384 research outputs found
Odd Frequency Pairing in the Kondo Lattice
We discuss the possibility that heavy fermion superconductors involve
odd-frequency pairing of the kind first considered by Berezinskii. Using a toy
model for odd frequency triplet pairing in the Kondo lattice we are able to
examine key properties of this new type of paired state. To make progress
treating the strong constraint in the Kondo lattice model we use the
technical trick of a Majorana representation of the local moments, which
permits variational treatments of the model without a Gutzwiller approximation.
The simplest mean field theory involves the development of bound states between
the local moments and conduction electrons, characterized by a spinor order
parameter. We show that this state is a stable realization of odd frequency
triplet superconductivity with surfaces of gapless excitations whose spin and
charge coherence factors vanish linearly in the quasiparticle energy. A
NMR relaxation rate coexists with a linear specific heat. We discuss possible
extensions of our toy model to describe heavy fermion superconductivity.Comment: 67 page
Non-Coding Changes Cause Sex-Specific Wing Size Differences between Closely Related Species of Nasonia
The genetic basis of morphological differences among species is still poorly understood. We investigated the genetic basis of sex-specific differences in wing size between two closely related species of Nasonia by positional cloning a major male-specific locus, wing-size1 (ws1). Male wing size increases by 45% through cell size and cell number changes when the ws1 allele from N. giraulti is backcrossed into a N. vitripennis genetic background. A positional cloning approach was used to fine-scale map the ws1 locus to a 13.5 kilobase region. This region falls between prospero (a transcription factor involved in neurogenesis) and the master sex-determining gene doublesex. It contains the 5′-UTR and cis-regulatory domain of doublesex, and no coding sequence. Wing size reduction correlates with an increase in doublesex expression level that is specific to developing male wings. Our results indicate that non-coding changes are responsible for recent divergence in sex-specific morphology between two closely related species. We have not yet resolved whether wing size evolution at the ws1 locus is caused by regulatory alterations of dsx or prospero, or by another mechanism. This study demonstrates the feasibility of efficient positional cloning of quantitative trait loci (QTL) involved in a broad array of phenotypic differences among Nasonia species
Expert Elicitation on Wind Farm Control
Wind farm control is an active and growing field of research in which the
control actions of individual turbines in a farm are coordinated, accounting
for inter-turbine aerodynamic interaction, to improve the overall performance
of the wind farm and to reduce costs. The primary objectives of wind farm
control include increasing power production, reducing turbine loads, and
providing electricity grid support services. Additional objectives include
improving reliability or reducing external impacts to the environment and
communities. In 2019, a European research project (FarmConners) was started
with the main goal of providing an overview of the state-of-the-art in wind
farm control, identifying consensus of research findings, data sets, and best
practices, providing a summary of the main research challenges, and
establishing a roadmap on how to address these challenges. Complementary to the
FarmConners project, an IEA Wind Topical Expert Meeting (TEM) and two rounds of
surveys among experts were performed. From these events we can clearly identify
an interest in more public validation campaigns. Additionally, a deeper
understanding of the mechanical loads and the uncertainties concerning the
effectiveness of wind farm control are considered two major research gaps
Anemos : development of a next generation wind power forecasting system for the large-scale integration of onshore & offshore wind farms
International audienceThis paper presents the objectives and the research work carried out in the frame of the ANEMOS project on short-term wind power forecasting. The aim of the project is to develop accurate models that substantially outperform current state-of-the-art methods, for onshore and offshore wind power forecasting, exploiting both statistical and physical modeling approaches. The project focus on prediction horizons up to 48 hours ahead and investigates predictability of wind for higher horizons up to 7 days ahead useful i.e. for maintenance scheduling. Emphasis is given on the integration of highresolution meteorological forecasts. For the offshore case, marine meteorology is considered as well as information by satellite-radar images. An integrated software platform, ‘ANEMOS', is developed to host the various models. This system will be installed by several utilities for on-line operation at onshore and offshore wind farms for prediction at a local, regional and national scale. The applications include different terrain types and wind climates, on- and offshore cases, and interconnected or island grids. The on-line operation by the utilities will allow validation of the models and an analysis of the value of wind prediction for a competitive integration of wind energy in the developing liberalized electricity markets in the EU
Special Section on Pediatric Drug Disposition and Pharmacokinetics Role of Chromatin Structural Changes in Regulating Human CYP3A Ontogeny s
ABSTRACT Variability in drug-metabolizing enzyme developmental trajectories contributes to interindividual differences in susceptibility to chemical toxicity and adverse drug reactions, particularly in the first years of life. Factors linked to these interindividual differences are largely unknown, but molecular mechanisms regulating ontogeny are likely involved. To evaluate chromatin structure dynamics as a likely contributing mechanism, age-dependent changes in modified and variant histone occupancy were evaluated within known CYP3A4 and 3A7 regulatory domains. Chromatin immunoprecipitation using fetal or postnatal human hepatocyte chromatin pools followed by quantitative polymerase chain reaction DNA amplification was used to determine relative chromatin occupancy by modified and variant histones. Chromatin structure representing a poised transcriptional state (bivalent chromatin), indicated by the occupancy by modified histones associated with both active and repressed transcription, was observed for CYP3A4 and most 3A7 regulatory regions in both postnatal and fetal livers. However, the CYP3A4 regulatory regions had significantly greater occupancy by modified histones associated with repressed transcription in the fetal liver. Conversely, some modified histones associated with active transcription exhibited greater occupancy in the postnatal liver. CYP3A7 regulatory regions also had significantly greater occupancy by modified histones associated with repressed transcription in the fetus. The observed occupancy by modified histones is consistent with chromatin structural dynamics contributing to CYP3A4 ontogeny, although the data are less conclusive regarding CYP3A7. Interpretation of the latter data may be confounded by celltype heterogeneity in the fetal liver
Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia
We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20-27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67-4.31) and improved OS (HR=0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data
International Society for Extracellular Vesicles and International Society for Cell and Gene Therapy statement on extracellular vesicles from mesenchymal stromal cells and other cells: considerations for potential therapeutic agents to suppress coronavirus disease-19
STATEMENT: The International Society for Cellular and Gene Therapies (ISCT) and the International Society for Extracellular Vesicles (ISEV) recognize the potential of extracellular vesicles (EVs, including exosomes) from mesenchymal stromal cells (MSCs) and possibly other cell sources as treatments for COVID-19. Research and trials in this area are encouraged. However, ISEV and ISCT do not currently endorse the use of EVs or exosomes for any purpose in COVID-19, including but not limited to reducing cytokine storm, exerting regenerative effects or delivering drugs, pending the generation of appropriate manufacturing and quality control provisions, pre-clinical safety and efficacy data, rational clinical trial design and proper regulatory oversight
Next Generation Short-Term Forecasting of Wind Power – Overview of the ANEMOS Project.
International audienceThe aim of the European Project ANEMOS is to develop accurate and robust models that substantially outperform current state-of-the-art methods, for onshore and offshore wind power forecasting. Advanced statistical, physical and combined modelling approaches were developed for this purpose. Priority was given to methods for on-line uncertainty and prediction risk assessment. An integrated software platform, 'ANEMOS', was developed to host the various models. This system is installed by several end-users for on-line operation and evaluation at a local, regional and national scale. Finally, the project demonstrates the value of wind forecasts for the power system management and market integration of wind power. Keywords: Wind power, short-term forecasting, numerical weather predictions, on-line software, tools for wind integration
Perinatal Derivatives: Where Do We Stand? A Roadmap of the Human Placenta and Consensus for Tissue and Cell Nomenclature
Progress in the understanding of the biology of perinatal tissues has contributed to the
breakthrough revelation of the therapeutic effects of perinatal derivatives (PnD), namely
birth-associated tissues, cells, and secreted factors. The significant knowledge acquired
in the past two decades, along with the increasing interest in perinatal derivatives, fuels
an urgent need for the precise identification of PnD and the establishment of updated
consensus criteria policies for their characterization. The aim of this review is not to go into detail on preclinical or clinical trials, but rather we address specific issues
that are relevant for the definition/characterization of perinatal cells, starting from an
understanding of the development of the human placenta, its structure, and the different
cell populations that can be isolated from the different perinatal tissues. We describe
where the cells are located within the placenta and their cell morphology and phenotype.
We also propose nomenclature for the cell populations and derivatives discussed herein.
This review is a joint effort from the COST SPRINT Action (CA17116), which broadly
aims at approaching consensus for different aspects of PnD research, such as providing
inputs for future standards for the processing and in vitro characterization and clinical
application of PnD.Austrian Science Fund (FWF)
DOC 31-B26Medical University GrazUniversita Cattolica del Sacro CuorePRIN 2017 program of Italian Ministry of Research and University (MIUR)
2017RSAFK7Ministry of Health, Italy
GR-2018-12366992Slovenian Research Agency - Slovenia
P3-0108MRIC UL
IP-0510Plan Estatal de Investigacion Cientifica y Tecnica y de InnovacionISCIII Subdireccion General de Evaluacion y Fomento de la InvestigacionMinisterio de Economia y Competitividad, Spain
PI16/01642European Union (EU)European Community (EC)German Research Foundation (DFG)
GE-2223/2-
The Mast Cell Degranulator Compound 48/80 Directly Activates Neurons
Background
Compound 48/80 is widely used in animal and tissue models as a “selective” mast cell activator. With this study we demonstrate that compound 48/80 also directly activates enteric neurons and visceral afferents.
Methodology/Principal Findings
We used in vivo recordings from extrinsic intestinal afferents together with Ca++ imaging from primary cultures of DRG and nodose neurons. Enteric neuronal activation was examined by Ca++ and voltage sensitive dye imaging in isolated gut preparations and primary cultures of enteric neurons. Intraluminal application of compound 48/80 evoked marked afferent firing which desensitized on subsequent administration. In egg albumen-sensitized animals, intraluminal antigen evoked a similar pattern of afferent activation which also desensitized on subsequent exposure to antigen. In cross-desensitization experiments prior administration of compound 48/80 failed to influence the mast cell mediated response. Application of 1 and 10 µg/ml compound 48/80 evoked spike discharge and Ca++ transients in enteric neurons. The same nerve activating effect was observed in primary cultures of DRG and nodose ganglion cells. Enteric neuron cultures were devoid of mast cells confirmed by negative staining for c-kit or toluidine blue. In addition, in cultured enteric neurons the excitatory action of compound 48/80 was preserved in the presence of histamine H1 and H2 antagonists. The mast cell stabilizer cromolyn attenuated compound 48/80 and nicotine evoked Ca++ transients in mast cell-free enteric neuron cultures.
Conclusions/Significance
The results showed direct excitatory action of compound 48/80 on enteric neurons and visceral afferents. Therefore, functional changes measured in tissue or animal models may involve a mast cell independent effect of compound 48/80 and cromolyn
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