Coordination and organometallic precursors of group 10 and 11 Focused electron beam induced deposition of metals and insight gained from chemical vapour deposition, atomic layer deposition, and fundamental surface and gas phase studies

Nanostructured materials made from group 10 Ni, Pd, Pt and group 11 Cu, Ag, Au elements have outstanding technological relevance in microelectronics, nano optics, catalysis, and energy conversion. Processes that allow for the easy and reliable fabrication of such nanostructures are heavily sought after. Focused electron beam induced deposition FEBID is the only direct write technique that can fabricate nanostructures with arbitrary shape and dimensions down to the sub 10 nm regime. However, the complex chemistry of FEBID involving electron induced dissociation processes of metalorganic precursors molecules, surface kinetics, and thermal effects is poorly understood and far from being optimized. Here, we review in a comparative manner the performance and the underlying chemical reactions of surface deposition processes, namely, chemical vapour deposition CVD , atomic layer deposition ALD , and FEBID itself. The knowledge gained in CVD and ALD as related surface deposition techniques will help us to understand the spatially selective chemistry occurring in FEBID. Fundamental surface and gas phase studies provide insight to electron induced chemistry and desorption of precursor fragments. Specific emphasis is put on the type of the ligands and their different behaviour under thermal, surface related, and electron induced processes. The comprehensive overview of the current state of FEBID for group 10 and 11 metals includes reactive environments and purification approaches as these may provide valuable information on the design of novel precursors. The evaluation of the precursor and process performance is extended to include W, Co, Fe, Ru, Rh, and Ir to represent a general guide towards future developments in FEBID. These may not only rely on the design of novel compounds but also on optimized deposition strategies inspired by ALD and CV

Research Staff COVID-19 Pandemic Survey-Results from the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network

Objectives: There is a lack of knowledge about the challenges of researchers who continued in-person research during the early phases of the COVID-19 pandemic. Design: Electronic survey assessing work-related exposure to COVID-19, logistical challenges, and procedural changes during the first year of the COVID-19 pandemic on clinical research. Setting: National Heart, Lung, and Blood Institute-sponsored Prevention and Early Treatment of Acute Lung Injury Clinical Trial Network Centers. Subjects: Research staff at research Network Sites. Measurements and Main Results: The 37-question survey was completed by 277 individuals from 24 states between 29 September 2020, and 12 December 2020, yielding a response rate of 37.7%. Most respondents (91.5%) indicated that non-COVID-19 research was affected by COVID-19 research studies. In response to the COVID-19 pandemic, 20% of respondents were reassigned to different roles at their institution. Many survey takers were exposed to COVID-19 (56%), with more than 50% of researchers requiring a COVID-19 test and 8% testing positive. The fear of infection was 2.7-times higher compared to pre-COVID-19 times. Shortages of personal protective equipment were encountered by 34% of respondents, primarily due to lack of access to N95 masks, followed by gowns and protective eyewear. Personal protective equipment reallocation from research to clinical use was reported by 31% of respondents. Most of the respondents (88.5%), despite these logistical challenges, indicated their willingness to enroll COVID-19 patients. Conclusions: During the first year of the COVID-19 pandemic, members of the research network were engaged in COVID-19 research despite logistical challenges, limited access to personal protective equipment, and fear of exposure. The research network’s survey experience can inform ongoing policy discussions to create research enterprises that can dexterously refocus research to address the knowledge gaps associated with novel public health emergencies while mitigating the effect of pandemics on existing research projects and research personnel

Enzyme Promiscuity in Enolase Superfamily. Theoretical Study of o-Succinylbenzoate Synthase Using QM/MM Methods

The promiscuous activity of the enzyme o-succinylbenzoate synthase (OSBS) from the actinobacteria Amycolatopsis is investigated by means of QM/MM methods, using both density functional theory and semiempirical Hamiltonians. This enzyme catalyzes not only the dehydration of 2-succinyl-6R-hydroxy-2,4-cyclohexadiene-1R-carboxylate but also catalyzes racemization of different acylamino acids, with N-succinyl-R-phenylglycine being the best substrate. We investigated the molecular mechanisms for both reactions exploring the potential energy surface. Then, molecular dynamics simulations were performed to obtain the free energy profiles and the averaged interaction energies of enzymatic residues with the reacting system. Our results confirm the plausibility of the reaction mechanisms proposed in the literature, with a good agreement between theoretical and experimentally derived activation free energies. Our simulations unravel the role played by the different residues in each of the two possible reactions. The presence of flexible loops in the active site and the selection of structural modifications in the substrate seem to be key elements to promote the promiscuity of this enzyme.This work was supported by the Spanish Ministerio de Economia y Competitividad project CTQ2012-36253-C03-03 ́ and FEDER funds. K.S. thanks the Polish National Science Center (NCN) for Grant 2011/02/A/ST4/00246. The authors acknowledge computational facilities of the Servei d’Informatica ̀ de la Universitat de Valencia in the ̀ “Tirant” supercomputer, which is part of the Spanish Supercomputing Network

Protein kinase C α and ε phosphorylation of troponin and myosin binding protein C reduce Ca2+ sensitivity in human myocardium

Previous studies indicated that the increase in protein kinase C (PKC)-mediated myofilament protein phosphorylation observed in failing myocardium might be detrimental for contractile function. This study was designed to reveal and compare the effects of PKCα- and PKCε-mediated phosphorylation on myofilament function in human myocardium. Isometric force was measured at different [Ca2+] in single permeabilized cardiomyocytes from failing human left ventricular tissue. Activated PKCα and PKCε equally reduced Ca2+ sensitivity in failing cardiomyocytes (ΔpCa50 = 0.08 ± 0.01). Both PKC isoforms increased phosphorylation of troponin I- (cTnI) and myosin binding protein C (cMyBP-C) in failing cardiomyocytes. Subsequent incubation of failing cardiomyocytes with the catalytic subunit of protein kinase A (PKA) resulted in a further reduction in Ca2+ sensitivity, indicating that the effects of both PKC isoforms were not caused by cross-phosphorylation of PKA sites. Both isozymes showed no effects on maximal force and only PKCα resulted in a modest significant reduction in passive force. Effects of PKCα were only minor in donor cardiomyocytes, presumably because of already saturated cTnI and cMyBP-C phosphorylation levels. Donor tissue could therefore be used as a tool to reveal the functional effects of troponin T (cTnT) phosphorylation by PKCα. Massive dephosphorylation of cTnT with alkaline phosphatase increased Ca2+ sensitivity. Subsequently, PKCα treatment of donor cardiomyocytes reduced Ca2+ sensitivity (ΔpCa50 = 0.08 ± 0.02) and solely increased phosphorylation of cTnT, but did not affect maximal and passive force. PKCα- and PKCε-mediated phosphorylation of cMyBP-C and cTnI as well as cTnT decrease myofilament Ca2+ sensitivity and may thereby reduce contractility and enhance relaxation of human myocardium

Transcendental-Phenomenological Proof and Descriptive Metaphysics

Following P.F. Strawson's reading of Kant, the majority of the literature on transcendental arguments seeks to divorce such arguments from their original Kantian context. This thesis is concerned with Mark Sacks's recent defence of transcendental arguments, which takes a different approach. A critique is given of Sacks's work and extensions and modifications of his approach are recommended. It is proposed that certain difficulties encountered by Kant's transcendentally-ideal approach can be overcome with Hegelian solutions

Parametry jakości plemników samców myszy z czterech outbredowych linii selekcyjnych

Breeding of (outbred) selective lines of laboratory mouse was initiated in Warsaw University of Life Sciences about 40 years ago. It bred Heavy (C) and Light (L) mice selected opposite for body weight at weaning (21st day of life), S mice line selected for higher testes weight, and control (K) mice without selection. All lines have identical genetic background, but different directions of selections caused diversification of specific phe-notypic traits between them. The purpose of this study was to compare semen quantity and quality parameters in outbred C, K, L and S male mice in the context of measurements of average body and testes weight for each line. Research materials were seminal fluids squeezed out of the vas deferens from 20 outbred C, K, L and S male mice (5 males per group). Animals had been euthanized, and necropsy was performed. Body and testes weight was measured. Also sperm concentration, viability (by Eosin test), cytoplasmic membrane integrity degree (HOS test), sperm head morphology and maturity were estimated. It was shown that S male mice, which have much higher testes weight, also have a significant increase of viable spermatozoa according to control line. Moreover, sperm concentration from S males is at least two times higher than in other selective lines.Parametry jakości plemników samców myszy z czterech outbredowych linii selekcyjnych. Celem przeprowadzonych badań było dokonanie oceny jakości parametrów plemników nasieniowodowych, pobranych od 20 samców (po 5 samców z linii) myszy z linii selekcjonowanych przez wiele pokoleń: przeciwstawnie na masę ciała (C i L), masę jąder (S) oraz samców stanowiących linię kontrolną (K), w kontekście pomiarów średnich mas ciała i jąder dla poszczególnych linii. Materiał badawczy stanowiły plemniki pobrane z nasieniowodów od zwierząt poselekcyjnych. Oszacowano liczbę plemników w 1 ml pożywki (M2). Dokonano analizy parametrów jakości plemników, wykonując test oceny żywotności plemników, test położenia kropli cytoplazmatycznej, który jest miarą dojrzałości plemników oraz test hipoosmotyczny (HOS) do oceny integralności błony cytoplazmatycznej witek plemników. Ponadto dokonano oceny morfologii główek plemników. Wykazano, że samce linii S w porównaniu z osobnikami z linii kontrolnej K oraz linii ciężkiej (C) i lekkiej (L) mają istotnie większą masę jąder, większy odsetek dojrzałych i żywotnych plemników, a także 2-4-krotnie większą koncentrację plemników liczoną w 1 ml medium