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Reference model guided system design and implementation for interoperable environmental research infrastructures

Environmental research infrastructures (RIs) support their respective research communities by integrating large-scale sensor/observation networks with data curation services, analytical tools and common operational policies. These RIs are developed as pillars of intra-and interdisciplinary research, however comprehension of the complex, pathologically interconnected aspects of the Earth's ecosyste

Distribution functions of magnetic nanoparticles determined by a numerical inversion method

In the present study, we applied a regularized inversion method to extract the particle size, magnetic moment and relaxation-time distribution of magnetic nanoparticles from small-angle x-ray scattering (SAXS), DC magnetization (DCM) and AC susceptibility (ACS) measurements. For the measurements the particles were colloidally dispersed in water. At first approximation the particles could be assume

NNT reverse mode of operation mediates glucose control of mitochondrial NADPH and glutathione redox state in mouse pancreatic β-cells

Objective: The glucose stimulation of insulin secretion (GSIS) by pancreatic β-cells critically depends on increased production of metabolic coupling factors, including NADPH. Nicotinamide nucleotide transhydrogenase (NNT) typically produces NADPH at the expense of NADH and δpH in energized mitochondria. Its spontaneous inactivation in C57BL/6J mice was previously shown to alter ATP production, Ca

The advantage of laser-capture microdissection over whole tissue analysis in proteomic profiling studies

Laser-capture microdissection (LCM) offers a reliable cell population enrichment tool and has been successfully coupled to MS analysis. Despite this, most proteomic studies employ whole tissue lysate (WTL) analysis in the discovery of disease biomarkers and in profiling analyses. Furthermore, the influence of tissue heterogeneity in WTL analysis, nor its impact in biomarker discovery studies have

How do leaf and ecosystem measures of water-use efficiency compare?

The terrestrial carbon and water cycles are intimately linked: the carbon cycle is driven by photosynthesis, while the water balance is dominated by transpiration, and both fluxes are controlled by plant stomatal conductance. The ratio between these fluxes, the plant water-use efficiency (WUE), is a useful indicator of vegetation function. WUE can be estimated using several techniques, including l

Ligand-independent G protein-coupled estrogen receptor/G protein-coupled receptor 30 activity : Lack of receptor-dependent effects of G-1 and 17b-estradiol

G protein-coupled receptor 30 (GPR30) is a membrane receptor reported to bind 17b-estradiol (E2) and mediate rapid nongenomic estrogen responses, hence also named G protein-coupled estrogen receptor. G-1 is a proposed GPR30-specific agonist that has been used to implicate the receptor in several pathophysiological events. However, controversy surrounds the role of GPR30 in G-1 and E2 responses. We

MET Expression and Cancer Stem Cell Networks Impact Outcome in High-Grade Serous Ovarian Cancer

Overexpression of the receptor tyrosine kinase MET has been linked to poor survival in several cancer types, and MET has been suggested to interact with stem cell networks. In vitro studies have further suggested a possible benefit of a combined treatment using PARP and MET inhibitors. We used a tissue microarray (TMA) with 130 samples of advanced-stage high-grade serous fallopian tube/ovarian can

Integration of remote sensing and Mexican water quality monitoring system using an extreme learning machine

Remote Sensing, as a driver for water management decisions, needs further integration with monitoring water quality programs, especially in developing countries. Moreover, usage of remote sensing approaches has not been broadly applied in monitoring routines. Therefore, it is necessary to assess the efficacy of available sensors to complement the often limited field measurements from such programs

EMA Review of Daratumumab (Darzalex) for the Treatment of Adult Patients Newly Diagnosed with Multiple Myeloma

The use of daratumumab in combination with established regimens for the treatment of newly diagnosed multiple myeloma has recently been authorized by the European Medicines Agency based on results from three separate phase III randomized, active controlled, open-label studies that have confirmed enhanced efficacy and tolerability in both transplant-ineligible (MMY3008 and MMY3007) and transplant-e

Therapeutic Recommendations for the Management of Older Adult Patients with Sjögren’s Syndrome

Primary Sjögren’s syndrome (SjS) is a systemic autoimmune disease most commonly diagnosed in middle-aged women. Although the disease can occur at all ages, it is diagnosed between 30 and 60 years of age in two-thirds of patients. In more than 20% of cases, the people are older than 65 years. In this review, we focus on the therapeutic management of primary SjS in older patients, following the rece

Pathological drivers of neurodegeneration in suspected non-Alzheimer’s disease pathophysiology

Background: Little is known about the heterogeneous etiology of suspected non-Alzheimer’s pathophysiology (SNAP), a group of subjects with neurodegeneration in the absence of β-amyloid. Using antemortem MRI and pathological data, we investigated the etiology of SNAP and the association of neurodegenerative pathologies with structural medial temporal lobe (MTL) measures in β-amyloid-negative subjec

Probing the Néel-Type Antiferromagnetic Order and Coherent Magnon–Exciton Coupling in Van Der Waals VPS3

2D van der Waals (vdW) antiferromagnets have received intensive attention due to their terahertz resonance, multilevel magnetic-order states, and ultrafast spin dynamics. However, accurately identifying their magnetic configuration still remains a challenge owing to the lack of net magnetization and insensitivity to external fields. In this work, the Néel-type antiferromagnetic (AFM) order in 2D a

Parkin absence accelerates microtubule aging in dopaminergic neurons

Loss-of-function caused by mutations in the parkin gene (PARK2) lead to early-onset familial Parkinson's disease. Recently, mechanistic studies proved the ability of parkin in regulating mitochondria homeostasis and microtubule (MT) stability. Looking at these systems during aging of PARK2 knockout mice, we found that loss of parkin induced an accelerated (over)acetylation of MT system both in dop

TANGO2 deficiency as a cause of neurodevelopmental delay with indirect effects on mitochondrial energy metabolism

Exome sequencing has recently identified mutations in the gene TANGO2 (transport and Golgi organization 2) as a cause of developmental delay associated with recurrent crises involving rhabdomyolysis, cardiac arrhythmias, and metabolic derangements. The disease is not well understood, in part as the cellular function and subcellular localization of the TANGO2 protein remain unknown. Furthermore, th

Assessment of the appropriate use criteria for amyloid PET in an unselected memory clinic cohort : The ABIDE project

Introduction: The objective of this study was to assess the usefulness of the appropriate use criteria (AUC) for amyloid imaging in an unselected cohort. Methods: We calculated sensitivity and specificity of appropriate use (increased confidence and management change), as defined by Amyloid Imaging Taskforce in the AUC, and other clinical utility outcomes. Furthermore, we compared differences in p

Intensity-dependent near-threshold ionization of Kr in the vacuum-uv

In this work, we present measurements of the intensity-dependent photoelectron spectrum of Kr irradiated by the FLASH FEL tuned to a photon energy of 25.8 eV. Intensity dependent photoelectron spectra were obtained with the aid of a Velocity Map Imaging (VMI) spectrometer. As the FEL photon energy is close to threshold, two photon sequential double ionization is favoured. The number of open channe

Discordant amyloid-β PET and CSF biomarkers and its clinical consequences

Background: In vivo, high cerebral amyloid-β load has been associated with (i) reduced concentrations of Aβ42 in cerebrospinal fluid and (ii) increased retention using amyloid-β positron emission tomography. Although these two amyloid-β biomarkers generally show good correspondence, ~ 10-20% of cases have discordant results. To assess the consequences of having discordant amyloid-β PET and CSF bio

Geospatial mapping of surgical systems for earthquake emergency planning in Guerrero, Mexico : an ecological study

BACKGROUND: Accessibility to surgical services can impact earthquake preparedness and response. We aimed to estimate the population with timely access to surgical care in Guerrero, a Mexican state with high tectonic activity, and identify populations at risk in the event of an earthquake.METHODS: We conducted an ecological study using open government data. We extracted data from Guerrero municipal

Role of serotype and virulence determinants of Streptococcus pyogenes biofilm bacteria in internalization and persistence in epithelial cells in vitro.

Streptococcus pyogenes causes a multitude of local and systemic infections, the most common being pharyngitis in children. Recurrent pharyngeal infections are common and are thought to be due to the re-emergence of intracellular GAS upon completion of antibiotic treatment. The role of colonizing biofilm bacteria in this process is not fully clear. Here, live respiratory epithelial cells were inoc

Movement disorders and nonmotor neuropsychological symptoms in children and adults with classical galactosemia

Although movement disorders (MDs) are known complications, the exact frequency and severity remains uncertain in patients with classical galactosemia, especially in children. We determined the frequency, classification and severity of MDs in a cohort of pediatric and adult galactosemia patients, and assessed the association with nonmotor neuropsychological symptoms and daily functioning. Patients