Miracle-dz/UniFAR-FTUs huggingface dataset:
Isoflurane promotes phagocytosis of apoptotic neutrophils through AMPK-mediated ADAM17/Mer signaling

A patient’s recovery from lung inflammatory injury or development of multi-system organ failure is determined by the host’s ability to resolve inflammation and repair tissue damage, both of which require the clearance of apoptotic neutrophils by macrophages (efferocytosis). Here, we investigated the effects of isoflurane on macrophage efferocytosis and resolution of lung inflammatory injury. Treatment of murine bone marrow-derived macrophages (BMDMs) or alveolar macrophages with isoflurane dramatically enhanced phagocytosis of apoptotic neutrophils. Isoflurane significantly increased the surface expression of the receptor tyrosine kinase Mer in macrophages, but markedly decreased the levels of a soluble form of Mer protein in the medium. Isoflurane treatment also caused a decrease in a disintegrin and metalloproteinase 17 (ADAM17) on the cell surface and a concomitant increase in its cytoplasmic fraction. These responses induced by isoflurane were completely reversed by a pharmacological inhibitor or genetic deletion of AMP-activated protein kinase (AMPK). In a mouse model of lipopolysaccharide-induced lung injury, isoflurane accelerated the recovery of lung inflammation and injury that was coupled with an increase in the number of alveolar macrophages containing apoptotic bodies. In alveolar macrophage-depleted mice, administration of isoflurane-pretreated BMDMs facilitated resolution of lung inflammation following lipopolysaccharide challenge. Thus, isoflurane promoted resolution of lipopolysaccharide-induced lung inflammatory injury via enhancement of macrophage efferocytosis. Increased macrophage efferocytosis following isoflurane treatment correlates with upregulation of Mer surface expression through AMPK-mediated blockade of ADAM17 trafficking to the cell membrane.
Biodegradable and renewable poly(lactide)–lignin composites: synthesis, interface and toughening mechanism

Poly(lactide) (PLA)–lignin composites were fabricated by blending lignin-g-rubber-g-poly(D-lactide) copolymer particles and commercial poly(L-lactide) (PLLA) in chloroform. To synthesize the copolymer, a poly(e-caprolactone-co-lactide) (PCLLA) rubbery layer was formed via the lignin-initiated ring opening copolymerization of an e-caprolactone/L-lactide mixture, followed by the formation of poly(D-lactide) (PDLA) outer segments via the polymerization of D-lactide. The PDLA segments may contribute to strong interfacial interactions between lignin-rubber-PDLA and PLLA matrix by stereocomplexation, which was observed using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and wide angle X-ray scattering (WAXS). The quasi-random structure of PCLLA and the formation of the outer PDLA segments were characterized by nuclear magnetic resonance (NMR). A Tg of ∼−36 °C for PCLLA was detected by DSC, which confirms the rubbery character of the synthesized copolymer. The resulting renewable and biodegradable composites exhibited a six-fold increase of elongation at break and a simultaneous improvement in their tensile strength and Young's modulus, though to a lesser extent. Light scattering, WAXS, small angle X-ray scattering (SAXS) and scanning electron microscope (SEM) studies suggested that good lignin dispersion, rubber-initiated crazing and strong filler/matrix interactions due to stereocomplexation are the effective mechanisms behind the excellent mechanical performance of these composites.
Developing a Non-Pharmacological Intervention for Individuals With Mild Cognitive Impairment

The purpose of this study is to describe one potential intervention model that is designed to slow decline to disability for individuals at-risk for dementia due to Mild Cognitive Impairment. Strategy training is a treatment model that focuses on behavioral activation through addressing barriers to daily activities. Strategy training encourages development of goals and plans to address self-identified impaired processes, and it maintains or improves individuals’ ability to perform desired activities. Progression to dementia may be slowed due to the link between engagement in daily activities and production of biological factors associated with neurocognitive health. We demonstrated that an older adult with mild cognitive impairment is able to develop goals, establish effective plans, and engage in daily activities through the strategy training intervention model.
Supramolecular aggregates in high magnetic fields

Creating new well-defined structures with a nanometer or micrometer length scale is of great importance, which can lead to new devices, new materials, and allows the study of fundamental physical phenomena. A promising approach for creating such structures is the use of organic molecules that spontaneously form higher dimensional structures in solution. With this process, extremely small self-repairing structures can be created in a relatively cheap and easily processable way. Almost any shape and size is possible, ranging from large spherical aggregates with a diameter in the micrometer range, to small wires of only a few nanometers thin. There are many applications, for example in the transport of light through narrow channels, as miniature gas sensors or as small capsules in drug delivery systems. In this thesis, we use magnetic fields to improve our understanding of the formation of supramolecular self-assemblies. Due to the anisotropic magnetic properties of the molecules, a supramolecular aggregate can be oriented in a magnetic field. The way it aligns, parallel or perpendicular to the magnetic field, and the field strength required for the alignment, depends on the size, degree of order, and the intermolecular organization of the aggregate. We investigate the relation between environmental aspects (like temperature and solvent) and the shape and internal structure of the resulting aggregates, we influence the shape with a magnetic field, we compare the growth process with theoretical models and we describe the kinetics of an aggregate system. Understanding these aspects leads to a better understanding of the formation process, which will allow us to build aggregates with the desired size, shape and functionality.
The 'obesity paradox' in atrial fibrillation: observations from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial.

AIMS The prognostic implication of adiposity on clinical outcomes in atrial fibrillation (AF) patients treated with oral anticoagulation is unclear. METHODS AND RESULTS A total of 17 913 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial had body mass index (BMI) measured at baseline. For the primary analysis, BMI was categorized as normal (18.5 to <25 kg/m2), overweight (25 to <30 kg/m2), and obese (≥30 kg/m2). Waist circumference (WC) was defined as high if >102 cm for men and >88 cm in women. Outcomes were stroke or systemic embolism, a composite endpoint (stroke, systemic embolism, myocardial infarction, or all-cause mortality), all-cause mortality, and major bleeding. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) across categories of BMI and WC adjusting for established risk factors and treatment allocation. At baseline, 4052 (22.6%) patients had a normal BMI, 6702 (37.4%) were overweight, and 7159 (40.0%) were obese. In multivariable analyses, higher BMI was associated with a lower risk of all-cause mortality [overweight: HR 0.67 (95% CI 0.59-0.78); obese: HR 0.63 (95% CI 0.54-0.74), P < 0.0001] and the composite endpoint [overweight: HR 0.74 (95% CI 0.65-0.84); obese: HR 0.68 (95% CI 0.60-0.78), P < 0.0001] compared with normal BMI. In women, high WC was associated with a 31% lower risk of all-cause mortality (P = 0.001), 27% lower risk of the composite endpoint (P = 0.001), and 28% lower risk of stroke or systemic embolism (P = 0.048) but not in men. There was no significant association between adiposity and major bleeding. CONCLUSION In patients with AF treated with oral anticoagulants, higher BMI and WC are associated with a more favourable prognosis.
Distribution and quantitative analysis of CIDEa and CIDEc in broiler chickens: accounting for differential fat deposition between strains

ABSTRACT 1. Differences in the expression of CIDEa and CIDEc in 20 different tissues were examined. Both CIDEa and CIDEc mRNA transcripts were predominantly but variably expressed in white adipose tissue (WAT) but were also expressed at moderate levels in the kidney and liver and at lower levels in the ovary. Interestingly, among WAT types, both CIDEa and CIDEc were expressed at the lowest levels in heart coronary WAT. 2. To better understand the roles of CIDEa and CIDEc in the fat deposition of broiler chickens, the differences in lipid droplet (LD) size and mRNA levels of CIDEa and CIDEc between lean-type and fat-type broiler chicken lines were studied. LD sizes were larger in fat-type broiler lines, and CIDEa and CIDEc mRNA levels in white adipose, kidney and liver tissues were significantly higher in fat-type broiler lines than in their lean counterparts. 3. Developmental expression patterns of CIDEa and CIDEc mRNA were analysed in different tissue types (WAT, liver and kidney) in Arbor Acres broiler chickens, and CIDEa and CIDEc mRNA expression levels increased during sequential developmental stages, achieving peak expression levels at week 6. 4. These observations suggest that the functions of CIDEa and CIDEc reflect inherent characteristics of lipid metabolism that contribute to the differences in fat deposition between strains. The results in this study contribute to a more robust understanding of the tissue distribution and expression patterns of CIDEa and CIDEc mRNA and facilitate further research concerning the molecular mechanism underlying fat deposition in broiler chickens.
3D Pose Regression Using Convolutional Neural Networks

3D pose estimation is a key component of many important computer vision tasks such as autonomous navigation and 3D scene understanding. Most state-of-the-art approaches to 3D pose estimation solve this problem as a pose-classification problem in which the pose space is discretized into bins and a CNN classifier is used to predict a pose bin. We argue that the 3D pose space is continuous and propose to solve the pose estimation problem in a CNN regression framework with a suitable representation, data augmentation and loss function that captures the geometry of the pose space. Experiments on PASCAL3D+ show that the proposed 3D pose regression approach achieves competitive performance compared to the state-of-the-art.
Identification of Peptidoglycan Hydrolase Constructs with Synergistic Staphylolytic Activity in Cow's Milk

ABSTRACT Peptidoglycan hydrolases (PGHs) have been suggested as novel therapeutics for the treatment of bovine mastitis. However, activity in the presence of cow's milk is an important requirement for drugs administered into the bovine udder. We have screened a library of >170 recombinant PGHs, including engineered bacteriophage endolysins, for enzymes with activity against Staphylococcus aureus in milk, using a microtiter plate-based protocol. Nine suitable PGH constructs were identified by this approach and further compared in time-kill assays for their efficacy against S. aureus in heat-treated milk. The three most active enzymes (lysostaphin, Ami2638A, and CHAPK_CWT-LST) reduced S. aureus in milk to undetectable numbers within minutes at nanomolar concentrations. Due to their different peptidoglycan cleavage sites, these PGH constructs revealed synergistic activity in most combinations, as demonstrated by checkerboard assays, spot assays, and time-kill experiments. Furthermore, they proved active against a selection of staphylococcal mastitis isolates from different geographical regions when applied individually or in synergistic combination. The most effective PGH combination completely eradicated S. aureus from milk, with no more bacteria being detected within 24 h after addition of the enzymes, corresponding to a reduction of >9 log units compared to the control. Efficacy was also retained at different inoculum levels (3 versus 6 log CFU/ml) and when S. aureus was grown in milk as opposed to broth prior to the experiments. In raw cow's milk, CHAPK_CWT-LST showed reduced efficacy, whereas both Ami2638A and lysostaphin retained their activity, reducing bacterial numbers by >3.5 log units within 3 h. IMPORTANCE Staphylococci and S. aureus in particular are a major cause of bovine mastitis, an inflammation of the mammary gland in cows associated with high costs and risks for consumers of milk products. S. aureus-induced mastitis, commonly treated by intramammary infusion of antibiotics, is characterized by low cure rates and increasing antibiotic resistance in bacteria. Therefore, alternative treatment options are highly desirable. PGHs, including bacteriophage endolysins, rapidly and specifically kill selected pathogens by degrading their cell wall and are refractory to resistance development, therefore holding promise as novel antibacterial agents. This study employed a screening approach to identify PGH constructs with high staphylolytic activity in cow's milk within a large collection of enzymes. Our results suggest that the most promising enzymes identified by this strategy hold potential as novel mastitis therapeutics and support their further characterization in animal models.
Study on the Effect of Aging on the Ability of Calcium Carbide for Hot Metal Desulfurization

Industrial trials and laboratory study are carried out to investigate the effect of aging on the ability of CaC2 in hot metal desulfurization. The industrial trials indicate that the time of storage of calcium carbide within the limit of industrial practice has no appreciable effect on its ability of desulfurization. In the laboratory, samples of CaC2 are prepared by exposing them in air for different times to promote formation of a Ca(OH)2 outer layer. The thickness of Ca(OH)2 increases with exposing time. Thereafter, the aged CaC2 samples are employed for desulfurization at 1673 and 1773 K for 8 min. For all the samples after desulfurization, layers of graphite and CaO are found between the remaining CaC2 particles and the outer CaS layer. The desulfurization using CaC2 is found to proceed by the diffusion of calcium vapor through the product layers and then its reaction with dissolved sulfur in the hot metal at the surface. No appreciable difference in the thickness of the CaS layer is found with the samples exposed to air for different times. This finding explains well the industrial results.
Rheological and Morphological Properties of Immiscible Blends and Microfiber Preparation from the Blends

Abstract One modified poly(ethylene terephthalate) (m-PET) containing 16 mol% of isophthalic acid content and three kinds of isotactic polypropylene (i-PP) with different molecular weights were melt blended in various volume ratios by a twin screw extruder. The dynamic viscosity of the i-PP/m-PET blend showed positive deviation at lower volume content of i-PP and negative deviation at higher volume content of i-PP. The size of dispersed phase increased with an increase of the minor component. Also, the less difference between the viscosities of two polymers caused the smaller particle size in the blend and the smaller critical Weber number. After melt spinning of these binary polymer blends, m-PET and i-PP micro staple fiber, whose diameter was about 0.13 to 2.75 μm, could be obtained by extracting the continuous phase with a proper solvent. The less the minor component in the blend, the better the spinnability of the blended polymers and the physical properties of the fiber. Also, when i-PP was the continuous phase, the spinnability and the physical properties of the fibers were better than the opposite case. Molecular weight of i-PP and the blend ratio had a marked influence on the diameter of microfibers. The micro fiber obtained from i-PP which has similar viscosity with m-PET showed the smallest diameter than those obtained from other two i-PPs.
Modelling of Steel Fibre Reinforced Concrete Ribbed Slab under Multiple Ribbed Condition

Nowadays, demands in the application of fiber in concrete increase gradually as an engineering material. Rapid cost increment of material causes the increase in demand of new technology that provides safe, efficient and economical design for the present and future application. The introduction of ribbed slab reduces the material and thus the cost but the strength of the structure also reduce due to the reducing material. This paper will focus on modelling behavior of ribbed slab reinforced with steel fibre using Lusas Modeller. The structure design is in full aspect to optimize the function of steel fibre and the slab rib capability. This research focus on modelling of multiple type of steel fibre ribbed slab consist of two ribbed slab, and also three ribbed slab in similar size of 1500mm x 1000mm x 75mm using concrete Grade 30. Load was applied until failure under three point loading system. It is importance to find the ultimate strength of the sample and the behavior of structure under vertical stress. Steel fibre is expected to reduce the issue of micro crack and enhance the performance of concrete.
Mutation-Enrichment Next-Generation Sequencing for Quantitative Detection of KRAS Mutations in Urine Cell-Free DNA from Patients with Advanced Cancers

Purpose: Tumor-derived cell-free DNA (cfDNA) from urine of patients with cancer offers noninvasive biological material for detection of cancer-related molecular abnormalities such as mutations in Exon 2 of KRAS. Experimental Design: A quantitative, mutation-enrichment next-generation sequencing test for detecting KRASG12/G13 mutations in urine cfDNA was developed, and results were compared with clinical testing of archival tumor tissue and plasma cfDNA from patients with advanced cancer. Results: With 90 to 110 mL of urine, the KRASG12/G13 cfDNA test had an analytical sensitivity of 0.002% to 0.006% mutant copies in wild-type background. In 71 patients, the concordance between urine cfDNA and tumor was 73% (sensitivity, 63%; specificity, 96%) for all patients and 89% (sensitivity, 80%; specificity, 100%) for patients with urine samples of 90 to 110 mL. Patients had significantly fewer KRASG12/G13 copies in urine cfDNA during systemic therapy than at baseline or disease progression (P = 0.002). Compared with no changes or increases in urine cfDNA KRASG12/G13 copies during therapy, decreases in these measures were associated with longer median time to treatment failure (P = 0.03). Conclusions: A quantitative, mutation-enrichment next-generation sequencing test for detecting KRASG12/G13 mutations in urine cfDNA had good concordance with testing of archival tumor tissue. Changes in mutated urine cfDNA were associated with time to treatment failure. Clin Cancer Res; 23(14); 3657–66. ©2017 AACR.
Deficiency of a sulfotransferase for sialic acid-modified glycans mitigates Alzheimer’s pathology

Significance Keratan sulfate (KS) is an extracellular sulfated glycan covalently attached to core proteins in the brain. Here, we show that a type of KS with a certain molecular mass in microglia and its synthetic enzyme GlcNAc6ST1, previously known as a sulfotransferase for ligands of L-selectin, are upregulated in model mice and patients with Alzheimer’s disease. GlcNAc6ST1 deficiency resulted in increased amyloid-β phagocytosis and hyperresponsiveness to an antiinflammatory cytokine in primary microglia. Moreover, amyloid-β pathology was mitigated in GlcNAc6ST1-deficient Alzheimer’s model mice. These data support a model in which GlcNAc6ST1 regulates microglial functions via synthesizing sialic acid-modified KS, a potential ligand for microglial carbohydrate-recognizing receptors, in Alzheimer’s pathology. We previously showed that microglial keratan sulfate (KS) was induced in amyotrophic lateral sclerosis. However, the functional roles of the glycan and its synthetic enzyme in neurodegenerative diseases, such as Alzheimer’s disease (AD), a progressive disorder, are unclear. In our study, KS modified with sialic acids having a molecular mass of 125–220 kDa and the carbohydrate sulfotransferase GlcNAc6ST1 were up-regulated in the brains of two transgenic mouse models (J20 and Tg2576) and the brains of patients with AD. GlcNAc6ST1-deficient J20 (J20/GlcNAc6ST1−/−) mice demonstrated a complete absence of the microglial sialylated KS. J20/GlcNAc6ST1−/− primary microglia showed an increased level of amyloid-β phagocytosis and were hyperresponsive to interleukin 4, a potent antiinflammatory cytokine. Moreover, J20/GlcNAc6ST1−/− mice manifested reduced cerebral amyloid-β deposition. GlcNAc6ST1-synthesizing sialylated KS thus modulates AD pathology. Inhibition of KS synthesis by targeting GlcNAc6ST1 may therefore be beneficial for controlling AD pathogenesis.
Plasma interleukin-6 levels, glutathione peroxidase and isoprostane in obese women before and after weight loss. Association with cardiovascular risk factors.

OBJECTIVE To evaluate the levels of Interleukin-6 (IL-6), glutathione peroxidase and isoprostane in obese women and their association with markers of cardiovascular risk factors before and after weight loss. DESIGN 36 healthy obese women of reproductive age (group A: age (mean+/-SD) 35.4+/-9.2 years, Body Mass Index (BMI) 38.5+/-7 kg/m2) and 30 healthy, normal weight women (group B: age mean+/-SD 34.9+/-7.4 y., BMI 24+/-1.1 kg/m2) were included in the study. Glucose tolerance was normal in all participating women. Il-6, glutathione peroxidase and isoprostane, C-Reactive Protein (CRP), insulin, fasting plasma glucose, HOMA-IR as well as the lipid profile were evaluated. Body weight, BMI, Waist to Hip ratio (W/H) ratio, Waist Circumference (WC), %free fat mass and the %fat mass were also measured. A hypo-caloric diet was prescribed for the obese women and all participants were re-examined after six months. RESULTS In obese women after weight loss, anthropometric obesity markers (BMI, W/H ratio), %fat, lipid profile, insulin levels and inflammation indices such as IL-6 and CRP, the oxidative stress index isoprostane, as well as glutathione peroxidase were significantly ameliorated. The levels of serum glutathione peroxidase activity were negatively correlated with IL-6 levels and were significantly increased after weight reduction. In obese women there was an association between IL-6 levels and the values of %fat, %free fat mass, insulin and HOMA-IR before and after weight loss. CONCLUSIONS Weight loss is related to reduction of oxidative stress and inflammation; this beneficial effect could possibly be translated into reduction of cardiovascular risk in obese individuals.