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- Akiba, K., et al.
(author)
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The LHCb VELO Upgrade module construction
- 2024
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In: Journal of Instrumentation. - : Institute of Physics Publishing (IOPP). - 1748-0221. ; 19:6
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Journal article (peer-reviewed)abstract
- The LHCb detector has undergone a major upgrade for LHC Run 3. This Upgrade I detector facilitates operation at higher luminosity and utilises full-detector information at the LHC collision rate, critically including the use of vertex information. A new vertex locator system, the VELO Upgrade, has been constructed. The core element of the new VELO are the double-sided pixelated hybrid silicon detector modules which operate in vacuum close to the LHC beam in a high radiation environment. The construction and quality assurance tests of these modules are described in this paper. The modules incorporate 200 mu m thick, n -on -p silicon sensors bump-bonded to 130 nm technology ASICs. These are attached with high precision to a silicon microchannel substrate that uses evaporative CO 2 cooling. The ASICs are controlled and read out with flexible printed circuits that are glued to the substrate and wire -bonded to the chips. The mechanical support of the module is given by a carbon fibre plate, two carbon fibre rods and an aluminium plate. The sensor attachment was achieved with an average precision of 21 mu m, more than 99.5% of all pixels are fully functional, and a thermal figure of merit of 3 Kcm 2 W - 1 was achieved. The production of the modules was successfully completed in 2021, with the final assembly and installation completed in time for data taking in 2022.
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| 2. |
- Campbell, Brittany B., et al.
(author)
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Comprehensive Analysis of Hypermutation in Human Cancer
- 2017
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In: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 171:5
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Journal article (peer-reviewed)abstract
- © 2017 Elsevier Inc. We present an extensive assessment of mutation burden through sequencing analysis of > 81,000 tumors from pediatric and adult patients, including tumors with hypermutation caused by chemotherapy, carcinogens, or germline alterations. Hypermutation was detected in tumor types not previously associated with high mutation burden. Replication repair deficiency was a major contributing factor. We uncovered new driver mutations in the replication-repair-associated DNA polymerases and a distinct impact of microsatellite instability and replication repair deficiency on the scale of mutation load. Unbiased clustering, based on mutational context, revealed clinically relevant subgroups regardless of the tumors' tissue of origin, highlighting similarities in evolutionary dynamics leading to hypermutation. Mutagens, such as UV light, were implicated in unexpected cancers, including sarcomas and lung tumors. The order of mutational signatures identified previous treatment and germline replication repair deficiency, which improved management of patients and families. These data will inform tumor classification, genetic testing, and clinical trial design. A large-scale analysis of hypermutation in human cancers provides insights into tumor evolution dynamics and identifies clinically actionable mutation signatures.
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- Durcik, Martina, et al.
(author)
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New Dual Inhibitors of Bacterial Topoisomerases with Broad-Spectrum Antibacterial Activity and In Vivo Efficacy against Vancomycin-Intermediate Staphylococcus aureus
- 2023
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 66:6, s. 3968-3994
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Journal article (peer-reviewed)abstract
- A new series of dual low nanomolar benzothiazole inhibitors of bacterial DNA gyrase and topoisomerase IV were developed. The resulting compounds show excellent broad-spectrum antibacterial activities against Gram-positive Enterococcus faecalis, Enterococcus faecium and multidrug resistant (MDR) Staphylococcus aureus strains [best compound minimal inhibitory concentrations (MICs): range, <0.03125–0.25 μg/mL] and against the Gram-negatives Acinetobacter baumannii and Klebsiella pneumoniae (best compound MICs: range, 1–4 μg/mL). Lead compound 7a was identified with favorable solubility and plasma protein binding, good metabolic stability, selectivity for bacterial topoisomerases, and no toxicity issues. The crystal structure of 7a in complex with Pseudomonas aeruginosa GyrB24 revealed its binding mode at the ATP-binding site. Expanded profiling of 7a and 7h showed potent antibacterial activity against over 100 MDR and non-MDR strains of A. baumannii and several other Gram-positive and Gram-negative strains. Ultimately, in vivo efficacy of 7a in a mouse model of vancomycin-intermediate S. aureus thigh infection was also demonstrated.
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| 9. |
- Granlund, A, et al.
(author)
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Ultrasound-guided percutaneous cholecystostomy in high-risk surgical patients.
- 2001
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In: Langenbeck's archives of surgery (Print). - 1435-2443 .- 1435-2451. ; 386:3, s. 212-7
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: In critically ill patients, cholecystectomy is associated with a high mortality rate. The aim of this study was to evaluate the safety, efficacy and long-term outcome of ultrasound-guided percutaneous cholecystostomy (USGPC) in critically ill patients with acute cholecystitis.MATERIALS AND METHODS: Clinical records of 51 patients, all considered high-risk surgical patients, with acute cholecystitis treated with USGPC between 1987 and 1999, were retrospectively reviewed. Response was defined as improvement in clinical symptoms and signs, and/or reduction in c-reactive protein and white blood count levels within 72 h. Long-term results were evaluated by means of clinical records and written correspondence.RESULTS: Gallbladder stones were seen in 28 patients whereas 23 had acalculous cholecystitis. Ninety percent showed clinical improvement after USGPC. Cholecystectomy was performed in 16%, of which 6% after recurrent cholecystitis. Recurrence of cholecystitis occurred in 22%. Hospital mortality was 16%. None of the deaths was procedure related or related to acute cholecystitis alone. Major complications relating to the USGPC were rare (4%), while minor catheter-related complications were quite common.CONCLUSIONS: USGPC is a procedure with few complications and a high success rate. In patients with acalculous cholecystitis as well as in many patients with calculous cholecystitis, no further treatment was needed.
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