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Cell-Free DNA Promotes Thrombin Autolysis and Generation of Thrombin-Derived C-Terminal Fragments

Cell-free DNA (cfDNA) is the major structural component of neutrophil extracellular traps (NETs), an innate immune response to infection. Antimicrobial proteins and peptides bound to cfDNA play a critical role in the bactericidal property of NETs. Recent studies have shown that NETs have procoagulant activity, wherein cfDNA triggers thrombin generation through activation of the intrinsic pathway o

Chemokines modulate glycan binding and the immunoregulatory activity of galectins

Galectins are versatile glycan-binding proteins involved in immunomodulation. Evidence suggests that galectins can control the immunoregulatory function of cytokines and chemokines through direct binding. Here, we report on an inverse mechanism in which chemokines control the immunomodulatory functions of galectins. We show the existence of several specific galectin-chemokine binding pairs, includ

Drug-Coated Balloons Versus Drug-Eluting Stents or Plain Old Balloon Angioplasty : A Long-Term in-Stent Restenosis Study

BACKGROUND: Balloon angioplasty with drug-coated balloons (DCBs) is frequently used during percutaneous coronary intervention for in-stent restenosis. Despite its frequent use, there is a lack of long-term data on the efficacy of DCB angioplasty. We conducted an investigation on the long-term efficacy outcome of in-stent restenosis, comparing DCBs, drug-eluting stents, and plain old balloon angiop

Ibuprofen for acute postoperative pain in children

BACKGROUND: Children often require pain management following surgery to avoid suffering. Effective pain management has consequences for healing time and quality of life. Ibuprofen, a frequently used non-steroidal anti-inflammatory drug (NSAID) administered to children, is used to treat pain and inflammation in the postoperative period.OBJECTIVES: 1) To assess the efficacy and safety of ibuprofen (

Enzyme Architecture : Modeling the Operation of a Hydrophobic Clamp in Catalysis by Triosephosphate Isomerase

Triosephosphate isomerase (TIM) is a proficient catalyst of the reversible isomerization of dihydroxyacetone phosphate (DHAP) to d-glyceraldehyde phosphate (GAP), via general base catalysis by E165. Historically, this enzyme has been an extremely important model system for understanding the fundamentals of biological catalysis. TIM is activated through an energetically demanding conformational cha

Discovery and Optimization of the First Highly Effective and Orally Available Galectin-3 Inhibitors for Treatment of Fibrotic Disease

Galectin-3 is a carbohydrate-binding protein central to regulating mechanisms of diseases such as fibrosis, cancer, metabolic, inflammatory, and heart disease. We recently found a high affinity (nM) thiodigalactoside GB0139 which currently is in clinical development (PhIIb) as an inhaled treatment of idiopathic pulmonary fibrosis. To enable treatment of systemically galectin-3 driven disease, we h

The Hidden Side of Complement Regulator C4BP : Dissection and Evaluation of Its Immunomodulatory Activity

C4b-binding protein (C4BP) is a well-known regulator of the complement system that holds additional and important activities unrelated to complement inhibition. Recently, we have described a novel immunomodulatory activity in the minor C4BP(β-) isoform directly acting over inflammatory phagocytes. Here we show that incorporation of the β-chain to the C4BP α-chain oligomer interferes with this immu

Solar and geomagnetic activity reduces pulmonary function and enhances particulate pollution effects

Background: Increased solar and geomagnetic activity (SGA) may alter sympathetic nervous system activity, reduce antioxidant activity, and modulate physiochemical processes that contribute to atmospheric aerosols, all which may reduce pulmonary function. Objectives: Investigate associations between forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC) with SGA, and assess whether

Conceptual Design of a Mid-Sized Semi-Closed Oxy-Fuel Combustion Combined Cycle

This paper presents the study of a mid-sized semi-closed oxy-fuel combustion combined cycle (SCOC-CC) with net power output around 108 MW. The paper describes not only the power balance and the performance of the SCOC-CC, but also the conceptual design of the SCOC turbine and compressor. A model has been built in the commercial heat and mass balance code IPSEpro to estimate the efficiency of semi-

Cosmology from Strong Interactions

A wealth of theoretical and phenomenological information about Quantum Chromodynamics at short and long distances collected so far in major collider measurements has profound implications in cosmology. In this review, we give a brief discussion of major implications of strongly-coupled dynamics of quarks and gluons and effects of their collective motion in physics of early Universe and in astrophy

A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee

BACKGROUND: Many clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of clinical thrombotic events. Aspirin and ticlopidine have been shown to be effective, but both have potentially serious adverse effects. Clopidogrel, a new thienopyridine derivative similar to ticlopidine, is an inhibitor of platelet aggregation induced by adenosine diphosphate

EU sustainability criteria for biofuels potentially restrict ley crop production on marginal land for use as biogas substrate

Ley crops can be grown to provide a substrate for biogas vehicle-fuel production on a range of soils including marginal land. According to EU regulations, such biofuel currently has to achieve an emission reduction of 35%, but tightened goals of 50 and 60% will come into effect as early as 2017. In two field trials (one on marginal soil, one on productive soil) ley crop mixtures were tested and th

Is there a change in myocardial nonlinearity during the cardiac cycle?

The distortion of a sound wave during propagation results in progressive transfer of the energy from fundamental to higher harmonics, and is dependent on the nonlinearity of the medium. We studied if relative changes in acoustical nonlinearity occur in healthy myocardium during the cardiac cycle. Radiofrequency data were acquired from transthoracic echocardiography (2.5 and 3.5 MHz), parasternal l

Association between ecg abnormalities and fatal cardiovascular disease among patients with and without severe mental illness

BACKGROUND: ECG abnormalities are associated with adverse outcomes in the general population, but their prognostic significance in severe mental illness (SMI) remains unexplored. We investigated associations between no, minor, and major ECG abnormalities and fatal cardiovascular disease (CVD) among patients with SMI compared with controls without mental illness. METHODS AND RESULTS: We cross-linke

Social infrastructuring in public libraries : librarians’ continuous care in everyday library practice

Purpose: As social infrastructures, public libraries are increasingly recognised as providing more than access to books and information; librarians’ work is importantly centred around practices of care. However, the ways in which they provide care is poorly researched, let alone conceptualised. This paper explores how this important part of librarians’ daily work is practiced through the lens of i

Association of pesticide exposure with respiratory health outcomes and rhinitis in avocado farmworkers from Michoacán, Mexico

Background: A growing literature suggests associations between occupational pesticide exposure and respiratory health. In this study, we aimed to examine the association of exposure to insecticides, fungicides, and herbicides, individually and as a mixture, with respiratory health outcomes and rhinitis in avocado farmworkers from Michoacán, Mexico. Material and methods: We conducted a cross-sectio

Structural basis of Cfr-mediated antimicrobial resistance and mechanisms for its evasion

The ribosome is an essential drug target as many classes of clinically important antibiotics bind and inhibit its functional centers. The catalytic peptidyl transferase center (PTC) is targeted by the broadest array of inhibitors belonging to several chemical classes. One of the most abundant and clinically prevalent mechanisms of resistance to PTC-acting drugs is C8-methylation of the universally

Tips for creating inclusive classrooms at LTH

All people are different. All teachers are different. All students are different. They have different life situations, different study situations, and different preferences, conditions, and abilities. How can we take this diversity into account when we plan our teaching and exams? What situations should we prepare for? How can we help students focus on their learning and not on unnecessary obstacl