Interferon α kinoid induces neutralizing anti-interferon α antibodies that decrease the expression of interferon-induced and B cell activation associated transcripts: analysis of extended follow-up data from the interferon α kinoid phase I/II study.

IFN α Kinoid (IFN-K) is a therapeutic vaccine composed of IFNα2b coupled to a carrier protein. In a phase I/II placebo-controlled trial, we observed that IFN-K significantly decreases the IFN gene signature in whole blood RNA samples from SLE patients. Here, we analysed extended follow-up data from IFN-K-treated patients, in order to evaluate persistence of neutralizing anti-IFNα Abs antibodies (Abs), and gene expression profiling. Serum and whole blood RNA samples were obtained in IFN-K-treated patients included in the follow-up study, in order to determine binding and neutralizing anti-IFNα Ab titres, and perform high-throughput transcriptomic studies. Neutralization studies of 13 IFNα subtypes demonstrated the polyclonal nature of the Ab response induced by IFN-K. Follow-up analyses in six patients confirmed a significant correlation between neutralizing anti-IFNα Ab titres and decrease in IFN scores compared to baseline. These analyses also revealed an inhibitory effect of IFNα blockade on the expression of B cell associated transcripts. IFN-K induces a polyclonal anti-IFNα response that decreases IFN- and B cell-associated transcripts. ClinicalTrials.gov, clinicaltrials.gov, NCT01058343

Efficacy, safety, and pharmacokinetics of the anti-programmed cell death receptor-1 (PD-1) monoclonal antibody, tislelizumab (BGB-A317) in a phase 2, open-label, multicenter study to investigate in patients with unresectable hepatocellular carcinoma - Trial in progress.

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real world dosing of regorafenib reg in metastatic colorectal cancer mcrc final results from the prospective observational correlate study

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Power losses in thick steel laminations with hysteresis

Magnetic power losses have been experimentally investigated and theoretically predicted over a range of frequencies (direct current—1.5 kHz) and peak inductions (0.5-1.5 T) in 1‐mm‐thick FeSi 2 wt. % laminations. The direct current hysteresis properties of the system are described by the Preisach model, with the Preisach distribution function reconstructed from the measurement of the recoil magnetization curve (Bp=1.7 T). On this basis, the time behavior of the magnetic induction vs frequency at different lamination depths is calculated by a finite element method numerical solution of Maxwell equations, which takes explicitly into account the Preisach model hysteretic B(H) relationship. The computed loop shapes are, in general, in good agreement with the measured ones. The power loss dependence on frequency is predicted and experimentally found to change from a ∼f3/2 to a ∼f2 law with increasing peak induction

TERMINAL FLOWER-1/CENTRORADIALIS inhibits tuberization via protein interaction with the tuberigen activation complex

This work was funded by the Scottish Government Rural and Environment Science and Analytical Services Division as part of the Strategic Research Programme 2016-2021, by a GCRF Foundation Awards for Global Agricultural and Food Systems Research funded by the BBSRC project BB/P022553/1 and also received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement number 835704. Research in Prat’s lab was funded by the Spanish Ministerio de Economía y Competitividad BIO2015-73019-EXP, and the aligned Japan EIG CONCERT (PIA102017-1) projects.Potato tuber formation is a secondary developmental program by which cells in the subapical stolon region divide and radially expand, to further differentiate into starch accumulating parenchyma. Whilst some details of the molecular pathway that signals tuberization are known, important gaps in our knowledge persist. Here the role of a member of the TERMINAL FLOWER 1/ CENTRORADIALIS gene family (termed StCEN ) in the negative control of tuberization is demonstrated for the first time. It is shown that reduced expression of StCEN accelerates tuber formation whereas transgenic lines over‐expressing this gene display delayed tuberization and reduced tuber yield. Protein‐protein interaction studies (yeast two hybrid and bimolecular fluorescence complementation) demonstrate that StCEN binds components of the recently described tuberigen activation complex. Using transient transactivation assays we show that the StSP6A tuberization signal is an activation target of the tuberigen activation complex, and that co‐expression of StCEN blocks StFD‐Like‐1 activation of the StSP6A gene. Transcriptomic analysis of transgenic lines mis‐expressing StCEN identify early transcriptional events in tuber formation. These results demonstrate that StCEN suppresses tuberization by directly antagonizing StSP6A function in stolons, identifying StCEN as a breeding marker to improve tuber initiation and yield, through the selection of genotypes with reduced StCEN expression.Publisher PDFPeer reviewe

Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes

Dysfunctional skeletal muscle calcium homeostasis plays a central role in the pathophysiology of several human and animal skeletal muscle disorders, in particular, genetic disorders associated with ryanodine receptor 1 (RYR1) mutations, such as malignant hyperthermia, central core disease, multiminicore disease and certain centronuclear myopathies. In addition, aberrant skeletal muscle calcium handling is believed to play a pivotal role in the highly prevalent disorder of Thoroughbred racehorses, known as Recurrent Exertional Rhabdomyolysis. Traditionally, such defects were studied in human and equine subjects by examining the contractile responses of biopsied muscle strips exposed to caffeine, a potent RYR1 agonist. However, this test is not widely available and, due to its invasive nature, is potentially less suitable for valuable animals in training or in the human paediatric setting. Furthermore, increasingly, RYR1 gene polymorphisms (of unknown pathogenicity and significance) are being identified through next generation sequencing projects. Consequently, we have investigated a less invasive test that can be used to study calcium homeostasis in cultured, skin-derived fibroblasts that are converted to the muscle lineage by viral transduction with a MyoD (myogenic differentiation 1) transgene. Similar models have been utilised to examine calcium homeostasis in human patient cells, however, to date, there has been no detailed assessment of the cells’ calcium homeostasis, and in particular, the responses to agonists and antagonists of RYR1. Here we describe experiments conducted to assess calcium handling of the cells and examine responses to treatment with dantrolene, a drug commonly used for prophylaxis of recurrent exertional rhabdomyolysis in horses and malignant hyperthermia in humans

Проектирование системы хранения и внутрицеховой транспортировки печатных плат

С учетом принципов модульности, эргономичности и функциональности в проекте разработана система хранения и внутрицеховой транспортировки печатных плат, соответствующая современным стилям и направлениям промышленного дизайна.Taking into account the principles of modularity, ergonomics and functionality in the technologies of storage and in-house transportation of printed circuit boards corresponding to modern styles and directions of industrial design