The silicon pixel tracking system for the ATLAS experiment at the Large Hadron Collider is described and the performance requirements are summarized. Detailed descriptions of the pixel detector electronics and the silicon sensors are given. The design, fabrication, assembly and performance of the pixel detector modules are presented. Data obtained from test beams as well as studies using cosmic rays are also discussed.

The ATLAS IBL CollaborationDuring the shutdown of the CERN Large Hadron Collider in 2013-2014, an additional pixel layer was installed between the existing Pixel detector of the ATLAS experiment and a new, smaller radius beam pipe. The motivation for this new pixel layer, the Insertable B-Layer (IBL), was to maintain or improve the robustness and performance of the ATLAS tracking system, given the higher instantaneous and integrated luminosities realised following the shutdown. Because of the extreme radiation and collision rate environment, several new radiation-tolerant sensor and electronic technologies were utilised for this layer. This paper reports on the IBL construction and integration prior to its operation in the ATLAS detector.The ATLAS [1] general purpose detector is used for the study of proton-proton (pp) and heavy-ion collisions at the CERN Large Hadron Collider (LHC) [2]. It successfully collected data at pp collision energies of 7 and 8 TeV in the period of 2010-2012, known as Run 1. Following an LHC shutdown in 2013-2014 (LS1), it has collected data since 2015 at a pp collision energy of 13 TeV (the so-called Run 2).The ATLAS inner tracking detector (ID) [1, 3] provides charged particle tracking with high efficiency in the pseudorapidity 1 range of |η| < 2.5. With increasing radial distance from the interaction region, it consists of silicon pixel and micro-strip detectors, followed by a transition radiation tracker (TRT) detector, all surrounded by a superconducting solenoid providing a 2 T magnetic field.The original ATLAS pixel detector [4,5], referred to in this paper as the Pixel detector, was the innermost part of the ID during Run 1. It consists of three barrel layers (named the B-Layer, Layer 1 and Layer 2 with increasing radius) and three disks on each side of the interaction region, to guarantee at least three space points over the full tracking |η| range. It was designed to operate for the Phase-I period of the LHC, that is with a peak luminosity of 1 × 10 34 cm −2 s −1 and an integrated luminosity of approximately 340 fb −1 corresponding to a TID of up to 50 MRad 2 and a fluence of up to 1 × 10 15 n eq /cm 2 NIEL. However, for luminosities exceeding 2 × 10 34 cm −2 s −1 , which are now expected during the Phase-I operation, the read-out efficiency of the Pixel layers will deteriorate. This paper describes the construction and surface integration of an additional pixel layer, the Insertable B-Layer (IBL) [6], installed during the LS1 shutdown between the B-Layer and a new smaller radius beam pipe. The main motivations of the IBL were to maintain the full ID tracking performance and robustness during Phase-I operation, despite read-out bandwidth limitations of the Pixel layers (in particular the B-Layer) at the expected Phase-I peak luminosity, and accumulated radiation damage to the silicon sensors and front-end electronics. The IBL is designed to operate until the end of Phase-I, when a full tracker upgrade is planned [7] for high luminosity LHC (HL-LHC) operation from approximately ...

Filamentous fungi represent an incredibly rich and rather overlooked reservoir of natural products, which often show potent bioactivity and find applications in different fields. Increasing the naturally low yields of bioactive metabolites within their host producers can be problematic, and yield improvement is further hampered by such fungi often being genetic intractable or having demanding culturing conditions. Additionally, total synthesis does not always represent a cost-effective approach for producing bioactive fungalinspired metabolites, especially when pursuing assembly of compounds with complex chemistry. This review aims at providing insights into heterologous production of secondary metabolites from filamentous fungi, which has been established as a potent system for the biosynthesis of bioactive compounds. Numerous advantages are associated with this technique, such as the availability of tools that allow enhanced production yields and directing biosynthesis towards analogues of the naturally occurring metabolite. Furthermore, a choice of hosts is available for heterologous expression, going from model unicellular organisms to well-characterised filamentous fungi, which has also been shown to allow the study of biosynthesis of complex secondary metabolites. Looking to the future, fungi are likely to continue to play a substantial role as sources of new pharmaceuticals and agrochemicals-either as producers of novel natural products or indeed as platforms to generate new compounds through synthetic biology.

Semi-synthetic derivatives of the tricyclic diterpene antibiotic pleuromutilin from the basidiomycete Clitopilus passeckerianus are important in combatting bacterial infections in human and veterinary medicine. These compounds belong to the only new class of antibiotics for human applications, with novel mode of action and lack of cross-resistance, representing a class with great potential. Basidiomycete fungi, being dikaryotic, are not generally amenable to strain improvement. We report identification of the seven-gene pleuromutilin gene cluster and verify that using various targeted approaches aimed at increasing antibiotic production in C. passeckerianus, no improvement in yield was achieved. The seven-gene pleuromutilin cluster was reconstructed within Aspergillus oryzae giving production of pleuromutilin in an ascomycete, with a significant increase (2106%) in production. This is the first gene cluster from a basidiomycete to be successfully expressed in an ascomycete, and paves the way for the exploitation of a metabolically rich but traditionally overlooked group of fungi.