A holistic DC link architecture design method for multiphase Integrated Modular Motor Drives

This article describes a holistic DC link architecture design method that considers the end-application of the drive and its corresponding constraints e.g. the maximum battery ripple current for a battery-supplied inverter. Also, the levers that are available to comply with the design criteria are presented e.g. the use of interleaved carrier waves. This holistic approach will result in a feasible and performant Integrated Modular Motor Drive from an application point of view. Finally, a platform is presented that was developed for feasibility and performance assessment of various DC link architectures obtained from the holistic design approach. The platform comprises a fifteen phase integrable modular motor drive for an Axial Flux Permanent Magnet Synchronous Machine. It allows non-intrusive reconfiguration of the DC link architecture and implementation of various control strategies and interleaved PWM schemes

Simultaneous DC-link and stator current ripple reduction with interleaved carriers in multiphase controlled integrated modular motor drives

To meet the demand for increasingly high power density in electric drives, the concept of a so-called integrated modular motor drive has emerged. The machine is composed of multiple identical modules, which receive individual control signals for multiphase control, to reduce unwanted stator current harmonics. Each module is equipped with its own power electronic converter, which is integrated in the machine housing. This integration imposes strict constraints on the DC-link capacitor design. To reduce the DC-link current ripple, and hence relax the design constraints on the DC-link capacitor, without compromising the possibility to eliminate unwanted stator current harmonics by means of multiphase control, a new interleaving strategy is proposed in this paper. The n modules of the machine are split into p subgroups of m modules for interleaving, while the n-phase control is preserved. An analytical model, simulations and experimental results are provided for a 4 kW test setup, confirming that multiphase control can be combined with interleaving. As a result, both the stator current harmonic distortion and the DC-link current ripple can be reduced simultaneously

Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration

Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In the present study, we analyzed the SQSTM1 coding sequence for mutations in an extended cohort of 1,808 patients with frontotemporal lobar degeneration (FTLD), ascertained within the European Early-Onset Dementia consortium. As control dataset, we sequenced 1,625 European control individuals and analyzed whole-exome sequence data of 2,274 German individuals (total n = 3,899). Association of rare SQSTM1 mutations was calculated in a meta-analysis of 4,332 FTLD and 10,240 control alleles. We identified 25 coding variants in FTLD patients of which 10 have not been described. Fifteen mutations were absent in the control individuals (carrier frequency < 0.00026) whilst the others were rare in both patients and control individuals. When pooling all variants with a minor allele frequency < 0.01, an overall frequency of 3.2 % was calculated in patients. Rare variant association analysis between patients and controls showed no difference over the whole protein, but suggested that rare mutations clustering in the UBA domain of SQSTM1 may influence disease susceptibility by doubling the risk for FTLD (RR = 2.18 [95 % CI 1.24-3.85]; corrected p value = 0.042). Detailed histopathology demonstrated that mutations in SQSTM1 associate with widespread neuronal and glial phospho-TDP-43 pathology. With this study, we provide further evidence for a putative role of rare mutations in SQSTM1 in the genetic etiology of FTLD and showed that, comparable to other FTLD/ALS genes, SQSTM1 mutations are associated with TDP-43 pathology

Identification of Z-Tyr-Ala-CHN 2, a Cathepsin L Inhibitor with Broad-Spectrum Cell-Specific Activity against Coronaviruses, including SARS-CoV-2.

The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is partly under control by vaccination. However, highly potent and safe antiviral drugs for SARS-CoV-2 are still needed to avoid development of severe COVID-19. We report the discovery of a small molecule, Z-Tyr-Ala-CHN 2, which was identified in a cell-based antiviral screen. The molecule exerts sub-micromolar antiviral activity against SARS-CoV-2, SARS-CoV-1, and human coronavirus 229E. Time-of-addition studies reveal that Z-Tyr-Ala-CHN 2 acts at the early phase of the infection cycle, which is in line with the observation that the molecule inhibits cathepsin L. This results in antiviral activity against SARS-CoV-2 in VeroE6, A549-hACE2, and HeLa-hACE2 cells, but not in Caco-2 cells or primary human nasal epithelial cells since the latter two cell types also permit entry via transmembrane protease serine subtype 2 (TMPRSS2). Given their cell-specific activity, cathepsin L inhibitors still need to prove their value in the clinic; nevertheless, the activity profile of Z-Tyr-Ala-CHN 2 makes it an interesting tool compound for studying the biology of coronavirus entry and replication

No supportive evidence for TIA1 gene mutations in a European cohort of ALS-FTD spectrum patients

We evaluated the genetic contribution of the T cell-erestricted intracellular antigen-1 gene (TIA1) in a European cohort of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) patients. Exonic resequencing of TIA1 in 1120 patients (693 FTD, 341 ALS, 86 FTD-ALS) and 1039 controls identified in total 5 rare heterozygous missense variants, affecting the TIA1 low-complexity domain (LCD). Only 1 missense variant, p.Met290Thr, identified in a familial FTD patient with disease onset at 64 years, was absent from controls yet received a combined annotation-dependent depletion score of 11.42. By contrast, 3 of the 4 variants also detected in unaffected controls, p.Val294Glu, p.Gln318Arg, and p.Ala381Thr, had combined annotation-dependent depletion scores greater than 20. Our findings in a large European patient-control series indicate that variants in TIA1 are not a common cause of ALS and FTD. The observation of recurring TIA1 missense variants in unaffected individuals lead us to conclude that the exact genetic contribution of TIA1 to ALS and FTD pathogenesis remains to be further elucidated

Forward induction and entry deterrence: an experiment

The Dixit (Econ J 90:95–106, 1980) hypothesis that incumbents use investment in capacity to deter potential entrants has found little empirical support. Bagwell and Ramey (J Econ 27:660–680, 1996) propose a model where, in the unique game-theoretic prediction based on forward induction or iterated elimination of weakly-dominated strategies, the incumbent does not have the strategic advantage. We conduct an experiment with games inspired by these models. In the Dixit-style game, the incumbent monopolizes the market most of the time even without the investment in capacity. In our Bagwell-and-Ramey-style game, the incumbent also tends to keep the market, in contrast to the predictions of an entrant advantage. Nevertheless, we fin strong evidence that forward induction affects the behavior of most participants. The results of our games suggest that players perceive that the firs mover has an advantage without having to pre-commit capacity. In our Bagwell–Ramey game, evolution and learning do not drive out this perception. We back these claims with data analysis and a theoretical framework for dynamics.Publicad

VACCELERATE Site Network: Real-time definition of clinical study capacity in Europe

Background: The inconsistent European vaccine trial landscape rendered the continent of limited interest for vaccine developers. The VACCELERATE consortium created a network of capable clinical trial sites throughout Europe. VACCELERATE identifies and provides access to state-of-the-art vaccine trial sites to accelerate clinical development of vaccines. Methods: Login details for the VACCELERATE Site Network (vaccelerate.eu/site-network/) questionnaire can be obtained after sending an email to. Interested sites provide basic information, such as contact details, affiliation with infectious disease networks, main area of expertise, previous vaccine trial experience, site infrastructure and preferred vaccine trial settings. In addition, sites can recommend other clinical researchers for registration in the network. If directly requested by a sponsor or sponsor representative, the VACCELERATE Site Network pre-selects vaccine trial sites and shares basic study characteristics provided by the sponsor. Interested sites provide feedback with short surveys and feasibility questionnaires developed by VACCELERATE and are connected with the sponsor to initiate the site selection process. Results: As of April 2023, 481 sites from 39 European countries have registered in the VACCELERATE Site Network. Of these, 137 (28.5 %) sites have previous experience conducting phase I trials, 259 (53.8 %) with phase II, 340 (70.7 %) with phase III, and 205 (42.6 %) with phase IV trials, respectively. Infectious diseases were reported as main area of expertise by 274 sites (57.0 %), followed by any kind of immunosuppression by 141 (29.3 %) sites. Numbers are super additive as sites may report clinical trial experience in several indications. Two hundred and thirty-one (47.0 %) sites have the expertise and capacity to enrol paediatric populations and 391 (79.6 %) adult populations. Since its launch in October 2020, the VACCELERATE Site Network has been used 21 times for academic and industry trials, mostly interventional studies, focusing on different pathogens such as fungi, monkeypox virus, Orthomyxoviridae/influenza viruses, SARS-CoV-2, or Streptococcus pneumoniae/pneumococcus. Conclusions: The VACCELERATE Site Network enables a constantly updated Europe-wide mapping of experienced clinical sites interested in executing vaccine trials. The network is already in use as a rapid-turnaround single contact point for the identification of vaccine trials sites in Europe.The VACCELERATE Site Network has received funding from the European Union’s Horizon 2020 research and innovation pro gramme (grant agreement No 101037867) and the German Federal Ministry of Education and Research (Bundesministerium für Bil dung und Forschung [BMBF]) (grant agreement No BMBF01KX2040).S

The effects of postharvest carbon dioxide and a cold storage treatment on Tuta absoluta mortality and tomato fruit quality

Tuta absoluta is an invasive pest species that affects tomatoes and other solanaceous crops and is found in Europe and other Mediterranean areas. Hitherto, fumigation with methyl bromide is the only measure used to control this pest during the postharvest period. Because of methyl bromide phytotoxicity and health, safety and environmental concerns, alternatives to this product need to be investigated. Therefore, the objective of this study was to determine the ability of T. absoluta to complete its preimaginal development on tomato fruit during the postharvest period and to evaluate the effectiveness of different supra atmospheric carbon dioxide (CO2) levels and cold storage treatments on T. absoluta control. T. absoluta was unable to complete its development from egg to adult on fruit of three tomato varieties. In contrast, T. absoluta completed its preimaginal development when more mature larvae were provided with the tomato fruit. The exposure of T. absoluta to a modified atmosphere of 95% CO2 at 25 °C for 48 h was effective for the control of all life stages, but negatively affect fruit quality. An increment in the exposure time to 72 h was necessary in order to obtain the same level of control at 40% CO2. A cold storage treatment at 1 °C for a total of 10 days was also effective for the control of the T. absoluta eggs. These two treatments did not negatively affect the quality of the fruit. Therefore, these appear to be effective alternatives to postharvest methyl bromide fumigation and future studies need to be planned to validate the commercial feasibility of these findings

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo