New progresses in the IFMIF target and test cell design and a proposal for the specimen flow

The development of the conceptual design of the IFMIF target and test cell (TTC) is briefly summarized by outlining the previous reference TTC design and the current modular test cell (MTC) concept. Based on the MTC concept, the latest progresses of the preliminary engineering design of the key TTC components, including the TTC vessel, the top shielding plugs, the removable intermediate ring, and the test module interface heads, are described. A specimen flow, based on handling requirements of the high flux test module, between the TTC, access cell (AC), test module handling cell (TMHC) and the post irradiation examination facilities is proposed as well as the function of the AC and TMHC is preliminary defined. The TMHC is proposed to be divided into a component handling cell and a rig handling cell regarding the dimension differences of the components to be handled inside of the cells. Re-use of irradiated specimens for another campaign of irradiation is also considered in this specimen flow.     

Polymers interfacing with biology

The development of various controlled radical polymerization techniques as well as site- and residue specific strategies to modify peptides/proteins with synthetic polymers have made polymer chemistry a powerful tool to address materials problems at the biology interface. This article will present recent examples for bioactive surface modification and polymer therapeutics; it will highlight the use of controlled radical polymerization techniques and bioconjugation strategies to develop surface coatings for regenerative medicine and diagnostics, respectively, polymer-based nanomedicines.     

Preparation and antitumour properties of the enantiomers of a hypoxia-selective nitro analogue of the duocarmycins

Racemic 2-{[1-(chloromethyl)-5-nitro-3-{5-[2-(dimethylamino)ethoxy]indol-2-carbonyl}-1,2-dihydro-3H-benzo[e]indol-7-yl]sulfonyl}aminoethyl dihydrogen phosphate, a synthetic nitro derivative of the duocarmycins, is a hypoxia-selective prodrug active against radiation-resistant tumour cells at nontoxic doses in mice. An intermediate in the synthesis of this prodrug was resolved by chiral HPLC and the absolute configuration assigned by X-ray crystallography. The intermediate was used to prepare the prodrug's enantiomers, and also the enantiomers of the active nitro and amino metabolites. In vitro analysis in the human cervical carcinoma cell line SiHa showed that both nitro enantiomers are hypoxia-selective cytotoxins, but the "natural" S enantiomer is at least 20-fold more potent. Examination of extracellular amino metabolite concentrations demonstrated no enantioselectivity in the hypoxia-selective reduction of nitro to amino. Low levels of amino derivative were also found in aerobic cell suspensions, sufficient to account for the observed oxic toxicity of the nitro form. At an equimolar dose in SiHa-tumour bearing animals, the (-)-R enantiomer of the prodrug was inactive, while the (+)-S enantiomer caused significantly more hypoxic tumour cell kill than the racemate. At this dose, the combination of (+)-S-prodrug and radiation eliminated detectable colony-forming cells in four out of five treated tumour-bearing animals.     

Generation of native polythiophene/PCBM composite nanoparticles via the combination of ultrasonic micronization of droplets and thermocleaving from aqueous dispersion

We report the preparation of native polythiophene (n-PT)/[6, 6]-phenyl-C61-butyric acid methyl ester (PCBM) composite nanoparticles from a poly[3-(2-methylhex-2-yl)oxy-carbonyldithiophene] (P3MHOCT)/PCBM aqueous dispersion prepared from an ultrasonically generated emulsion. The subsequent steps involve both ultrasonic generation of microdroplets in argon as a carrier gas and drying followed by thermocleaving of the P3MHOCT component in the gas phase. The chemical transition from P3MHOCT to n-PT was confirmed by Fourier transform infrared (FTIR) spectroscopy. The morphology and size of n-PT/PCBM nanoparticles were determined by atomic force microscopy (AFM), small-angle x-ray scattering (SAXS) and grazing incidence SAXS (GISAXS), giving an average size of ～ 140?nm. The GISAXS results reveal that n-PT/PCBM nanoparticles pack in an ordered structure as opposed to the P3MHOCT/PCBM nanoparticles. The successful vapour-phase preparation of phase-separated n-PT/PCBM nanoparticles provides a new route to all-aqueous processing of conjugated materials relevant to efficient polymer solar cells with long operational stability. The use of ultrasound was involved in both liquid and gas phases demonstrating it as a low-cost processing method.     

Muscular and Molecular Pathology Associated with SPATA5 Deficiency in a Child with EHLMRS

Mutations in the SPATA5 gene are associated with epilepsy, hearing loss and mental retardation syndrome (EHLMRS). While SPATA5 is ubiquitously expressed and is attributed a role within mitochondrial morphogenesis during spermatogenesis, there is only limited knowledge about the associated muscular and molecular pathology. This study reports on a comprehensive workup of muscular pathology, including proteomic profiling and microscopic studies, performed on an 8-year-old girl with typical clinical presentation of EHLMRS, where exome analysis revealed two clinically relevant, compound-heterozygous variants in SPATA5. Proteomic profiling of a quadriceps biopsy showed the dysregulation of 82 proteins, out of which 15 were localized in the mitochondrion, while 19 were associated with diseases presenting with phenotypical overlap to EHLMRS. Histological staining of our patient’s muscle biopsy hints towards mitochondrial pathology, while the identification of dysregulated proteins attested to the vulnerability of the cell beyond the mitochondria. Through our study we provide insights into the molecular etiology of EHLMRS and provide further evidence for a muscle pathology associated with SPATA5 deficiency, including a pathological histochemical pattern accompanied by dysregulated protein expression.     

Risk of cross-infection in a hospital ward with downward ventilation

A two-bed hospital ward with one standing healthcare person and a ceiling-mounted lowimpulse semicircular inlet diffuser is simulated in a full-scale room. Tracer gas is used for simulating gaseous contaminants, and the concentration is measured at different air change rates and different postures of the patients. A textile partition between the beds, which is typical in a hospital ward, is used for protection of the patients in some of the experiments. Three different layouts of return openings are tested. One layout with one opening at the ceiling, another with four openings at the wall opposite to the inlet diffuser, and one with a high location of these four openings. The downward recirculating flow is on average parallel with the partition, and in most cases the partition does not decrease cross-infection. A high location of the four return openings decreases the risk of cross-infection.     

TUM autonomous motorsport: An autonomous racing software for the Indy Autonomous Challenge

For decades, motorsport has been an incubator for innovations in the automotive sector and brought forth systems, like, disk brakes or rearview mirrors. Autonomous racing series such as Roborace, F1Tenth, or the Indy Autonomous Challenge (IAC) are envisioned as playing a similar role within the autonomous vehicle sector, serving as a proving ground for new technology at the limits of the autonomous systems capabilities. This paper outlines the software stack and approach of the TUM Autonomous Motorsport team for their participation in the IAC, which holds two competitions: A single-vehicle competition on the Indianapolis Motor Speedway and a passing competition at the Las Vegas Motor Speedway. Nine university teams used an identical vehicle platform: A modified Indy Lights chassis equipped with sensors, a computing platform, and actuators. All the teams developed different algorithms for object detection, localization, planning, prediction, and control of the race cars. The team from Technical University of Munich (TUM) placed first in Indianapolis and secured second place in Las Vegas. During the final of the passing competition, the TUM team reached speeds and accelerations close to the limit of the vehicle, peaking at around $270\text{km h}{}^{-1}$ and $28ms{}^{-2}$. This paper will present details of the vehicle hardware platform, the developed algorithms, and the workflow to test and enhance the software applied during the 2-year project. We derive deep insights into the autonomous vehicle's behavior at high speed and high acceleration by providing a detailed competition analysis. On the basis of this, we deduce a list of lessons learned and provide insights on promising areas of future work based on the real-world evaluation of the displayed concepts.