Cation-induced changes in the inner- and outer-sphere mechanisms of electrocatalytic CO2 reduction.

The underlying mechanism of cation effects on CO2RR remains debated. Herein, we study cation effects by simulating both outer-sphere electron transfer (OS-ET) and inner-sphere electron transfer (IS-ET) pathways during CO2RR via constrained density functional theory molecular dynamics (cDFT-MD) and slow-growth DFT-MD (SG-DFT-MD), respectively. Our results show without any cations, only OS-ET is feasible with a barrier of 1.21 eV. In the presence of K+ (Li+), OS-ET shows a very high barrier of 2.93 eV (4.15 eV) thus being prohibited. However, cations promote CO2 activation through IS-ET with the barrier of only 0.61 eV (K+) and 0.91 eV (Li+), generating the key intermediate (adsorbed CO[Formula: see text]). Without cations, CO2-to-CO[Formula: see text](ads) conversion cannot proceed. Our findings reveal cation effects arise from short-range Coulomb interactions with reaction intermediates. These results disclose that cations modulate the inner- and outer-sphere pathways of CO2RR, offering substantial insights on the cation specificity in the initial CO2RR steps.

Structure and energetics of liquid water-hydroxyl layers on Pt(111).

The interactions between liquid water and hydroxyl species on Pt(111) surfaces have been intensely investigated due to their importance to fuel cell electrocatalysis. Here we present a molecular dynamics study of their structure and energetics using an ensemble of neural network potentials, which allow us to obtain unprecedented statistical sampling. We first study the energetics of hydroxyl formation, where we find a near-linear adsorption energy profile, which exhibits a soft and gradual increase in the differential adsorption energy at high hydroxyl coverages. This is strikingly different from the predictions of the conventional bilayer model, which displays a kink at 1/3ML OH coverage indicating a sizeable jump in differential adsorption energy, but within the statistical uncertainty of previously reported ab initio molecular dynamics studies. We then analyze the structure of the interface, where we provide evidence for the water-OH/Pt(111) interface being hydrophobic at high hydroxyl coverages. We furthermore explain the observed adsorption energetics by analyzing the hydrogen bonding in the water-hydroxyl adlayers, where we argue that the increase in differential adsorption energy at high OH coverage can be explained by a reduction in the number of hydrogen bonds from the adsorbed water molecules to the hydroxyls.

[Evaluation of Weaning Success in Long-Term Invasively Ventilated Patients at a Weaning Center]. / Ergebnisse der Re-Evaluation von Patienten aus der Intensivpflege in einem lokalen Weaning-Zentrum.

Despite the use of enormous personnel and other resources in German weaning centers, approximately 20 % of patients currently fail to get weaned from mechanical ventilation (MV) and need out-of-hospital ventilation.Between 03/2015 and 11/2019, we carried out a pilot project with 33 patients (48 % female, mean age 68 ±â€Š11 years at hospital admission) in order to re-evaluate their options of a possible weaning from MV. At this stage the patients had been invasively ventilated for 475 ±â€Š775 days. The mean stay in our weaning center was 26 ±â€Š19 days. 24/33 (73.53 %) patients were successfully weaned from MV. Of those, 11/24 (44 %) were discharged with non-invasive out-of-hospital ventilation. The completely weaned patients had a survival period of 3 or 12 months (92 % and 77 %), respectively. In those discharged with non-invasive ventilation, the survival period of 3 or months was 91 % and 81 %, respectively. In those discharged with invasive ventilation, this was 86 % and 71 %, respectively.The current results demonstrate that even those undergoing long-term out-of-hospital invasive ventilation can be successfully weaned from MV. Therefore, we suggest regular re-evaluations of weaning opportunities in invasively ventilated ambulatory patients.

Parameters predicting COVID-19-induced myocardial injury and mortality.

Clinical manifestations of COVID-19 affect many organs, including the heart. Cardiovascular disease is a dominant comorbidity and prognostic factors predicting risk for critical courses are highly needed. Moreover, immunomechanisms underlying COVID-induced myocardial damage are poorly understood. OBJECTIVE: To elucidate prognostic markers to identify patients at risk. RESULTS: Only patients with pericardial effusion (PE) developed a severe disease course, and those who died could be identified by a high CD8/Treg/monocyte ratio. Ten out of 19 COVID-19 patients presented with PE, 7 (78%) of these had elevated APACHE-II mortality risk-score, requiring mechanical ventilation. At admission, PE patients showed signs of systemic and cardiac inflammation in NMR and impaired cardiac function as detected by transthoracic echocardiography (TTE), whereas parameters of myocardial injury e.g. high sensitive troponin-t (hs-TnT) were not yet increased. During the course of disease, hs-TnT rose in 8 of the PE-patients above 16 ng/l, 7 had to undergo ventilatory therapy and 4 of them died. FACS at admission showed in PE patients elevated frequencies of CD3+CD8+ T cells among all CD3+ T-cells, and lower frequencies of Tregs and CD14+HLA-DR+-monocytes. A high CD8/Treg/monocyte ratio predicted a severe disease course in PE patients, and was associated with high serum levels of antiviral cytokines. By contrast, patients without PE and PE patients with a low CD8/Treg/monocyte ratio neither had to be intubated, nor died. CONCLUSIONS: PE predicts cardiac injury in COVID-19 patients. Therefore, TTE should be performed at admission. Immunological parameters for dysfunctional antiviral immunity, such as the CD8/Treg/monocyte ratio used here, supports risk assessment by predicting poor prognosis.

[Prevalence and treatment of rheumatological adverse events due to immune checkpoint inhibitor therapy]. / Prävalenz und Therapie von rheumatologischen Nebenwirkungen bei Immun-Checkpoint-Inhibitor-Therapie.

BACKGROUND: Immune checkpoint inhibitors (ICI) have essentially improved the treatment options for various malignant diseases. They lead to an activation of the immune system and subsequent attack of tumor cells by affecting the immune system and preventing tumor cells from avoiding detection. In addition to this desired effect, immune-related adverse events (irAE) can occur in nearly all organ systems and therefore also rheumatological irAE (rh-irAE). OBJECTIVE: The occurrence of rh-irAE has been described in various publications and is specifically investigated in this review. The aim is to provide an overview on the prevalence, severity, treatment options and altered tumor response in patients with rh-irAE. MATERIAL AND METHODS: We conducted a literature search for studies and case reports on rh-irAE under ICI therapy in PubMed up to January 2020 using the PICO model. RESULTS: A total of 18 publications were included, most of which were clinical studies (n = 13) and the rest case reports (n = 5). Several rh-irAE can occur with a wide variety of manifestations of which arthralgia, arthritis and myositis were the most common. Other rheumatic diseases, such as vasculitis, connective tissue diseases and sarcoidosis were less frequently described. The published prevalence of rh-irAE varied with a prevalence between 2.3% and 6.6%. Treatment of rh-irAE depends on the severity and most patients receive nonsteroidal anti-inflammatory drugs and glucocorticosteroids. In some cases, conventional DMARDs, such as methotrexate and biological DMARDs, were administered. Patients with rh-irAE in general had a higher tumor response rate compared to patients without side effects. CONCLUSION: A close observation of patients and early detection of rh-irAE are important in order to treat these side effects in time. Further prospective studies are necessary to systematically investigate rh-irAE.

Improving the Activity of M-N4 Catalysts for the Oxygen Reduction Reaction by Electrolyte Adsorption.

Metal and nitrogen codoped carbons (M-N/Cs) have emerged as promising alternatives to platinum-based catalysts for the oxygen reduction reaction (ORR). DFT calculations are used to investigate the adsorption of anions and impurities from the electrolyte on the active site, modeled as an M-N4 motif embedded in a planar carbon sheet (M=Cr, Mn, Fe, Co). The two-dimensional catalyst structure implies that each metal atom has two potential active sites, one on each side of the sheet. Adsorption of anions or impurities on both sites results in poisoning, but adsorption on one of the sites leads to a modified ORR activity on the remaining site. The calculated adsorption energies show that a number of species adsorb only on one of the two sites under realistic experimental conditions. Furthermore, a few of these adsorbates modify the adsorption energies of the ORR intermediates on the remaining site, in such a way that the limiting potential is improved.

Optimized Ki-67 staining in murine cells: a tool to determine cell proliferation.

The reliable analysis of the cell cycle status has become increasingly relevant for scientific and clinical work, especially for the determination of tumor cell growth. One established method to characterize the proliferation activity of cells is the analysis of the Ki-67 protein. Ki-67 is expressed in the nucleus during the whole cell cycle except for the G0 phase. Several different protocols exist for the examination of the Ki-67 protein in tissue and cell culture, but most of them are defined for human cells. For the analysis of the Ki-67 protein in murine tissue and cell culture there is a variety of protocols existing which recommend different fixation and permeabilization reagents or special kits. In this study, we established a reliable protocol for Ki-67 staining in murine cells and tissue based on PFA fixation, which can be used not only for flow cytometry but also for immunofluorescence microscopy analysis. We tested our protocol successfully with three different Ki-67 anti-mouse antibodies in cell culture, regenerating liver tissue and mouse melanoma tumor to demonstrate the general applicability.

Combined DFT and Differential Electrochemical Mass Spectrometry Investigation of the Effect of Dopants in Secondary Zinc-Air Batteries.

Zinc-air batteries offer the potential of low-cost energy storage with high specific energy, but at present secondary Zn-air batteries suffer from poor cyclability. To develop economically viable secondary Zn-air batteries, several properties need to be improved: choking of the cathode, catalyzing the oxygen evolution and reduction reactions, limiting dendrite formation and suppressing the hydrogen evolution reaction (HER). Understanding and alleviating HER at the negative electrode in a secondary Zn-air battery is a substantial challenge, for which it is necessary to combine computational and experimental research. Here, we combine differential electrochemical mass spectrometry (DEMS) and density functional theory (DFT) calculations to investigate the fundamental role and stability when cycling in the presence of selected beneficial additives, that is, In and Bi, and Ag as a potentially unfavorable additive. We show that both In and Bi have the desired property for a secondary battery, that is, upon recharging they will remain on the surface, thereby retaining the beneficial effects on Zn dissolution and suppression of HER. This is confirmed by DEMS, where it is observed that In reduces HER and Bi affects the discharge potential beneficially compared to a battery without additives. Using a simple procedure based on adsorption energies calculated with DFT, it is found that Ag suppresses OH adsorption, but, unlike In and Bi, it does not hinder HER. Finally, it is shown that mixing In and Bi is beneficial compared to the additives by themselves as it improves the electrochemical performance and cyclic stability of the secondary Zn-air battery.

Giant onsite electronic entropy enhances the performance of ceria for water splitting.

Previous studies have shown that a large solid-state entropy of reduction increases the thermodynamic efficiency of metal oxides, such as ceria, for two-step thermochemical water splitting cycles. In this context, the configurational entropy arising from oxygen off-stoichiometry in the oxide, has been the focus of most previous work. Here we report a different source of entropy, the onsite electronic configurational entropy, arising from coupling between orbital and spin angular momenta in lanthanide f orbitals. We find that onsite electronic configurational entropy is sizable in all lanthanides, and reaches a maximum value of ≈4.7 k B per oxygen vacancy for Ce4+/Ce3+ reduction. This unique and large positive entropy source in ceria explains its excellent performance for high-temperature catalytic redox reactions such as water splitting. Our calculations also show that terbium dioxide has a high electronic entropy and thus could also be a potential candidate for solar thermochemical reactions.Solid-state entropy of reduction increases the thermodynamic efficiency of ceria for two-step thermochemical water splitting. Here, the authors report a large and different source of entropy, the onsite electronic configurational entropy arising from coupling between orbital and spin angular momenta in f orbitals.

[Weaning Unit of the University Medicine Greifswald - Institutional Structure and Weaning Results from Prolonged Ventilation over 10 Years]. / Weaningzentrum Greifswald ­ Struktur und Ergebnisse bei der Entwöhnung von der Langzeitbeatmung über zehn Jahre.

The increasing importance of intensive care medicine including mechanical ventilation has been accompanied by the demand of weaning opportunities for patients undergoing prolonged mechanical ventilation. Consequently, specialised clinical institutions, focusing on the weaning from mechanical ventilation, have been established since the 1980 s.The present article illustrates the structural development and results of such a specialised institution at the University Medicine Greifswald, using data of 616 patients collected within the past ten years (2006 - 2015). Across the years, a shift in the underlying disease leading to mechanical ventilation can be found, with rising numbers of patients suffering from pneumonia/sepsis and declining numbers of patients who underwent cardiac surgery in advance. The days with mechanical ventilation outside (p = 0.004) and within the investigated institution (p = 0.02) are significantly declining. The percentage of successfully weaned patients increased from 62.7 % (2006 - 2010) to 77.3 % (2011 - 2015), p < 0.001. Consecutively, the percentage of patients who remained mechanically ventilated decreased from 16.4 % to 9.6 % (p < 0.001) and the share of in-hospital deceased patients significantly declined from 20.9 % to 13.0 % (p < 0.001). Furthermore, the one-year-survival after hospital discharge in successful weaned patients was 72 percent. The present data, collected at the University Medicine Greifswald are quite comparable to data of other German institutions that are specialised on weaning from mechanical ventilation.

MicroRNA-146a reduces MHC-II expression via targeting JAK/STAT signaling in dendritic cells after stem cell transplantation.

Acute Graft-versus-host disease (GVHD) is a major immunological complication after allogeneic hematopoietic cell transplantation and a better understanding of the molecular regulation of the disease could help to develop novel targeted therapies. Here we found that a G/C polymorphism within the human microRNA-146a (miR-146a) gene of transplant recipients, which causes reduced miR-146a levels, was strongly associated with the risk of developing severe acute GVHD (n=289). In mice, deficiency of miR-146a in the hematopoietic system or transfer of recipient-type miR-146a-/- dendritic cells (DCs) enhanced GVHD, while miR-146a mimic-transfected DCs ameliorated disease. Mechanistically, lack of miR-146a enhanced JAK2-STAT1 pathway activity, which led to higher expression of class II-transactivator (CIITA) and consecutively increased MHCII-levels on DCs. Inhibition of JAK1/2 or CIITA knockdown in DCs prevented miR-146a-/- DC-induced GVHD exacerbation. Consistent with our findings in mice, patients with the miR-146a polymorphism rs2910164 in hematopoietic cells displayed higher MHCII levels on monocytes, which could be targeted by JAK1/2 inhibition. Our findings indicate that the miR-146a polymorphism rs2910164 identifies patients at high risk for GVHD before allo-HCT. Functionally we show that miR-146a acts as a central regulator of recipient-type DC activation during GVHD by dampening the pro-inflammatory JAK-STAT/CIITA/MHCII axis, which provides a scientific rationale for early JAK1/2 inhibition in selected patients.

Descriptors and Thermodynamic Limitations of Electrocatalytic Carbon Dioxide Reduction on Rutile Oxide Surfaces.

A detailed understanding of the electrochemical reduction of CO2 into liquid fuels on rutile metal oxide surfaces is developed by using DFT calculations. We consider oxide overlayer structures on RuO2 (1 1 0) surfaces as model catalysts to elucidate the trends and limitations in the CO2 reduction reaction (CO2RR) based on thermodynamic analysis. We aim to specify the requirements for CO2RR catalysts to establish adsorbate scaling relations and use these to derive activity volcanoes. Computational results show that the OH* binding free energy is a good descriptor of the thermodynamic limitations and it defines the left leg of the activity volcano for CO2RR. HCOOH* is a key intermediate for products formed through further reduction, for example, methanediol, methanol, and methane. The surfaces that do not bind HCOOH* are selective towards formic acid (HCOOH) production, but hydrogen evolution limits their suitability. We determine the ideal binding free energy for H* and OH* to facilitate selective CO2RR over H2 /CO evolution to be ΔGB [H]>0.5 eV and -0.5 eV<ΔGB [OH]<0.1 eV. The Re-containing overlayers considered in this work display excellent promise for selectivity, although they are active at a highly reducing potential.

Decoupling strain and ligand effects in ternary nanoparticles for improved ORR electrocatalysis.

Ternary Pt-Au-M (M = 3d transition metal) nanoparticles show reduced OH adsorption energies and improved activity for the oxygen reduction reaction (ORR) compared to pure Pt nanoparticles, as obtained by density functional theory. The strain and ligand effects in nanoparticles are decoupled and correlated with the extended Pt(111) surface for benchmarking. The ternary metal in the core allows for tuning the catalytic activity through strain effects. Pt-Au-M for M = Cr, Mn, Co, Cu, Zn nanoparticles are of particular interest as they exhibit an optimal contribution of strain, ligand effects and stability. Good agreement is found with experimental studies showing increased activity of Pt-Au-Fe/Ni nanoparticles, and mid to late 3d transition metals are predicted to exhibit enhance activity and stability with respect to pure Pt nanoparticles.

Development of Hemolytic Anemia in a Nivolumab-Treated Patient with Refractory Metastatic Squamous Cell Skin Cancer and Chronic Lymphatic Leukemia.

Management of patients with metastatic squamous cell skin cancer, refractory to initial therapy with standard chemotherapy and radiation protocols, remains difficult with poor overall prognosis and limited therapeutic options. Recently, promising response rates with nivolumab, a programmed death receptor-1-blocking antibody, in squamous cancer of the head and neck have been demonstrated. Considering the similar histological patterns of squamous cell cancer of the skin and squamous cell cancer of the head and neck, we assumed that nivolumab could also be effective in our patients with refractory metastatic squamous cell cancer of the skin. So far, there have been no clinical data on the therapeutic efficacy of nivolumab in squamous cell skin cancer. We here present a case of a patient with metastatic squamous cell skin cancer refractory to previous therapies, who showed a good response to nivolumab over a period of 5 months, but developed a serious hemolytic crisis under nivolumab treatment after eight applications.

Competition between Kondo Screening and Quantum Hall Edge Reconstruction.

We report on a Kondo correlated quantum dot connected to two-dimensional leads where we demonstrate the renormalization of the g factor in the pure Zeeman case. i.e., for magnetic fields parallel to the plane of the quantum dot. For the same system, we study the influence of orbital effects by investigating the quantum Hall regime; i.e., a perpendicular magnetic field is applied. In this case an unusual behavior of the suppression of the Kondo effect and of the split zero-bias anomaly is observed. The splitting decreases with magnetic field and shows discontinuous changes that are attributed to the intricate interplay between Kondo screening and the quantum Hall edge structure originating from electrostatic screening. This edge structure, made up of compressible and incompressible stripes, strongly affects the Kondo temperature of the quantum dot and thereby influences the renormalized g factor.

Selective Electrochemical Generation of Hydrogen Peroxide from Water Oxidation.

Water is a life-giving source, fundamental to human existence, yet over a billion people lack access to clean drinking water. The present techniques for water treatment such as piped, treated water rely on time and resource intensive centralized solutions. In this work, we propose a decentralized device concept that can utilize sunlight to split water into hydrogen and hydrogen peroxide. The hydrogen peroxide can oxidize organics while the hydrogen bubbles out. In enabling this device, we require an electrocatalyst that can oxidize water while suppressing the thermodynamically favored oxygen evolution and form hydrogen peroxide. Using density functional theory calculations, we show that the free energy of adsorbed OH* can be used to determine selectivity trends between the 2e(-) water oxidation to H2O2 and the 4e(-) oxidation to O2. We show that materials which bind oxygen intermediates sufficiently weakly, such as SnO2, can activate hydrogen peroxide evolution. We present a rational design principle for the selectivity in electrochemical water oxidation and identify new material candidates that could perform H2O2 evolution selectively.

A DFT-based genetic algorithm search for AuCu nanoalloy electrocatalysts for CO2 reduction.

Using a DFT-based genetic algorithm (GA) approach, we have determined the most stable structure and stoichiometry of a 309-atom icosahedral AuCu nanoalloy, for potential use as an electrocatalyst for CO2 reduction. The identified core-shell nano-particle consists of a copper core interspersed with gold atoms having only copper neighbors and a gold surface with a few copper atoms in the terraces. We also present an adsorbate-dependent correction scheme, which enables an accurate determination of adsorption energies using a computationally fast, localized LCAO-basis set. These show that it is possible to use the LCAO mode to obtain a realistic estimate of the molecular chemisorption energy for systems where the computation in normal grid mode is not computationally feasible. These corrections are employed when calculating adsorption energies on the Cu, Au and most stable mixed particles. This shows that the mixed Cu135@Au174 core-shell nanoalloy has a similar adsorption energy, for the most favorable site, as a pure gold nano-particle. Cu, however, has the effect of stabilizing the icosahedral structure because Au particles are easily distorted when adding adsorbates.

Elucidating the activity of stepped Pt single crystals for oxygen reduction.

The unexpectedly high measured activity of Pt[n(111) × (111)] and Pt[n(111) × (100)] stepped single crystal surfaces towards the oxygen reduction reaction (ORR) is explained utilizing the hydroxyl binding energy as the activity descriptor. Using this descriptor (estimated using experimental data obtained by different groups), a well-defined Sabatier-type volcano is observed for the activities measured for the Pt[n(111) × (111)] and Pt[n(111) × (100)] stepped single crystals, in remarkable agreement with earlier theoretical studies. We propose that the observed destabilisation of *OH species at these surfaces is due to the decreased solvation of the adsorbed hydroxyl intermediates on adjacent terrace sites.