Design of a 55 W packaged GaN HEMT with 60% PAE by internal matching in S-band

International audienceThis paper reports a package synthesis method in order to ensure good performances in PAE, output power and bandwidth. The internal matching circuits of the optimized package enable to reach the best impedance pre-matching at fundamental frequencies and also to confine the harmonic impedances seen by the internal GaN power bar into safe-efficiency regions whatever the external impedances presented to the package at second harmonic frequencies. In a 50Ω environment, the packaged GaN HEMT delivers 55 W output power associated with 60% PAE and 13.3 dB power gain at 2.7 GHz. By optimizing source and load impedances at the fundamental frequencies, the packaged GaN HEMT demonstrates more than 58% PAE from 2.6 GHz to 3.0 GHz

The FAIR Guiding Principles for scientific data management and stewardship

There is an urgent need to improve the infrastructure supporting the reuse of scholarly data. A diverse set of stakeholders—representing academia, industry, funding agencies, and scholarly publishers—have come together to design and jointly endorse a concise and measureable set of principles that we refer to as the FAIR Data Principles. The intent is that these may act as a guideline for those wishing to enhance the reusability of their data holdings. Distinct from peer initiatives that focus on the human scholar, the FAIR Principles put specific emphasis on enhancing the ability of machines to automatically find and use the data, in addition to supporting its reuse by individuals. This Comment is the first formal publication of the FAIR Principles, and includes the rationale behind them, and some exemplar implementations in the community

Finite element pressure stabilizations for incompressible flow problems

Discretizations of incompressible flow problems with pairs of finite element spaces that do not satisfy a discrete inf-sup condition require a so-called pressure stabilization. This paper gives an overview and systematic assessment of stabilized methods, including the respective error analysis

CD36 and Fyn kinase mediate malaria-induced lung endothelial barrier dysfunction in mice infected with Plasmodium berghei.

PMC3744507Severe malaria can trigger acute lung injury characterized by pulmonary edema resulting from increased endothelial permeability. However, the mechanism through which lung fluid conductance is altered during malaria remains unclear. To define the role that the scavenger receptor CD36 may play in mediating this response, C57BL/6J (WT) and CD36-/- mice were infected with P. berghei ANKA and monitored for changes in pulmonary endothelial barrier function employing an isolated perfused lung system. WT lungs demonstrated a >10-fold increase in two measures of paracellular fluid conductance and a decrease in the albumin reflection coefficient (σalb) compared to control lungs indicating a loss of barrier function. In contrast, malaria-infected CD36-/- mice had near normal fluid conductance but a similar reduction in σalb. In WT mice, lung sequestered iRBCs demonstrated production of reactive oxygen species (ROS). To determine whether knockout of CD36 could protect against ROS-induced endothelial barrier dysfunction, mouse lung microvascular endothelial monolayers (MLMVEC) from WT and CD36-/- mice were exposed to H2O2. Unlike WT monolayers, which showed dose-dependent decreases in transendothelial electrical resistance (TER) from H2O2 indicating loss of barrier function, CD36-/- MLMVEC demonstrated dose-dependent increases in TER. The differences between responses in WT and CD36-/- endothelial cells correlated with important differences in the intracellular compartmentalization of the CD36-associated Fyn kinase. Malaria infection increased total lung Fyn levels in CD36-/- lungs compared to WT, but this increase was due to elevated production of the inactive form of Fyn further suggesting a dysregulation of Fyn-mediated signaling. The importance of Fyn in CD36-dependent endothelial signaling was confirmed using in vitro Fyn knockdown as well as Fyn-/- mice, which were also protected from H2O2- and malaria-induced lung endothelial leak, respectively. Our results demonstrate that CD36 and Fyn kinase are critical mediators of the increased lung endothelial fluid conductance caused by malaria infection.JH Libraries Open Access Fun

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Peptides in the gas phase: from structure to electronic dynamics

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Introduction: Bond Specific Spectroscopy of Peptides and Proteins

International audienceFrom the early days of peptide and protein investigations, vibrational spectroscopy has occupied a special place among the physical chemistry methods used, thanks to its intrinsic capability to resolve vibrational features due to covalent bonds and its sensitivity upon the environment of these bonds, in particular H-bonding. Due to the size of these systems, however, traditional spectroscopy often faces crowded features, from which relevant information, in particular spectroscopic assignment, is difficult to extract. Spectroscopists, however, have taken up the challenge, relying on various, often multidimensional strategies to overcome the effects of complexity, depending upon the environment of the molecules studied, i.e., solution, thin films, or even gas phase. Reviews in this special issue, together with a few others recently published, illustrate the various instrumental strategies developed, the recent trends in the corresponding fields, and their applications to model or real systems.In the condensed phase, one of the keys to specificity is to rely on spatial selectivity, e.g., by selecting the environment of the proteins observed, through a surface-sensitive diagnostic, like surface-enhanced Vibrational Sum-Frequency Generation (Weidner) or by focusing on specific probes of the system, e.g. chiral centers, interrogated through Vibrational Optical Activity measurements (Keiderling) or by an external perturbation, related to the function of the molecule, and monitoring the change through Infrared Difference Spectroscopy (Lorenz-Fonfria). Alternatively, multidimensional spectroscopy can also be implemented, e.g. 2D-IR (1) and also Resonance Raman Spectroscopy (Hildebrandt), whose diagnostic selectivity stems from electronic states of the system. Most importantly, many of these techniques, amenable to pump–probe experiments, have the benefit of time resolution, at various time scales, depending upon the physics of the interaction, allowing us to successfully document both the corresponding structural changes and the dynamics of the systems studied: reaction centers in proteins, protein folding, structural dynamics of interfacial proteins, etc.In the gas phase, the lack of sensitivity has led experimentalists to turn to so-called action spectroscopies, where the IR absorption is monitored through changes in the system, e.g., fragmentation (IR-induced multiphoton dissociation) of ionic species (2) or ground state depopulation of cold neutrals (IR/UV double resonance experiments) (submitted for consideration is a paper by Gerhards et al.). During the past decades, these efforts benefited from the development of laser vaporization, electrospray ionization techniques, and exquisite spectral resolutions can be achieved thanks to efficient cooling in supersonic expansion for neutrals or in cryogenic traps for ions. (3,4) Availability of new IR sources, including table-top parametric oscillators and free electron lasers, whose range now attains the THz region (Rijs), also greatly contributed to the success of this field. The selectivity achieved in the gas phase experiments paved the way to conformation-specific IR spectroscopy, which was even further improved for charged species, through a coupling with ion mobility spectroscopy. (5) Applications encompass the assessment of H-bond strengths in peptides, competition issues within the conformational landscape of small peptides, their aggregation (submitted for consideration is a paper by Gerhards et al.), or their slow backbone motions (Rijs), etc. IR multiphoton dissociation, coupled to mass spectrometry, is also used to characterize ions through action spectroscopy. (2,6,7) Despite its lack of conformational selectivity, it turns out to be of uttermost interest to characterize structural details of biological significance, e.g. to monitor the post-translational modifications borne by the peptides under scrutiny (Fornarini). Finally, gas phase studies also enable pump–probe experiments, where the reactive processes following a UV photon absorption can be characterized, in particular their dependence upon the structure (Grégoire). Specific excited state dynamical processes find applications in mass spectrometry, for an advanced characterization and analysis of charged peptides and more generally of biomolecules (Brodbelt).Needless to say that these impressive experimental developments all benefited from an active synergy with theoretical advances in ground state structural and vibrational modeling (8) and in the quantum chemistry description of electronic excited states (9) and of their dynamics. (10) Particularly obvious is the cross fertilization of quantum chemistry modeling and “spectroscopic grade” gas phase experiments.This thematic issue provides an overview of recent developments and results, covering a broad range of vibrational spectroscopic methods. It is organized according to the size of the systems treated and to their environment, going from neutral gas phase model systems, peptide ions, peptides in solution, to proteins.I would like to thank the Editor, Professor Joachim Heberle, for his encouragements, his team for their efficient support, as well as all the authors for their contributions, and wish the reader pleasure and enjoyment along this promenade in the vibrational landscape of peptides and proteins