A Class-E-Based Resonant AC-DC Converter With Inherent PFC Capability

This paper investigates the use of the class-E inverter for power factor correction (PFC) applications. Analytical and state-space models are derived showing the class-E inverter’s capability of achieving inherent PFC operation with a constant duty cycle. The inherent PFC operation limits the controller responsibility to the regulation of the output voltage, which is key for resonant converters with challenging control. A converter incorporating a diode bridge, a class-E inverter, and a class-D rectifier is presented for the PFC stage in single-phase offline converters. A prototype is designed to validate the analysis and presented design method. The prototype operates with zero-voltage switching (ZVS) across the load range and achieves up to 211 W of output power at an efficiency of 88%, with an inherent power factor of 0.99 and a total harmonic distortion (THD) of 8.8 %. Frequency modulation is used to achieve lower output power down to 25 W, with a power factor of 0.95, THD of 28 %, and an efficiency of 88 %

H2 as a fuel for flavin- and H2O2-dependent biocatalytic reactions

The soluble hydrogenase from Ralstonia eutropha provides an atom efficient regeneration system for reduced flavin cofactors using H2 as an electron source. We demonstrated this system for highly selective ene-reductase-catalyzed C[double bond, length as m-dash]C-double bond reductions and monooxygenase-catalyzed epoxidation. Reactions were expanded to aerobic conditions to supply H2O2 for peroxygenase-catalyzed hydroxylations.DFG, 284111627, H2-basierende Kaskaden für die Biosynthese von N-HeterocyclenDFG, 405325648, ,Engineering von O2-toleranten Hydrogenasen und ihre physiologischen Auswirkungen in rekombinanten Bakterien im Hinblick auf die Hydrogenase-abhängige NAD(P)H-Regeneration und H2-ProduktionDFG, 390540038, EXC 2008: UniSysCatTU Berlin, Open-Access-Mittel - 202

A clinical tool for predicting survival in ALS

Background: Amyotrophic lateral sclerosis (ALS) is a progressive and usually fatal neurodegenerative disease. Survival from diagnosis varies considerably. Several prognostic factors are known, including site of onset (bulbar or limb), age at symptom onset, delay from onset to diagnosis and the use of riluzole and non-invasive ventilation (NIV). Clinicians and patients would benefit from a practical way of using these factors to provide an individualised prognosis. Methods: 575 consecutive patients with incident ALS from a population-based registry in South-East England register for ALS (SEALS) were studied. Their survival was modelled as a two-step process: the time from diagnosis to respiratory muscle involvement, followed by the time from respiratory involvement to death. The effects of predictor variables were assessed separately for each time interval. Findings: Younger age at symptom onset, longer delay from onset to diagnosis and riluzole use were associated with slower progression to respiratory involvement, and NIV use was associated with lower mortality after respiratory involvement, each with a clinically significant effect size. Riluzole may have a greater effect in younger patients and those with longer delay to diagnosis. A patient's survival time has a roughly 50% chance of falling between half and twice the predicted median. Interpretation: A simple and clinically applicable graphical method of predicting an individual patient's survival from diagnosis is presented. The model should be validated in an independent cohort, and extended to include other important prognostic factors

Latent cluster analysis of ALS phenotypes identifies prognostically differing groups

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a degenerative disease predominantly affecting motor neurons and manifesting as several different phenotypes. Whether these phenotypes correspond to different underlying disease processes is unknown. We used latent cluster analysis to identify groupings of clinical variables in an objective and unbiased way to improve phenotyping for clinical and research purposes. METHODS Latent class cluster analysis was applied to a large database consisting of 1467 records of people with ALS, using discrete variables which can be readily determined at the first clinic appointment. The model was tested for clinical relevance by survival analysis of the phenotypic groupings using the Kaplan-Meier method. RESULTS The best model generated five distinct phenotypic classes that strongly predicted survival (p<0.0001). Eight variables were used for the latent class analysis, but a good estimate of the classification could be obtained using just two variables: site of first symptoms (bulbar or limb) and time from symptom onset to diagnosis (p<0.00001). CONCLUSION The five phenotypic classes identified using latent cluster analysis can predict prognosis. They could be used to stratify patients recruited into clinical trials and generating more homogeneous disease groups for genetic, proteomic and risk factor research

Novel mutations support a role for Profilin 1 in the pathogenesis of ALS

AbstractMutations in the gene encoding profilin 1 (PFN1) have recently been shown to cause amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. We sequenced the PFN1 gene in a cohort of ALS patients (n = 485) and detected 2 novel variants (A20T and Q139L), as well as 4 cases with the previously identified E117G rare variant (∼ 1.2%). A case-control meta-analysis of all published E117G ALS+/− frontotemporal dementia cases including those identified in this report was significant p = 0.001, odds ratio = 3.26 (95% confidence interval, 1.6–6.7), demonstrating this variant to be a susceptibility allele. Postmortem tissue from available patients displayed classic TAR DNA-binding protein 43 pathology. In both transient transfections and in fibroblasts from a patient with the A20T change, we showed that this novel PFN1 mutation causes protein aggregation and the formation of insoluble high molecular weight species which is a hallmark of ALS pathology. Our findings show that PFN1 is a rare cause of ALS and adds further weight to the underlying genetic heterogeneity of this disease

Predicting the future of ALS: the impact of demographic change and potential new treatments on the prevalence of ALS in the United Kingdom, 2020-2116

OBJECTIVE To model the effects of demographic change under various scenarios of possible future treatment developments in ALS. METHODS Patients diagnosed with ALS at the King's College Hospital Motor Nerve Clinic between 2004 and 2017, and living within the London boroughs of Lambeth, Southwark, and Lewisham (LSL), were included as incident cases. We also ascertained incident cases from the Canterbury region over the same period. Future incidence of ALS was estimated by applying the calculated age- and sex-specific incidence rates to the UK population projections from 2020 to 2116. The number of prevalent cases for each future year was estimated based on an established method. Assuming constant incidence, we modelled four possible future prevalence scenarios by altering the median disease duration for varying subsets of the population, to represent the impact of new treatments. RESULTS The total number of people newly diagnosed with ALS per year in the UK is projected to rise from a baseline of 1415 UK cases in 2010 to 1701 in 2020 and 2635 in 2116. Overall prevalence of ALS was predicted to increase from 8.58 per 100,000 persons in 2020 to 9.67 per 100,000 persons in 2116. Halting disease progression in patients with C9orf72 mutations would yield the greatest impact of the modelled treatment scenarios, increasing prevalence in the year 2066 from a baseline of 9.50 per 100,000 persons to 15.68 per 100,000 persons. CONCLUSIONS Future developments in treatment would combine with the effects of demographic change to result in more people living longer with ALS

The benefit of evolving multidisciplinary care in ALS: a diagnostic cohort survival comparison

BACKGROUND Care for people with amyotrophic lateral sclerosis (ALS) has altered at King's College Hospital over the last 20 years. The clinic has been a multidisciplinary, specialist, tertiary referral centre since 1995 with a large team with integrated palliative and respiratory care since 2006. We hypothesised that these changes would improve survival. METHODS In this retrospective observational study, patients diagnosed with El Escorial definite, probable and possible ALS between 1995-1998 and 2008-2011 were followed up. The primary outcome measure was a chi-square test for the proportion of each cohort surviving. Kaplan-Meier survival analysis and Cox multivariate regression were secondary analyses. RESULTS There was low reporting of some interventions. Five hundred and forty-seven people were included. Survival between the cohorts was significantly different (p = 0.022) with a higher proportion surviving during 2008-2011. Survival time was 21.6 (95% CI 19.2-24.0) months in the 2008-2011 cohort compared to 19.2 years (15.6-21.6) in the 1995-1998 cohort (log rank p = 0.018). Four hundred and ninety-three cases were included in the Cox regression. Diagnostic cohort was a significant predictor variable (HR 0.79 (0.64-0.97) p = 0.023). CONCLUSIONS These results support the hypothesis that integrated specialist clinics with multidisciplinary input improve survival in ALS

An adaptive delayed acknowledgment strategy to improve TCP performance in multi-hop wireless networks.

In multi-hop wireless networks, transmission control protocol (TCP) suffers from performance deterioration due to poor wireless channel characteristics. Earlier studies have shown that the small TCP acknowledgments consume as much wireless resources as the long TCP data packets. Moreover, generating an acknowledgment (ACK) for each incoming data packet reduces the performance of TCP. The main factor affecting TCP performance in multi-hop wireless networks is the contention and collision between ACK and data packets that share the same path. Thus, lowering the number of ACKs using the delayed acknowledgment option defined in IETF RFC 1122 will improve TCP performance. However, large cumulative ACKs will induce packet loss due to retransmission time-out at the sender side of TCP. Motivated by this understanding, we propose a new TCP receiver with an adaptive delayed ACK strategy to improve TCP performance in multi-hop wireless networks. Extensive simulations have been done to prove and evaluate our strategy over different topologies. The simulation results demonstrate that our strategy can improve TCP performance significantly

A comprehensive analysis of rare genetic variation in amyotrophic lateral sclerosis in the UK.

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of motor neurons. About 25 genes have been verified as relevant to the disease process, with rare and common variation implicated. We used next generation sequencing and repeat sizing to comprehensively assay genetic variation in a panel of known amyotrophic lateral sclerosis genes in 1126 patient samples and 613 controls. About 10% of patients were predicted to carry a pathological expansion of the C9orf72 gene. We found an increased burden of rare variants in patients within the untranslated regions of known disease-causing genes, driven by SOD1, TARDBP, FUS, VCP, OPTN and UBQLN2. We found 11 patients (1%) carried more than one pathogenic variant (P = 0.001) consistent with an oligogenic basis of amyotrophic lateral sclerosis. These findings show that the genetic architecture of amyotrophic lateral sclerosis is complex and that variation in the regulatory regions of associated genes may be important in disease pathogenesis