Miracle-dz/UniFAR-FTUs huggingface dataset:
Free fatty acids trigger apoptosis and inhibit cell cycle progression in human vascular endothelial cells

Plasma free fatty acid (FFA) concentrations are increased in states of insulin resistance and impair endothelial function. Because the underlying mechanisms are largely unknown, we examined selected, purified FFAs' (100–300 µmol/l, 24–48 h) action on apoptosis, cell cycle distribution, and associated gene/protein expression in human umbilical vein endothelial cells (HUVECs). Stearic acid, but not oleic acid, time and concentration dependently increased endothelial apoptosis by fivefold (n=6, P<0.01), whereas polyunsaturated FFAs (PUFAs; linoleic, γ‐linolenic, and arachidonic acid) exerted proapoptotic activity only at 300 µmol/l (P<0.05). Proapoptotic FFA action increased with FFAs' number of double bonds and with protein expression of the apoptosis promotor bak. The G0/G1 cell cycle arrest (n=6, P<0.05) induced by stearic acid (+14%) and PUFAs (+30%) is reflected by up‐regulation of p21WAF‐1/Cip1. In addition, all FFAs concentration dependently reduced (P<0.05) gene/protein expression of clusterin (–54%), NF‐κB's inhibitor, IκBα (–50%), endothelin‐1 (–44%), and endothelial NO synthase (–44%). Plasma samples obtained from individuals with elevated plasma FFAs (372±22 µmol/l) increased endothelial apoptosis by 4.2‐fold (P<0.001, n=10) compared with intraindividually matched low plasma FFA (56±21 µmol/l) conditions, underlining the results obtained by defined FFA stimulation. In conclusion, FFA structure differently affects endothelial cell proliferation and apoptosis, both representing key factors in the development of micro‐ and macrovascular dysfunction.
Access to the Published Version May Require Journal Subscription. Published with Permission From: Springer Memory in Relation to Depth of Sedation in Adult Mechanically Ventilated Intensive Care Patients

"Memory in relation to depth of sedation in adult mechanically ventilated intensive care patients" Abstract Objective: To investigate the relationship between memory and intensive care sedation. Design and setting: Prospective cohort study over 18 months in two general intensive care units (ICUs) in district university hospitals. Patients: 313 intubated mechanically ventilated adults admitted for more than 24 hours, 250 of whom completed the study. Measurements: Patients (n=250) were interviewed at ward 5 days after discharge from the ICU with support of the ICU Memory Tool. Patient characteristics, doses of sedative and analgesic agents, and sedation scores as measured by the Motor Activity Assessment Scale (MAAS) were collected from hospital records after the interview. Results: Patients with no recall (18%) were significantly older, had higher baseline severity of illness, and fewer periods of wakefulness (median proportion of MAAS score 3; 0.37 vs 0.70, p<0.0001), than those who had memories of the ICU (82%). Multivariate analyses showed that increasing proportion of MAAS 0-2 and older age were significantly associated with having no recall. Patients with delusional memories (34%) had significantly longer ICU stay (md 6.6 vs 2,2 days, p<0.0001), higher baseline severity of illness, higher proportions of MAAS scores 4-6 and more administration of midazolam, than those with recall of the ICU without delusional memories. Conclusions: This study suggests that heavy sedation increases the risk of having no recall, and longer ICU stay increases the risk of delusional memories. The depth of sedation during total ICU as recorded with the MAAS may predict the probability of having memories of the ICU.
Brain white matter lesions detected by magnetic resosnance imaging are associated with balance and gait speed

Objective: To investigate the relations between premorbid and current mental ability, mood, and white matter signal abnormalities detected by T2 weighted brain magnetic resonance imaging (MRI) and impairment of balance and mobility in older adults. Methods: 97 subjects from the Aberdeen 1921 birth cohort underwent brain MRI, evaluation of balance, and measurement of gait speed. White matter hyperintensities detected on T2 weighted MRI scans were rated by three independent raters on three variables: white matter lesions; periventricular lesions; and brain stem lesions. Results: Decreased gait speed was correlated with impaired visual acuity (p = 0.020), shorter stature (p = 0.008), a lower childhood IQ (p = 0.030), a lower current Raven’s progressive matrices score (Raven score) (p < 0.001), a higher hospital anxiety and depression scale (HADS) score (p = 0.004), and an increased grade of brain stem lesions on MRI. Inability to balance was correlated with Raven score (p = 0.042), brain stem lesions (p = 0.003), white matter lesions (p = 0.003), and periventricular lesions (p = 0.038). Binary logistic regression identified brain stem lesions (odds ratio (OR) 0.22; 95% confidence interval 0.09 to 0.54) and HADS depression score (OR 0.75; 0.58 to 0.97) as the only significant associations with balance. Structural equation modelling detected an association between two latent traits representing white matter disease and an integrating function, respectively. Conclusions: In this cohort, white matter lesions, periventricular lesions, and brain stem lesions were associated with impaired balance. Current mental ability was strongly related to gait speed. There appears to be a concordance between motor skills and intellect in old age, which is degraded by white matter disease.
Knee-straining work activities, self-reported knee disorders and radiographically determined knee osteoarthritis.

OBJECTIVES Earlier studies indicate an increased risk of knee disorders in trades with knee-straining work positions, but no dose-response correlation has yet been documented. This study examined whether self-reported knee complaints and radiologically diagnosed knee osteoarthritis are dose-related to kneeling and squatting work positions. METHODS Worktasks for floor layers and carpenters were video-recorded, and the time spent in knee-straining work positions was quantified. A questionnaire study included 133 floor layers, 506 carpenters, and 327 compositors, all without earlier acute knee trauma. Radiological examinations were carried out on a stratified sample (N = 150) from the questionnaire study. The individual exposure was calculated from the amount of knee strain quantified in the video-recorded worktasks, the self-reported time spent in the worktask, and the number of years in the trade. Statistical analyses were carried out with a binary logistic regression model, adjusting for age, body mass index, smoking, and knee-straining sports activities. RESULTS The odds ratios for self-reported knee complaints and radiographically determined knee osteoarthritis were increased in relation to the degree of knee-straining work demands for workers with low-to-moderate, high, and very high exposure to knee-straining work demands in a comparison with the reference group, without knee-stressing work activities. CONCLUSIONS The results indicate that there is a dose-response correlation between knee-straining work activities and the development of self-reported knee complaints and radiologically diagnosed knee osteoarthritis.
An Energy-Efficient Cooperative SFBC-OFDM System Using Subcarrier Permutation

Cooperative orthogonal frequency division multiplexing (OFDM) systems have been shown to be fertile in both spatial and frequency diversities and can provide high transmission throughputs. In this paper, we aim at developing a cooperative space-frequency block coded (SFBC) OFDM system by using Alamouti's coding scheme. With the selective decode-and- forward relaying strategy, we first derive the equivalent channel power gain in a cooperative SFBC-OFDM system based on the channel state information and the predefined transmission rate on each subcarrier. Then, we employ subcarrier permutation to find the optimal pairing mechanism between the broadcasting phase and the forwarding phase such that the total transmission power is minimized. Simulation results show that the proposed cooperative SFBC-OFDM system using subcarrier permutation can provide obvious performance improvement over existing cooperative OFDM systems without SFBC.
Evaluation of automatic video captioning using direct assessment

We present Direct Assessment, a method for manually assessing the quality of automatically-generated captions for video. Evaluating the accuracy of video captions is particularly difficult because for any given video clip there is no definitive ground truth or correct answer against which to measure. Metrics for comparing automatic video captions against a manual caption such as BLEU and METEOR, drawn from techniques used in evaluating machine translation, were used in the TRECVid video captioning task in 2016 but these are shown to have weaknesses. The work presented here brings human assessment into the evaluation by crowd sourcing how well a caption describes a video. We automatically degrade the quality of some sample captions which are assessed manually and from this we are able to rate the quality of the human assessors, a factor we take into account in the evaluation. Using data from the TRECVid video-to-text task in 2016, we show how our direct assessment method is replicable and robust and scales to where there are many caption-generation techniques to be evaluated including the TRECVid video-to-text task in 2017.
Using Bayesian Belief Networks to Predict Change Propagation in Software Systems

During software evolution, developers modify various modules to handle new requirements or to fix existing bugs. Such changes usually propagate to related modules throughout the system. Program comprehension techniques are able to predict this change propagation phenomenon. In this paper, we introduce a novel approach that predicts the possible affected system modules, given a change in the system. We use Bayesian Belief Networks as a probabilistic tool to make such predictions in a systematic way. This novel technique mainly relies on two sources of information: dependency metrics (calculated using static analysis) and change history extracted from a version control repository. We evaluate our approach by examining all significant revisions of Azureusl, an open-source Java system. The results show that the predicted change probabilities reflect actual module changes even in the early stages of the software development.
Historical perspective on the synonymization of the four major pest species belonging to the Bactrocera dorsalis species complex (Diptera, Tephritidae)

Abstract An FAO/IAEA-sponsored coordinated research project on integrative taxonomy, involving close to 50 researchers from at least 20 countries, culminated in a significant breakthrough in the recognition that four major pest species, Bactrocera dorsalis, Bactrocera philippinensis, Bactrocera papayae and Bactrocera invadens, belong to the same biological species, Bactrocera dorsalis. The successful conclusion of this initiative is expected to significantly facilitate global agricultural trade, primarily through the lifting of quarantine restrictions that have long affected many countries, especially those in regions such as Asia and Africa that have large potential for fresh fruit and vegetable commodity exports. This work stems from two taxonomic studies: a revision in 1994 that significantly increased the number of described species in the Bactrocera dorsalis species complex; and the description in 2005 of Bactrocera invadens, then newly incursive in Africa. While taxonomically valid species, many biologists considered that these were different names for one biological species. Many disagreements confounded attempts to develop a solution for resolving this taxonomic issue, before the FAO/IAEA project commenced. Crucial to understanding the success of that initiative is an accounting of the historical events and perspectives leading up to the international, multidisciplinary collaborative efforts that successfully achieved the final synonymization. This review highlights the 21 year journey taken to achieve this outcome.
A Model-based Approach for Merging Prioritized Knowledge Bases in Possibilistic Logic

This paper presents a new approach for merging prioritized knowledge bases in possibilistic logic. Our approach is semantically defined by a model-based merging operator in propositional logic and the merged result of our approach is a normal possibility distribution. We also give an algorithm to obtain the syntactical counterpart of the semantic approach. The logical properties of our approach are considered. Finally, we analyze the computational complexity of our merging approach.
High cholesterol may protect against infections and atherosclerosis.

Many researchers have suggested that the blood lipids play a key role in the immune defence system.1–,21 There is also a growing understanding that an inflammatory response of the arterial intima to injury is a crucial step in the genesis of atherosclerosis. and that infections may be one type of such injury.22 These two concepts are difficult to harmonize with the low-density-lipoprotein (LDL) receptor hypothesis, according to which high LDL cholesterol is the most important cause of atherosclerosis. However, the many observations that conflict with the LDL receptor hypothesis, may be explained by the idea that high serum cholesterol and/or high LDL is protective against infection and atherosclerosis. Lipopolysaccharide, or endotoxin, the main pathogenic factor of Gram-negative bacteria, binds rapidly to lipoproteins,6 mainly LDL,7 and lipoprotein-bound endotoxin is unable to activate the secretion of various cytokines by monocytes in vitro . 6,7,,10 Also, Staphylococcus aureus α-toxin, a toxin produced by most pathogenic Staphylococcus strains and causing damage to a wide variety of cells, is bound and almost totally inactivated by human serum and purified LDL, as estimated by haemolytic titration.3 Mice with hypercholesterolaemia due to LDL-receptor deficiency, challenged with bacterial endotoxin, had an 8-fold increased LD50, and a significantly lower and delayed mortality after injection with Gram-negative bacteria, compared with control mice.15 Also, rats made hypolipidaemic with 4-aminopyrolo-(3,4-D)pyrimide or estradiol had a greater increase in cytokine levels and markedly increased endotoxin-induced mortality compared to normal rats, and administration of exogenous lipoprotein reduced their mortality substantially.12 In apparent contradiction, is a study of mice infected with Trypanosoma cruzi . These mice developed vasculitis and also atherosclerosis, but the latter was seen only if they were fed a Western-type high-fat diet in addition. However, total serum cholesterol (t-C) did not …
Carbonic anhydrase III is insufficient in muscles of myasthenia gravis patients

Myasthenia gravis (MG) is considered as an autoimmune disease mainly mediated by antibodies against acetylcholine receptor. In recent years, other targets related to MG have been the subject of interest. Our previous research found that protein P25 was lower in muscles of MG patients using two-dimensional electrophoresis. In present study, anti-serum to P25 was prepared, immunohistochemistry and ATPase staining revealed that P25 was a muscle specific cytosolic protein and was mainly distributed in type I muscle fibers. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and precise molecular weight derived from mass spectrometer identified P25 as carbonic anhydrase III (CA III). Some members of CA family are related to autoimmune diseases and CA III is recently reported to be involved in rheumatoid arthritis. The results of immunoblot in this report showed that the level of CA III is specifically insufficient in the skeletal muscle of MG patients. The possible roles that CA III play in MG need further elucidation.
Process capability study of ultrasonic machining for titanium alloys

The purpose of the present investigations is to study the process capability of ultrasonic machining (USM) for titanium and its alloys. For the analysis purpose, Taguchi model of material removal rate (MRR), tool wear rate (TWR) and surface roughness (SR) for USM of titanium and its alloys has been used. Relationships between MRR, TWR, SR and other controllable machining parameters (power rating, tool type, slurry concentration, slurry type, slurry temperature and slurry size) have been deduced. The results of study suggest that the USM process lies in ±4.5 sigma (σ) limit as regard to MRR and TWR is concerned. For SR process capability is ±5.1 σ at the best settings of input parameters while machining of titanium alloys.
Medicines used in respiratory diseases only seen in children

Detailed literature searches were carried out in seven respiratory disease areas. Therapeutic evidence for efficacy of medicinal products was assessed using the Grades of Recommendation, Assessment and Evaluation (GRADE) methodology, as well as an assessment of safety and side-effects. Systemic corticosteroids may reduce the development of bronchopulmonary dysplasia but have serious side-effects. Antioxidants need further study to demonstrate whether they have long-term benefits. Treatments for acute bronchiolitis have shown little benefit but new antiviral and monoclonal antibodies need further assessment. Well-constructed studies are needed to confirm the value of inhaled corticosteroids and/or montelukast in the management of viral-induced wheeze. Corticosteroids are the treatment of choice in croup. Minimal or no information is available for the treatment of congenital lung abnormalities, bronchiolitis obliterans and interstitial lung disease.
Midbrain dopamine neurons sustain inhibitory transmission using plasma membrane uptake of GABA, not synthesis

Synaptic transmission between midbrain dopamine neurons and target neurons in the striatum is essential for the selection and reinforcement of movements. Recent evidence indicates that nigrostriatal dopamine neurons inhibit striatal projection neurons by releasing a neurotransmitter that activates GABAA receptors. Here, we demonstrate that this phenomenon extends to mesolimbic afferents, and confirm that the released neurotransmitter is GABA. However, the GABA synthetic enzymes GAD65 and GAD67 are not detected in midbrain dopamine neurons. Instead, these cells express the membrane GABA transporters mGAT1 (Slc6a1) and mGAT4 (Slc6a11) and inhibition of these transporters prevents GABA co-release. These findings therefore indicate that GABA co-release is a general feature of midbrain dopaminergic neurons that relies on GABA uptake from the extracellular milieu as opposed to de novo synthesis. This atypical mechanism may confer dopaminergic neurons the flexibility to differentially control GABAergic transmission in a target-dependent manner across their extensive axonal arbors. DOI: http://dx.doi. org/10.7554/eLife.01936. 001
Crystal structure of the extracellular cholinesterase-like domain from neuroligin-2

Neuroligins (NLs) are catalytically inactive members of a family of cholinesterase-like transmembrane proteins that mediate cell adhesion at neuronal synapses. Postsynaptic neuroligins engage in Ca2+-dependent transsynaptic interactions via their extracellular cholinesterase domain with presynaptic neurexins (NRXs). These interactions may be regulated by two short splice insertions (termed A and B) in the NL cholinesterase domain. Here, we present the 3.3-Å crystal structure of the ectodomain from NL2 containing splice insertion A (NL2A). The overall structure of NL2A resembles that of cholinesterases, but several structural features are unique to the NL proteins. First, structural elements surrounding the esterase active-site region differ significantly between active esterases and NL2A. On the opposite surface of the NL2A molecule, the positions of the A and B splice insertions identify a candidate NRX interaction site of the NL protein. Finally, sequence comparisons of NL isoforms allow for mapping the location of residues of previously identified mutations in NL3 and NL4 found in patients with autism spectrum disorders. Overall, the NL2 structure promises to provide a valuable model for dissecting NL isoform- and synapse-specific functions.
Ataxia-telangiectasia: phenotype/genotype studies of ATM protein expression, mutations, and radiosensitivity.

Previous studies on a limited number of ataxia-telangiectasia (A-T) patients with detectable levels of intracellular ATM protein have suggested a genotype/phenotype correlation. We sought to elucidate this possible correlation by comparing ATM protein levels with mutation types, radiosensitivity, and clinical phenotype. In this study, Western blot analysis was used to measure ATM protein in lysates of lymphoblastoid cell lines (LCLs) from 123 unrelated A-T patients, 10 A-T heterozygotes, and 10 patients with phenotypes similar to A-T. Our Western blot protocol can detect the presence of ATM protein in as little as 1 microg of total protein; at least 25 microg of protein was tested for each individual. ATM protein was absent in 105 of the 123 patients (85%); most of these patients had truncating mutations. The remaining subset of 18 patients (15%) had reduced levels of normal-sized ATM protein; missense mutations were more common in this subset. We used a colony survival assay to characterize the phenotypic response of the LCLs to radiation exposure; patients with or without detectable ATM protein were typically radiosensitive. Nine of 10 A-T heterozygotes also had reduced expression of ATM, indicating that both alleles contribute to ATM protein production. These data suggest that although ATM-specific mRNA is abundant in A-T cells, the abnormal ATM protein is unstable and is quickly targeted for degradation. We found little correlation between level of ATM protein and the type of underlying mutation, the clinical phenotype, or the radiophenotype.
Investigation into UDP-Glucuronosyltransferase (UGT) Enzyme Kinetics of Imidazole- and Triazole-Containing Antifungal Drugs in Human Liver Microsomes and Recombinant UGT Enzymes

Imidazoles and triazoles represent major classes of antifungal azole derivatives. With respect to UDP-glucuronosyltransferase (UGT) enzymes, the drug metabolism focus has mainly concentrated on their inhibitory effects with little known about azoles as substrates for UGTs. N-Glucuronide metabolites of the imidazole antifungals, tioconazole and croconazole, have been reported, but there are currently no reports of N-glucuronidation of triazole antifungal agents. In this study, evidence for glucuronidation of azole-containing compounds was studied in human liver microsomes (HLM). When a glucuronide metabolite was identified, azoles were incubated in 12 recombinant UGT (rUGT) enzymes, and enzyme kinetics were determined for the UGT with the most intense glucuronide peak. Six imidazole antifungals, three triazoles, and the benzodiazepine alprazolam (triazole) were evaluated in this study. All compounds investigated were identified as substrates of UGT. UGT1A4 was the main enzyme involved in the metabolism of all compounds except for fluconazole, which was mainly metabolized by UGT2B7, probably mediating its O-glucuronide metabolism. UGT1A3 was also found to be involved in the metabolism of all imidazoles but not triazoles. In both HLM and rUGT Km values were lower for imidazoles (14.8–144 μM) than for triazoles (158–3037 μM), with the exception of itraconazole (8.4 μM). All of the imidazoles studied inhibited their own metabolism at high substrate concentrations. In terms of UGT1A4 metabolism, itraconazole showed kinetic features characteristic of imidazole rather than triazole antifungals. This behavior is attributed to the physicochemical properties of itraconazole that are similar to those of imidazoles in terms of clogP.