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Concurrent stem- and lineage-affiliated chromatin programs precede hematopoietic lineage restriction

The emerging notion of hematopoietic stem and progenitor cells (HSPCs) as a low-primed cloud without sharply demarcated gene expression programs raises the question on how cellular-fate options emerge and at which stem-like stage lineage priming is initiated. Here, we investigate single-cell chromatin accessibility of Lineage-, cKit+, and Sca1+ (LSK) HSPCs spanning the early differentiation landsc

Recommendations for addressing the translational gap between experimental and clinical research on amyloid diseases

This paper is a report of recommendations for addressing translational challenges in amyloid disease research. They were developed during and following an international online workshop organized by the LINXS Institute of Advanced Neutron and X-Ray Science in March 2021. Key suggestions include improving cross-cultural communication between basic science and clinical research, increasing the influe

Single-cell transcriptional profiling informs efficient reprogramming of human somatic cells to cross-presenting dendritic cells

Type 1 conventional dendritic cells (cDC1s) are rare immune cells critical for the induction of antigen-specific cytotoxic CD8+ T cells, although the genetic program driving human cDC1 specification remains largely unexplored. We previously identified PU.1, IRF8, and BATF3 transcription factors as sufficient to induce cDC1 fate in mouse fibroblasts, but reprogramming of human somatic cells was lim

LAG3 Regulates T Cell Activation and Plaque Infiltration in Atherosclerotic Mice

Background: The immune checkpoint receptor lymphocyte-activation gene 3 (LAG3) is a new target for immune checkpoint blockade (ICB), but the effects of LAG3 on atherosclerosis are not known. Objectives: The aim of the study was to evaluate the role of LAG3 on plaque inflammation using murine hypercholesterolemic models of atherosclerosis. Methods: To study the role of LAG3 in atherosclerosis, we i

Components of a healthy diet and different types of physical activity and risk of atherothrombotic ischemic stroke : A prospective cohort study

Background: Diet and physical activity (PA) are modifiable risk factors thought to influence the risk of ischemic stroke (IS). However, few studies have examined their effect on different subtypes of IS. Aim: To examine components of overall diet quality and different types of PA in relation to the risk of atherothrombotic IS (aIS). Materials and methods: The study population included 23,797 parti

Quantitative imaging by automated bone scan index (BSI) as a response biomarker in standard clinical care of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide

Background: Enzalutamide (ENZ), an androgen receptor antagonist therapy, was approved for patients (pts) with mCRPC. However, in standard of care for mCRPC pts, change in prostate specific antigen (PSA) is not accepted as an efficacy response measurement and the radiological change is inadequately measured in an interpreter-dependent subjective analysis of bone scan. Therefore, an objective effica

Sub-micrometer morphology of human atherosclerotic plaque revealed by synchrotron radiation-based μCT—A comparison with histology

Histology is a long standing and well-established gold standard for pathological characterizations. In recent years however, synchrotron radiation-based micro-computed tomography (SRμCT) has become a tool for extending the imaging of two-dimensional thin sections into three-dimensional imaging of tissue blocks, enabling so-called virtual histology with arbitrary clipping planes, volumetric renderi

Side-group switching between metal-to-ligand charge-transfer and metal-centered excited state properties in iron(II) N-heterocyclic carbene complexes

Fe(II) N-heterocyclic carbene (NHC) complexes have emerged over the last decade as a promising class of light-harvesting complexes for a variety of photochemical applications relying on the presence of high-energy excited states of mainly charge-transfer character with excited state lifetimes of tens of picoseconds or longer. Recent spectroscopic investigations have significantly refined the under

Artificial nanophotonic neuron with internal memory for biologically inspired and reservoir network computing

Neurons with internal memory have been proposed for biological and bio-inspired neural networks, adding important functionality. We introduce an internal time-limited charge-based memory into a III-V nanowire (NW) based optoelectronic neural node circuit designed for handling optical signals in a neural network. The new circuit can receive inhibiting and exciting light signals, store them, perform

Tailoring the Photophysical Properties of a Homoleptic Iron(II) Tetra N-Heterocyclic Carbene Complex by Attaching an Imidazolium Group to the (CNC) Pincer Ligand─A Comparative Study

We here report the synthesis of the homoleptic iron(II) N-heterocyclic carbene (NHC) complex [Fe(miHpbmi)2](PF6)4 (miHpbmi = 4-((3-methyl-1H-imidazolium-1-yl)pyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)) and its electrochemical and photophysical properties. The introduction of the π-electron-withdrawing 3-methyl-1H-imidazol-3-ium-1-yl group into the NHC ligand framework resulted in stabilizat

Deep learning performance on MRI prostate gland segmentation : evaluation of two commercially available algorithms compared with an expert radiologist

PURPOSE: Accurate whole-gland prostate segmentation is crucial for successful ultrasound-MRI fusion biopsy, focal cancer treatment, and radiation therapy techniques. Commercially available artificial intelligence (AI) models, using deep learning algorithms (DLAs) for prostate gland segmentation, are rapidly increasing in numbers. Typically, their performance in a true clinical context is scarcely

Experimental exploration of potassium compounds in the vicinity of a burning biomass pellet : From near-surface to downstream

The concentrations of gas-phase potassium hydroxide (KOH), potassium chloride (KCl) and atomic potassium (K(g)) were quantitatively measured from the near-surface to downstream area of burning pinewood pellets by a newly developed photofragmentation tunable diode laser absorption spectroscopy (PF-TDLAS) technique to reveal the original form of the released potassium. The novel arrangement of the P

Ignition, stabilization and particle-particle collision in lifted aluminum particle cloud flames

Micron-sized aluminum (Al) particles have recently been proposed as promising carbon-free energy carriers. To facilitate the application of micron-sized Al particles as fuel in practical energy generation system, this study experimentally investigates the underlying mechanisms of the ignition, stabilization and particle-particle collision in lifted Al particle cloud flames. High-resolution shadowg

High Oestrogen receptor alpha expression correlates with adverse prognosis and promotes metastasis in colorectal cancer

In normal colon tissue, oestrogen receptor alpha (ERα) is expressed at low levels, while oestrogen receptor beta (ERβ) is considered the dominant subtype. However, in colon carcinomas, the ERα/β ratio is often increased, an observation that prompted us to further investigate ERα’s role in colorectal cancer (CRC). Here, we assessed ERα nuclear expression in 351 CRC patients. Among them, 119 exhibit

Genomic deletion of Bcl6 differentially affects conventional dendritic cell subsets and compromises Tfh/Tfr/Th17 cell responses

Conventional dendritic cells (cDC) play key roles in immune induction, but what drives their heterogeneity and functional specialization is still ill-defined. Here we show that cDC-specific deletion of the transcriptional repressor Bcl6 in mice alters the phenotype and transcriptome of cDC1 and cDC2, while their lineage identity is preserved. Bcl6-deficient cDC1 are diminished in the periphery but

Proteomic Analysis of Primary Graft Dysfunction in Porcine Lung Transplantation Reveals Alveolar-Capillary Barrier Changes Underlying the High Particle Flow Rate in Exhaled Breath

Primary graft dysfunction (PGD) remains a challenge for lung transplantation (LTx) recipients as a leading cause of poor early outcomes. New methods are needed for more detailed monitoring and understanding of the pathophysiology of PGD. The measurement of particle flow rate (PFR) in exhaled breath is a novel tool to monitor and understand the disease at the proteomic level. In total, 22 recipient

Prevalence and classification of meniscal calcifications in the human knee

OBJECTIVE: To investigate the occurrence of meniscal calcifications in individuals with and without knee osteoarthritis (OA). Additionally, we aim to identify the specific types of calcifications: basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP).METHOD: We analysed 82 meniscal posterior horn samples (medial and lateral) collected from 41 human subjects. Among them, 20 indivi

Multifaceted Deactivation Dynamics of Fe(II) N-Heterocyclic Carbene Photosensitizers

Excited state dynamics of three iron(II) carbene complexes that serve as prototype Earth-abundant photosensitizers were investigated by ultrafast optical spectroscopy. Significant differences in the dynamics between the investigated complexes down to femtosecond time scales are used to characterize fundamental differences in the depopulation of triplet metal-to-ligand charge-transfer (3MLCT) excit

Bismuth-oxide nanoparticles: study in a beam and as deposited

Bi2O3 is a promising material for solid-oxide fuel cells (SOFC) due to the high ionic conductivity of some phases. The largest value is reached for its δ-phase, but it is normally stable at temperatures too high for SOFC operation, while nanostructured oxide is believed to have more suitable stabilization temperature. However, to manufacture such a material with a controlled chemical composition i

Swedish musculoskeletal researchers view on a collaborative network and future research priorities in Swedish healthcare

Background: Musculoskeletal disorders (MSK) are a global burden causing significant suffering and economic impact. Systematic identification and targeting of research questions of highest interest for stakeholders can aid in improving MSK disorder knowledge and management. Objective: To obtain Swedish MSK researchers' opinions and views on a collaborative Swedish MSK network (SweMSK) and identify