be exploited in biotechnology. This review focuses on the biochemical features of carboxylases, highlights possible evolutionary scenarios for the emergence of their reactivity, and discusses current, as well as potential future applications of carboxylases in organic synthesis, biotechnology and synthetic biology.

An improved understanding of enzymes' catalytic proficiency and stereoselectivity would further enable applications in chemistry, biocatalysis and industrial biotechnology. We use a chemical probe to dissect individual catalytic steps of enoyl-thioester reductases (Etrs), validating an active site tyrosine as the cryptic proton donor and explaining how it had eluded definitive identification. This information enabled the rational redesign of Etr, yielding mutants that create products with inverted stereochemistry at wild type-like turnover frequency.

An investment in a CIM technology, such as the introduction of an integrated design/SFM solution, requires a careful analysis of the advantages and disadvantages associated with the investment. Existing economic efficiency analysis approaches comprise not all angles of looking at the corporate data. The new approach presented in this article is characterized by the following points: strategic benefits are covered by a strategic outline concept, effects that can be quantified in monetary terms are not mixed up with those that cannot be monetarily represented, corporate data is broken down into individual levels of analysis and monetary quantities are taken into account in accordance with their time of occurrence. The whole approach is demonstrated using actual data of the SFM and jewellery industry.

A 71 year old Caucasian male, with a 50 pack year smoking history, presented with an enlarging tender chest wall swelling. It was originally thought to be a left axillary abscess and treated by incision and drainage. He was re-admitted a month later due …

Computer tomography (CT) is known to be as sensitive as magnetic resonance imaging (MRI) in detecting fungal microabscesses in chronic disseminated candidiasis. However, all imaging techniques have to be repeated in cases of suspected fungal infection. Therefore, use of the CT or MRI scan is limited. Only ultrasound (US) examinations can be repeated as often as needed. The disadvantage of US is a lack of sufficient documentation. We analyzed the value of computer-assisted documentation in serial ultrasonography of leukemia patients with suspected chronic disseminated candidiasis. From November 1996 until October 1997, a total of 220 ultrasound examinations (Kranzbuhler Logiq 500, 3.5 MHz convex array) were performed in 58 patients undergoing intensive chemotherapy. Initial US pictures were stored on a personal computer and compared with the live US at the time of reevaluation in cases of persistent fever. Ultrasound detected microabscesses in liver and/or spleen in eight of the 58 patients. Diagnosis was confirmed by autopsy/biopsy (n=6), blood culture (n=1), and a significant Candida antibody titer (n=1). Focal lesions occurred only after neutrophil recovery. However, a newly evolving nonhomogeneous, micronodular pattern of liver and spleen occurred during febrile neutropenia in three patients, and two of these developed focal lesions subsequently. Follow-up was easy, since US pictures could be compared directly with stored examinations on screen. We conclude that serial US is sensitive in detecting microabscesses in the liver or the spleen. Computer-assisted US documentation proved to be a helpful tool for detection as well as in the follow-up of patients with chronic disseminated candidiasis.

The pyridine nucleotides NADH and NADPH (NAD(P)H) are ubiquitous redox coenzymes that are present in all living cells. Although about 16% of all characterized enzymes use pyridine nucleotides as hydride donors or acceptors during catalysis, a detailed understanding of how the hydride is transferred between NAD(P)H and the corresponding substrate is lacking for many enzymes. Here we present evidence for a new mechanism that operates during enzymatic hydride transfers using crotonyl-CoA carboxylase/reductase (Ccr) as a case study. We observed a covalent ene intermediate between NADPH and the substrate, crotonyl-CoA, using NMR, high-resolution MS and stopped-flow spectroscopy. Preparation of the ene intermediate further allowed direct access to the catalytic cycle of other NADPH-dependent enzymes-including those from type II fatty acid biosynthesis-in an unprecedented way, suggesting that formation of NAD(P)H ene intermediates is a more general principle in catalysis.

Die methodische Planung betrieblicher Informationsverarbeitungsprozesse und die hiermit verbundene Komplexitat erfordert die Unterstutzung durch geeignete Planungsinstrumentarien. Derartige Instrumentarien sind im wesentlichen durch folgende Bestandteile gekennzeichnet: • ein Vorgehensmodell, das die zeitliche und logische Reihenfolge der Bearbeitungsschritte vorgibt und Anleitungen fur eine zielgerichtete Anwendung von Methoden zur Beschreibung betrieblicher Informationsverarbeitungsprozesse beinhaltet sowie • vorstrukturierte Referenzmodelle, die unter Abstraktion von unternehmensindividuellen Besonderheiten den Zugriff auf allgemeine Informationszusammenhange ermoglichen.

Die Ist-Analyse soll die notwendigen Basisinformationen zur Verfugung stellen, die den gegenwartigen Zustand des Industriezweigs moglichst objektiv reprasentieren. Ihr Zweck ist letztlich die Beschreibung der Unternehmen in ihrer Gesamtheit, deren Charakteristika sowie ihrer spezifischen Potentiale und Ressourcen.65)