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Real-time structural characterization of protein response to a caged compound by fast detector readout and high-brilliance synchrotron radiation

Protein dynamics are essential to biological function, and methods to determine such structural rearrangements constitute a frontier in structural biology. Synchrotron radiation can track real-time protein dynamics, but accessibility to dedicated high-flux single X-ray pulse time-resolved beamlines is scarce and protein targets amendable to such characterization are limited. These limitations can

Effect of arthroscopic partial meniscectomy on structural degeneration of the knee – A 5-year MRI-based follow-up of the placebo-surgery controlled FIDELITY (Finnish Degenerative Meniscus Lesion Study) trial

Objective: To assess the 5-year effects of arthroscopic partial meniscectomy (APM) vs. placebo surgery on the development of the structural changes of the knee by magnetic resonance imaging (MRI). Design: This multicentre, randomized, participant- and outcome-assessor-blinded, placebo-surgery-controlled trial was carried out in Finland. We randomized 146 adults, mean age 52 years (range 35 to 65)

Investigating the Local Bonding Structure of Amorphous Zinc Tin Oxide to Elucidate the Effect of Altering the Intercation Ratio

In this paper, the local bonding structure in amorphous zinc tin oxide (a-ZTO) is probed using a combination of XANES and EXAFS techniques at the Zn and Sn K-edges to gain insight into charge carrier generation in the material. a-ZTO is prepared using two growth methods; spray pyrolysis and magnetron sputtering. It is seen that a-ZTO grown by magnetron sputtering shows no changes in the chemical e

Remote Sensing-Based Assessment of Dry-Season Forage Quality for Improved Rangeland Management in Sahelian Ecosystems

Residents of the Sahel depend on livestock, but harsh environmental conditions during the dry season limit rangeland forage, which is the main source of livestock feed. Al-though operational tools exist for assessing and monitoring forage quantity during the dry season, assessments of forage quality are lacking. We addressed this gap by developing satellite-based monitoring of forage quality acros

Risk of COVID-19 hospitalisation by HIV-status and SARS-CoV-2 vaccination status during pre- and post-Omicron era in a national register-based cohort study in Sweden

Background: Data on the outcomes of COVID-19 in people living with HIV (PLHIV), specifically in relation to vaccination status, are lacking during the Omicron era. Methods: This nationwide registry-based study included all resident in Sweden ≥18 years with a positive SARS-CoV-2 PCR test during January 2021–February 2023. We estimated adjusted odds ratios (adjOR) for COVID-19 hospitalisation and se

The risk of hemochromatosis among first- and second-generation immigrants : a cohort study of the total population in Sweden

Purpose: We aimed to analyze the risk of hereditary hemochromatosis (HH) among first-generation and second-generation immigrants in Sweden using Swedish-born individuals and Swedish-born individuals with Swedish-born parents as referents, respectively. Methods: All individuals aged 18 years of age and older, n = 6,180,500 in the first-generation study, and n = 4,589,930 in the second-generation st

A Unifying Statement for an H-Infinity Optimal Controller with Positivity Properties

In this paper, we unify two already published results on state feedback H-infinity optimality. Previously, optimality has been shown for a particular controller structure in the case that the open-loop state matrix is symmetric, as well as in the case that the closed-loop system is internally positive. By contrast, the main result of the present paper gives optimality based on neither of these two

A Potent and Selective PARP11 Inhibitor Suggests Coupling between Cellular Localization and Catalytic Activity

Poly-ADP-ribose polymerases (PARPs1-16) play pivotal roles in diverse cellular processes. PARPs that catalyze poly-ADP-ribosylation (PARylation) are the best characterized PARP family members because of the availability of potent and selective inhibitors for these PARPs. There has been comparatively little success in developing selective small-molecule inhibitors of PARPs that catalyze mono-ADP-ri

Temporal Relationship Between Pain and Mental Health Conditions Among Children and Young People—A Population-Based Register Study in Sweden

Both pain and mental health conditions are common among young people. They often co-occur, but we wanted to investigate further whether it is pain (abdominal pain, headache, musculoskeletal pain, menstrual pain) that precedes mental health conditions (depression, anxiety, stress, phobia) or whether it is the other way around, mental health conditions that precede pain. Using electronic health reco

Percutaneous coronary intervention plus medical therapy versus medical therapy alone in chronic coronary syndrome : a propensity score-matched analysis from the Swedish Coronary Angiography and Angioplasty Registry

Background Percutaneous coronary intervention (PCI) is frequently used for patients with chronic coronary syndrome (CCS). However, the role of PCI beyond symptom relief in CCS remains controversial. The objective of this study was to determine whether PCI is associated with better outcomes, compared with medical therapy (MT) alone. Methods We conducted a retrospective cohort study. Using the Swedi

Clustering Methods for the Characterization of Synchrotron Radiation X-Ray Fluorescence Images of Human Carotid Atherosclerotic Plaque

This study employs computational algorithms to automatically identify and classify features in X-Ray fluorescence (XRF) microscopy images. Principal component analysis (PCA) and unsupervised machine learning algorithms, such as Gaussian mixture (GM) clustering, are implemented to label features on a collection of XRF maps of human atherosclerotic plaque samples. The investigation involves the hard

Psychological need satisfaction, frustration, and unfulfillment profiles in the workplace : Their nature, predictors, and outcomes

Based on self-determination theory, this research relied on person-centered analyses to show how the distinct components of psychological need states combine to produce distinct profiles. We also explored contemporarily antecedents (perceptions of the organization's environmental corporate social responsibility and negative moral emotions related to the organization's environmental (ir)responsibil

A DNA-Encoded Library of Chemical Compounds Based on Common Scaffolding Structures Reveals the Impact of Ligand Geometry on Protein Recognition

A DNA-encoded chemical library (DECL) with 1.2 million compounds was synthesized by combinatorial reaction of seven central scaffolds with two sets of 343×492 building blocks. Library screening by affinity capture revealed that for some target proteins, the chemical nature of building blocks dominated the selection results, whereas for other proteins, the central scaffold also crucially contribute

Design, synthesis and evaluation of potent and selective inhibitors of mono-(ADP-ribosyl)transferases PARP10 and PARP14

A series of diaryl ethers were designed and synthesized to discern the structure activity relationships against the two closely related mono-(ADP-ribosyl)transferases PARP10 and PARP14. Structure activity studies identified 8b as a sub-micromolar inhibitor of PARP10 with ∼15-fold selectivity over PARP14. In addition, 8k and 8m were discovered to have sub-micromolar potency against PARP14 and demon

High concordance of PET-CT treatment response evaluation according to PERCIST 1.0 when comparing images reconstructed with OSEM vs. BSREM

Background: Positron emission tomography (PET) response criteria in solid tumours (PERCIST 1.0) is a systematic assessment of therapy response with fluorine 18 fluorodeoxyglucose ([18F]FDG) PET. The ordered subset expectation maximization (OSEM) and block sequential regularized expectation maximization (BSREM) reconstruction algorithms are both commonly used. The impact of using OSEM or BSREM on P

Two intuitions about free will—Some afterthoughts

In 2014, Christian List and I published a paper that delineated our view regarding what it takes for an agent to act freely. We suggested that this requires the action to be endorsed by the agent and caused by this endorsement and yet not be necessitated. Free action requires indeterminism at the agential level—the kind of indeterminism that is compatible with physical determinism. I still think t

How to evaluate exertional breathlessness using normative reference equations in research

Purpose of review Breathlessness is a common, distressing and limiting symptom in people with advanced disease, but is challenging to assess as the symptom intensity depends on the level of exertion (symptom stimulus) during the assessment. This review outlines how to use recently developed normative reference equations to evaluate breathlessness responses, accounting for level of exertion, for va

Identification of Poly(ADP-Ribose) Polymerase Macrodomain Inhibitors Using an AlphaScreen Protocol

Macrodomains recognize intracellular adenosine diphosphate (ADP)-ribosylation resulting in either removal of the modification or a protein interaction event. Research into compounds that modulate macrodomain functions could make important contributions. We investigated the interactions of all seven individual macrodomains of the human poly(ADP-ribose) polymerase (PARP) family members PARP9, PARP14

Structure-activity relationships for inhibitors of Pseudomonas aeruginosa exoenzyme S ADP-ribosyltransferase activity

During infection, the Gram-negative opportunistic pathogen Pseudomonas aeruginosa employs its type III secretion system to translocate the toxin exoenzyme S (ExoS) into the eukaryotic host cell cytoplasm. ExoS is an essential in vivo virulence factor that enables P. aeruginosa to avoid phagocytosis and eventually kill the host cell. ExoS elicits its pathogenicity mainly via ADP-ribosyltransferase