Structural Basis of Fosmidomycin Action Revealed by the Complex with 2-C-Methyl-D-erythritol 4-phosphate Synthase (IspC): implications for the catalytic mechanism and anti-malaria drug development

2-C-Methyl-D-erythritol 4-phosphate synthase (IspC) is the first enzyme committed to isoprenoid biosynthesis in the methylerythritol phosphate pathway, which represents an alternative route to the classical mevalonate pathway. As it is present in many pathogens and plants, but not in man, this pathway has attracted considerable interest as a target for novel antibiotics and herbicides. Fosmidomycin represents a specific high-affinity inhibitor of IspC. Very recently, its anti-malaria activity in man has been demonstrated in clinical trials. Here, we present the crystal structure of Escherichia coli IspC in complex with manganese and fosmidomycin at 2.5 Å resolution. The (N-formyl-N-hydroxy)amino group provides two oxygen ligands to manganese that is present in a distorted octahedral coordination, whereas the phosphonate group is anchored in a specific pocket by numerous hydrogen bonds. Both sites are connected by a spacer of three methylene groups. The substrate molecule, 1-D-deoxyxylulose 5-phosphate, can be superimposed onto fosmidomycin, explaining the stereochemical course of the reaction

Precision farming – consideration of reduced exposure in the pollinator risk assessment

Observed declines in the distribution and abundance of various insect species have moved the topic of biodiversity and the protection of honey bees, an insect species of particular economic interest, into the focus of public attention. This also resulted in an increasing public pressure to reform the European agricultural policy and as part of this to minimise the amount of synthetic plant protection products used. In this context, so-called ‘precision farming’ offers a considerable potential for a reduced application of plant protection products by using precision application techniques that allow to adjust applications to the actual scale of target distribution within a field. Is however currently not possible to exactly quantify the subsequent decrease of exposure of non-target organisms. Focusing on honey bees, the authors are therefore in a first step proposing a field study design to quantify the direct and indirect exposure of honey bees and their colonies in relation to the ratio of treated to untreated field area and the application pattern used. Furthermore, parameters of the bee risk assessment scheme are discussed that could be suitable to describe exposure reduction by precision application.Observed declines in the distribution and abundance of various insect species have moved the topic of biodiversity and the protection of honey bees, an insect species of particular economic interest, into the focus of public attention. This also resulted in an increasing public pressure to reform the European agricultural policy and as part of this to minimise the amount of synthetic plant protection products used. In this context, so-called ‘precision farming’ offers a considerable potential for a reduced application of plant protection products by using precision application techniques that allow to adjust applications to the actual scale of target distribution within a field. Is however currently not possible to exactly quantify the subsequent decrease of exposure of non-target organisms. Focusing on honey bees, the authors are therefore in a first step proposing a field study design to quantify the direct and indirect exposure of honey bees and their colonies in relation to the ratio of treated to untreated field area and the application pattern used. Furthermore, parameters of the bee risk assessment scheme are discussed that could be suitable to describe exposure reduction by precision application

Contrastive Language-Image Pretrained (CLIP) Models are Powerful Out-of-Distribution Detectors

We present a comprehensive experimental study on pretrained feature extractors for visual out-of-distribution (OOD) detection. We examine several setups, based on the availability of labels or image captions and using different combinations of in- and out-distributions. Intriguingly, we find that (i) contrastive language-image pretrained models achieve state-of-the-art unsupervised out-of-distribution performance using nearest neighbors feature similarity as the OOD detection score, (ii) supervised state-of-the-art OOD detection performance can be obtained without in-distribution fine-tuning, (iii) even top-performing billion-scale vision transformers trained with natural language supervision fail at detecting adversarially manipulated OOD images. Finally, we argue whether new benchmarks for visual anomaly detection are needed based on our experiments. Using the largest publicly available vision transformer, we achieve state-of-the-art performance across all $18$ reported OOD benchmarks, including an AUROC of 87.6\% (9.2\% gain, unsupervised) and 97.4\% (1.2\% gain, supervised) for the challenging task of CIFAR100 $\rightarrow$ CIFAR10 OOD detection. The code will be open-sourced

Innovation Labs an Hochschulen in Deutschland. Relevante Erfolgsfaktoren für integrative und transformative Transferprozesse

Drängende gesellschaftliche Herausforderungen stellen etablierte Formen der Wissensproduktion und Wissensverbreitung in Frage und verlangen nach einer Erweiterung wissenschaftskultureller Normen und Praktiken. Diese wird unter anderem in einer stärkeren transdisziplinären Ausrichtung des Wissenschaftssystems gesehen, innerhalb dessen Innovation Labs als Plattformen und Gelegenheitsstrukturen für integrative und transformative Transferprozesse gegenwärtig einen Auftrieb erfahren. Jedoch ist noch wenig über inhaltliche und methodische Aspekte sowie institutionelle Bedingungen bekannt, die für den erfolgreichen Einsatz von Innovation Labs relevant sind. Basierend auf einer empirischen Falluntersuchung von neun Innovation Labs an Universitäten, Hochschulen für Angewandte Wissenschaften und Forschungseinrichtungen in Deutschland werden relevante Erfolgsfaktoren und Handlungsempfehlungen für die Integration von Wissenschaft und Gesellschaft abgeleitet. Innovation Labs werden anhand der inhaltlichen Kategorien Selbstverständnis, Akteur:innen, Methoden und Formate, Organisation und Evaluation sowie entlang der drei Ebenen Institution, Mensch und Umwelt betrachtet. Erfolgsfaktoren und Handlungsempfehlungen beziehen sich auf die fünf Kategorien und drei Ebenen

An Object-Based Approach to Implementing Distributed Concurrency Control

We have added distributed concurrency control to the MELD object system by representing in progress transactions as simulated objects. Transaction objects exploit MELD‘s normal message passing facilities to support the concurrency control mechanism. We have completed the implementation of an optimistic mechanism using transaction objects and have designed a two phase locking mechanism based on the same paradigm. We discuss the tradeoffs made and lessons learned, dealing both with transactions on objects and with transactions as objects

Fabry-Perot enhanced Faraday rotation in graphene

We demonstrate that giant Faraday rotation in graphene in the terahertz range due to the cyclotron resonance is further increased by constructive Fabry-Perot interference in the supporting substrate. Simultaneously, an enhanced total transmission is achieved, making this effect doubly advantageous for graphene-based magneto-optical applications. As an example, we present far-infrared spectra of epitaxial multilayer graphene grown on the C-face of 6H-SiC, where the interference fringes are spectrally resolved and a Faraday rotation up to 0.15 radians (9{\deg}) is attained. Further, we discuss and compare other ways to increase the Faraday rotation using the principle of an optical cavity

A5_7 Laser Pool

In this paper we ask the question of how feasible the concept of laser pool would be (using a laser instead of a pool cue). The laser is initially considered to be of comparable diameter to that of the ball, and is compared to a more focused beam. The geometry of the system is considered in detail, calculating how much photon momentum is transferred to the ball. We find the required laser power is approximately 3 × 1023W for the wide laser, and 5 × 1010W for the focused laser

A5_1 Exploration of Dune’s Ornithopters

The 2021 movie Dune utilises ornithopters with a unique eight winged design. In this paper we investigated the requirements needed for such a design to function. It was found that merely hovering would require the wings to beat ∼ 1.78 times a second, while requiring ∼ 183 horsepower each

A5_3 Sonic the Dead-Hog

Sonic is the protagonist of a video game series that goes by the same name. The games revolvearound sonic crossing obstacles at high speed. A signature of Sonic is that he rolls himself up into a ball and spins up to bolt off at the speed of sound. In this paper we will be looking at the heat Sonic produces from the friction of spinning up to this high speed and the conequences this has on him. Moreover, we will demonstrate that the generated energy per second of 89kJ leads to a temperature increase of 850°C per second in Sonic. Lastly, we will briefly cover why he cannot roll at a linear speed of the speed of sound due to limited frictional torque the ground can provide