Solid-State Microwave Electronics

Contains reports on three research projects.National Aeronautics and Space Administration (Grant NGR-22-009-163

Solid-State Microwave Electronics

Contains reports on three research projects.National Aeronautics and Space Administration (Grant NGL 22-009-163)Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DA 28-043-AMC-02536(E

Solid-State Microwave Electronics

Contains reports on three research projects.National Aeronautics and Space Administration (Grant NGL-22-009-163)Joint Services Electronics Programs (U.S. Army, U.S. Navy, and U.S. Air Force)under Contract DA28-043-AMC-02536(E

Solid-State Microwave Electronics

Contains reports on status of research and nine research projects.National Aeronautics and Space Administration (Grant NGR-22-009-163

Solid-State Microwave Electronics

Contains research objectives and reports on status of research projects.National Aeronautics and Space Administration (Grant NGR-22-009-163

Highlights of the mini-symposium on extracellular vesicles in inter-organismal communication, held in Munich, Germany, August 2018

All living organisms secrete molecules for intercellular communication. Recent research has revealed that extracellular vesicles (EVs) play an important role in inter-organismal cell-to-cell communication by transporting diverse messenger molecules, including RNA, DNA, lipids and proteins. These discoveries have raised fundamental questions regarding EV biology. How are EVs biosynthesized and loaded with messenger/cargo molecules? How are EVs secreted into the extracellular matrix? What are the EV uptake mechanisms of recipient cells? As EVs are produced by all kind of organisms, from unicellular bacteria and protists, filamentous fungi and oomycetes, to complex multicellular life forms such as plants and animals, basic research in diverse model systems is urgently needed to shed light on the multifaceted biology of EVs and their role in inter-organismal communications. To help catalyse progress in this emerging field, a mini-symposium was held in Munich, Germany in August 2018. This report highlights recent progress and major questions being pursued across a very diverse group of model systems, all united by the question of how EVs contribute to inter-organismal communication

Sialylated N-glycans mediate monocyte uptake of extracellular vesicles secreted from Plasmodium falciparum-infected red blood cells

Glycoconjugates on extracellular vesicles (EVs) play a vital role in internalization and mediate interaction as well as regulation of the host immune system by viruses, bacteria, and parasites. During their intraerythrocytic life-cycle stages, malaria parasites, Plasmodium falciparum (Pf) mediate the secretion of EVs by infected red blood cells (RBCs) that carry a diverse range of parasitic and host-derived molecules. These molecules facilitate parasite-parasite and parasite-host interactions to ensure parasite survival. To date, the number of identified Pf genes associated with glycan synthesis and the repertoire of expressed glycoconjugates is relatively low. Moreover, the role of Pf glycans in pathogenesis is mostly unclear and poorly understood. As a result, the expression of glycoconjugates on Pf-derived EVs or their involvement in the parasite life-cycle has yet to be reported. Herein, we show that EVs secreted by Pf-infected RBCs carry significantly higher sialylated complex N-glycans than EVs derived from healthy RBCs. Furthermore, we reveal that EV uptake by host monocytes depends on N-glycoproteins and demonstrate that terminal sialic acid on the N-glycans is essential for uptake by human monocytes. Our results provide the first evidence that Pf exploits host sialylated N-glycans to mediate EV uptake by the human immune system cells

Bioequivalence study of 2.5 mg film-coated bisoprolol tablets in healthy volunteers

Wstęp: Bisoprolol jest jednym z najczęściej stosowanych beta-adrenolityków cechujących się kardioselektywnością i pozbawionym wewnętrznej aktywności sympatykomimetycznej. Jest powszechnie stosowany w leczeniu choroby niedokrwiennej serca czy niewydolności serca. Cel: Celem pracy była ocena równoważności biologicznej tabletek powlekanych zawierających bisoprolol w dawce 2,5 mg (Bisocard® — lek badany) w odniesieniu do oryginalnego produktu leczniczego (Concor Cor 2.5® — lek referencyjny). Metody: Przeprowadzono badanie otwarte z randomizacją w schemacie krzyżowym, po pojedynczym podaniu na czczo zdrowym ochotnikom rasy białej bisolprololu w dawce 10 mg (4 tabletki po 2,5 mg). Próbki krwi pobierano do 60. godziny po podaniu leku. Stężenie bisoprololu w osoczu oznaczono zwalidowaną metodą LC-MS/MS. Produkty lecznicze uznano za równoważne biologicznie, gdy 90-procentowe przedziały ufności (CI) stosunków średnich geometrycznych (produkt badany/referencyjny) dla zlogarytmowanych AUC(0–t), AUC(0–∞) i Cmax mieściły się w granicach 80–125%. Działania niepożądane monitorowano na podstawie parametrów klinicznych i zgłoszeń ochotników. Wyniki: Dwudziestu sześciu zdrowych ochotników obu płci (średnia wieku ok. 29 lat, wskaźnik masy ciała 22,7 kg/m2) zostało włączonych do badania, a 24 z nich ukończyło część kliniczną badania. Otrzymano następujące stosunki średnich geometrycznych (produkt badany/referencyjny): AUC(0–t) 95,16% (90% CI 92,52–97,87%), AUC(0–∞) 95,08% (90% CI 92,40–97,83%) oraz Cmax 100,00% (90% CI 94,83–105,45%). Nie zaobserwowano istotnych statystycznie różnic w ocenianych parametrach farmakokinetycznych między produktami badanym i referencyjnym. Nie stwierdzono poważnych zdarzeń niepożądanych w badanej populacji. Wnioski: W badanej populacji stwierdzono równoważność biologiczną leku generycznego (Bisocard®) z produktem referencyjnym (Concor Cor 2.5®). Oba produkty cechują się porównywalną, dobrą tolerancją i bezpieczeństwem.Background: Bisoprolol is one of the most widely used beta-blockers characterised by cardioselectivity, and it has no intrinsic sympathomimetic activity. It is commonly used in the treatment of coronary heart disease and heart failure.   Aim: The aim of study was to assess the bioequivalence of the film-coated tablets containing 2.5 mg of bisoprolol (Bisocard® — the medicinal product) to the original medicinal product (Concor Cor 2.5® — the reference).   Methods: A randomised, open-label, two-period, crossover, single-dose, relative bioavailability study was conducted in fasted healthy Caucasian volunteers. A single 10-mg oral dose (four tablets of 2.5 mg) of the test or reference product was followed by a 14-day wash-out period, after which the subjects received the alternative product. Blood was sampled within a period of 60 h post administration in pre-specified time points. Bisoprolol concentrations were determined by a validated LC-MS/MS method. The products were considered bioequivalent if the 90% confidence interval (CI) of the log-transformed geometric mean ratios (test vs. reference) for AUC(0–t), AUC(0–∞), and Cmax were within 80–125% limits. Adverse events were monitored during the study based on the subject claims and clinical parameters.   Results: Twenty-six healthy male and female volunteers (mean age ca. 29 years; body mass index 22.7 kg/m2) were in­cluded in the study, and 24 completed the clinical part. The geometric mean ratios (test/reference) for the log-transformed AUC(0–t), AUC(0–∞), and Cmax were 95.16% (90% CI 92.52–97.87%), 95.08% (90% CI 92.40–97.83%), and 100.00% (90% CI 94.83–105.45%), respectively. There were no significant differences in the pharmacokinetic parameters between the test and reference formulations. No serious adverse events were reported.   Conclusions: The results of this single-dose study in healthy Caucasian volunteers indicate that Bisocard®; 2.5 mg film-coated tablets are bioequivalent to the reference product — Concor Cor 2.5®; 2.5 mg film-coated tablets. Both products had similar safety profile and have been well tolerated.  

MuPix and ATLASPix -- Architectures and Results

High Voltage Monolithic Active Pixel Sensors (HV-MAPS) are based on a commercial High Voltage CMOS process and collect charge by drift inside a reversely biased diode. HV-MAPS represent a promising technology for future pixel tracking detectors. Two recent developments are presented. The MuPix has a continuous readout and is being developed for the Mu3e experiment whereas the ATLASPix is being developed for LHC applications with a triggered readout. Both variants have a fully monolithic design including state machines, clock circuitries and serial drivers. Several prototypes and design variants were characterised in the lab and in testbeam campaigns to measure efficiencies, noise, time resolution and radiation tolerance. Results from recent MuPix and ATLASPix prototypes are presented and prospects for future improvements are discussed.Comment: 10 pages, proceedings, The 28th International Workshop on Vertex Detectors (VERTEX 2019), 13 - 18 Oct 2019, Lopud Island, Croati