Miracle-dz/UniFAR-FTUs huggingface dataset:
Myrothecium verrucaria bilirubin oxidase and its mutants for potential copper ligands.

Bilirubin oxidase (EC:1.3.3.5) purified from a culture medium of Myrothecium verrucaria MT-1 (authentic enzyme) catalyzes the oxidation of bilirubin to biliverdin in vitro and recombinant enzyme (wild type) was obtained by using an overexpression system of the bilirubin oxidase gene with Aspergillus oryzae harboring an expression vector. The absorption and ESR spectra showed that both bilirubin oxidases are multicopper oxidases containing type 1, type 2, and type 3 coppers similar to laccase, ascorbate oxidase, and ceruloplasmin. Site-directed mutagenesis has been performed for the possible ligands of each type of copper. In some mutants, Cys457 --> Val, Ala, His94 --> Val, and His134.136 --> Val, type 1 and type 2 copper centers were perturbed completely and the enzyme activity was completely lost. Differing from the holoenzyme, these mutants showed type 3 copper signals. However, the optical and magnetic properties characteristic of type 1 copper were retained even by mutating one of the type 1 copper ligands, i.e., a mutant, Met467 --> Gly, showed a weak but apparent enzyme activity. A double mutant His456.458 --> Val had only type 1 Cu, showing a blue band at 600 nm (epsilon = 1.6 x 10(3)) and an ESR signal with very narrow hyperfine splitting (A parallel = 7.2 x 10(-)3 cm-1). Since the type 2 and type 3 coppers are not present, the mutant did not show enzyme activity. These results strongly imply that the peculiar sequence in bilirubin oxidase, His456-Cys457-His458, forms an intramolecular electron-transfer pathway between the type 1 copper site and the trinuclear center composed of the type 2 and type 3 copper sites.
Characteristics of effective clinical teachers.

OBJECTIVES Defining what makes an exceptional teacher is challenging. This study's objectives were to identify teaching attributes that residents and faculty value most and to determine whether the opinions of residents and faculty differed. METHODS A list of 15 teaching attributes was distributed to residents and faculty at eight family medicine residency programs. Respondents were asked to indicate the three most important and the three least important attributes of effective clinical educators. RESULTS Overall response rates were 58% for residents and 65% for faculty. Residents and faculty agreed that being enthusiastic and having clinical competence are important attributes and that scholarly activity is not as important. Residents felt it is important for an educator to respect their autonomy and independence as clinicians, whereas faculty members felt that this was among the least important traits. Faculty felt that serving as a role model worth emulating was important, but residents ranked this at the bottom of their list. Residents placed a higher premium on a faculty member's ability to answer questions clearly and explain difficult topics (labeled "clarity" in our study) and felt more strongly that it was important for quality educators to be readily available and able to provide a safe, nonjudgmental, nonthreatening learning environment. CONCLUSIONS There are areas of agreement and disagreement between faculty and residents about attributes of effective clinical teachers. With the implementation of competency-based assessment systems, it will become important to determine which attributes actually promote the development of competence among learners, thereby allowing the encouragement of those attributes.
Salivary Histatin 5 Induces Non-lytic Release of ATP fromCandida albicans Leading to Cell Death*

Salivary histatins are potent in vitro antifungal proteins and have promise as therapeutic agents against oral candidiasis. We performed pharmacological studies directed at understanding the biochemical basis of Hst 5 candidacidal activity. Three inhibitors of mitochondrial metabolism: carbonyl cyanidep-chlorophenylhydrazone, dinitrophenol, and azide inhibited Hst 5 killing of Candida albicans, while not inhibiting cellular ATP production. In contrast, Hst 5 caused a drastic reduction of C. albicans intracellular ATP content, which was a result of an efflux of ATP. Carbonyl cyanidep-chlorophenylhydrazone, dinitrophenol, and azide inhibited Hst 5-induced ATP efflux, thus establishing a correlation between ATP release and cell killing. Furthermore, C. albicans cells were respiring and had polarized membranes at least 80 min after ATP release, thus implying a non-lytic exit of cellular ATP in response to Hst 5. Based on evidence that transmembrane ATP efflux can occur in the absence of cytolysis through a channel-like pathway and that released ATP can act as a cytotoxic mediator by binding to membrane purinergic receptors, we evaluated whether extracellular ATP released by Hst 5 may have further functional role in cell killing. Consistent with this hypothesis, purinergic agonists BzATP and adenosine 5′O-(thiotriphosphate) induced loss of C. albicans cell viability and purinergic antagonists prevented Hst 5 killing.
Ultrastructure of substance P‐immunoreactive terminals and their relation to vascular smooth muscle cells of rat small mesenteric arteries

Mesenteric arteries of the rat are surrounded by a plexus of primary afferent nerve terminals which contain both substance P (SP) and calcitonin gene‐related peptide (CGRP). The ultrastructural arrangement of the innervation was studied in second‐order branches of the rat mesenteric artery using immunohistochemical labelling with antibodies against SP. The structure and distribution of SP‐immunoreactive (SP+) and SP‐negative (SP−, i.e., virtually all noradrenergic) axons and their terminals within the adventitia of the artery have been determined. Sixteen percent of axons and 22% of varicosities in the perivascular plexus were SP+. Most of the SP+ varicosities lay between 0.4 and 2 μm from the smooth muscle cells, whereas most SP− varicosities lay much closer to the vessel (i.e., <1 μm). SP+ varicosities typically contained the same number and size of small synaptic vesicles and mitochondria as SP− varicosities, but there were more large dense‐cored vesicles in the SP+ varicosities. Unlike SP− varicosities, the peptidergic varicosities did not show clustering of synaptic vesicles toward one part of the axon membrane, and none of them formed junctions with the smooth muscle cells. Close relationships between SP+ and SP− varicosities lacked any detectable structural specialization. The arrangement of SP+ (primary afferent) terminals and their association with vascular smooth muscle cells indicates that peptide released from afferent terminals must diffuse further than noradrenaline from sympathetic terminals to reach the vascular smooth muscle. J. Comp. Neurol. 416:277–290, 2000. © 2000 Wiley‐Liss, Inc.
When Work Calls—Associations Between Being Contacted Outside of Regular Working Hours for Work-Related Matters and Health

Boundaries between work and private life are diminishing, but little is known on how this influences worker health. Therefore, we examined the association between work-related contacts outside of regular working hours by e-mail or phone and self-reported health in a representative sample of European employees (n = 23 760). The risk of reporting ≥1 health problem(s) was increased in workers contacted sometimes (odds ratio [OR]: 1.16, 95% confidence interval [CI]: 1.06–1.27) or often (OR: 1.23, 95% CI: 1.12–1.34) as compared with never, controlling for several demographic and workplace characteristics. Further research is needed to quantify work and nonwork patterns and their health effects.
Dairy consumption and 10-y total and cardiovascular mortality: a prospective cohort study in the Netherlands.

BACKGROUND The consumption of dairy products (milk, cheese, and butter) has been positively associated with the risk of ischemic heart disease (IHD), stroke, and total mortality because of the saturated fat content of these products; and protective effects against these outcomes have been attributed to the calcium content and low-fat choices of dairy products. However, robust evidence on the net effect of dairy product consumption on mortality is limited. OBJECTIVE The objective was to investigate the association between dairy product consumption and the risk of death (from all causes, IHD, and stroke) in the Netherlands Cohort Study (NLCS). DESIGN The NLCS was initiated in 120,852 men and women aged 55-69 y at baseline in 1986. After 10 y of follow-up, 16,136 subjects with complete dietary information had died. Twenty-nine percent (men) and 22% (women) of these deaths were due to IHD or stroke. The validated 150-item food-frequency questionnaire provided detailed information on dairy products. RESULTS Multivariate survival analyses following a case-cohort approach showed only a few statistically significant, but mostly weak, associations. A slightly increased risk of all-cause and IHD mortality was found for both butter and dairy fat intake (per 10 g/d; rate ratio(mortality): 1.04; 95% CI: 1.01, 1.06) only in women. Fermented full-fat milk was inversely associated with all-cause and nonsignificantly with stroke mortality in both sexes. CONCLUSIONS The role of dairy product consumption in mortality generally appeared to be neutral in men. In women, dairy fat intake was associated with slightly increased all-cause and IHD mortality. More research is warranted on a possible protective effect of fermented milk on stroke mortality.
Influence of nano-AlN particles on thermal conductivity, thermal stability and cure behavior of cycloaliphatic epoxy/trimethacrylate system

We have prepared a series of nano-sized aluminium nitride (nano-AlN)/cycloaliphatic epoxy/trimethacrylate (TMPTMA) systems and investigated their morphology, thermal conductivity, thermal stability and curing behavior. Exper- imental results show that the thermal conductivity of composites increases with the nano-AlN filler content, the maximum value is up to 0.47 W/(m! K). Incorporation of a small amount of the nano-AlN filler into the epoxy/TMPTMA system improves the thermal stability. For instance, the thermal degradation temperature at 5% weight loss of nano-AlN/ epoxy/TMPTMA system with only 1 wt% nano-AlN was improved by �8oC over the neat epoxy/TMPTMA system. The effect of nano-AlN particles on the cure behavior of epoxy/TMPTMA systems was studied by dynamic differential scan- ning calorimetry. The results showed that the addition of silane treated nano-AlN particles does not change the curing reac- tion mechanism and silane treated nano-AlN particles could bring positive effect on the processing of composite since it needs shorter pre-cure time and lower pre-temperature, meanwhile the increase of glass transition temperature of the nanocomposite improves the heat resistance.
Assessing extent of single stranded DNA damage in oral mucosal cells of patients with oral squamous cell carcinoma and its correlation with TNM staging.

CONTEXT This study was carried out on the assumption that oral mucosal cells might show DNA damage in oral squamous cell carcinoma (OSCC). AIMS To evaluate the extent of DNA damage in oral smears of patients with OSCC and determine correlation if any of the extent of DNA damage to TNM staging of oral cancer. SETTINGS AND DESIGN A randomized controlled study at a regional cancer centre was designed for this project. Smears were taken from lesion proper of 30 patients with OSCC and from the buccal mucosa of 30 normal healthy volunteers. MATERIALS AND METHODS Collected cells were centrifuged and single-cell gel electrophoresis (SCGE) assay was performed. DNA damage was visualized under a fluorescent microscope. Statistical analysis used : Mean DNA damage levels of both the groups were measured and statistically analyzed with students' test. The extent of DNA damage was correlated with the TNM stages by employing the one way ANOVA 'F' technique. RESULTS High statistical significance (P < 0.0001) was found in DNA damage levels between control and study groups. A stepwise increase in DNA damage levels with high statistical significance (P < 0.005) was also found between all the TNM stages. CONCLUSIONS Statistically significant increased DNA damage levels in OSCC patients and their correlation to clinical staging suggest that comet assay may be used effectively to assess the prognosis of OSCC.
Leads for cardiac resynchronization therapy: where and how many?

This editorial refers to ‘A randomized study of haemodynamic effects and left ventricular dyssynchrony in right ventricular apical vs. high posterior septal pacing in cardiac resynchronization therapy’, by H.M. Kristiansen et al., published in this issue on pages 506–516 and ‘A randomized double-blind crossover trial of triventricular versus biventricular pacing in heart failure’, by D.P.S. Rogers et al., published in this issue on pages 495–505.
Cell response of nanographene platelets to human osteoblast-like MG63 cells.

The biologic/cytotoxic effects of dispersed nanographene platelets (NGPs) on human osteosarcoma cells (MG63 cell line) were first studied by examining cell viability, cycle, apoptosis, change in morphology, lactate dehydrogenase (LDH) release, alkaline phosphatase (ALP) activity, and inflammation. The results shown that the cell cytotoxicity of the dispersed NGPs exhibited dose-dependent characters, which had no obvious cytotoxic effects to MG63 cells at the concentration less than 10 μg mL(-1), whereas could postpone cell cycle, promote cell apoptosis, damage cell microstructure, induce serious tumor necrosis factor-α expression and greatly reduce ALP activity of MG63 cells at higher concentration of NGPs (>10 µg mL(-1)). Besides, NGPs had little influence on the LDH leakage. The cytotoxic mechanism of NGPs to MG63 cells was speculated to be intracellular activity with no physical damage of plasma membrane.
Truthmakers, entailment and necessity

Australian Realist analytic philosophy is full of claims about truthmakers and truthmaking. In this paper, I seek to show that a number of intuitions about truthmaking are jointly inconsistent, and that some common attempts at resolving the inconsistency are unsatisfying. Finally, I propose an account of truthmaking which resolves the tensions as best as possible. This account has great aanities with both relevant entailment and situation semantics. This note can be seen as an apologetic for relevant entailment for those who are familiar with truthmaking, or as an introduction to truthmaking for those familiar with logic. Either way, it is an attempt to apply modern logical methods and insights to a philosophical problem.
Befriending as an intervention for chronic depression among women in an inner city

Background Earlier work on the protective role of social support in onset and course of depressive disorder suggested that its provision might be relevant for outcome. Aims To evaluate volunteer befriending as an intervention among women with chronic depression in inner London. Method A randomised controlled trial, with awaiting list control design, with outcome measured as Present State Examination (PSE)-based full or partial remission after one year. Results A statistically significant effect upon remission was found for befriending. Other treatments monitored naturalistically did not relate to remission, nor did initial duration of chronic episode or comorbidity, but there was an association with initial PSE score. The findings are discussed in relation to standard drug-trial results and to another befriending intervention with the elderly. Conclusions The results are not unpromising. Additional trials with less restricted intake conditions, and in more naturalistic general practice settings, might confirm volunteer befriending as a useful adjunct to current treatments.
Characterization of Zebrafish Cx43.4 Connexin and its Channels

Connexins (Cx) form intercellular junctional channels which are responsible for metabolic and electrical coupling. We report here on the biochemical and immunohistochemical characterization of zebrafish connexin zfCx43.4, an orthologue of mammalian and avian Cx45, and the electrophysiological properties of junctional channels formed by this protein. The investigations were performed on transfected COS‐7 cells or HeLa cells. Using site‐directed antibodies, zfCx43.4 cDNA (GenBank accession no. X96712) was demonstrated to code for a protein with a Mr of 45 000. In transfected cells, zfCx43.4 was localized in cell‐cell contact areas as expected for a gap junction protein. zfCx43.4 channels were shown to transfer Lucifer Yellow. The multichannel currents were sensitive to the transjunctional voltage (Vj). Their properties were consistent with a two‐state model and yielded the following Boltzmann parameters for negative/positive Vj: Vj,0= ‐38.4/41.9 mV; gj,min= 0.19/0.18; z = 2.6/2.3. These parameters deviate somewhat from those of zfCx43.4 channels expressed in Xenopus oocytes and from those of Cx45, an orthologue of zfCx43.4, expressed in mammalian cells or Xenopus oocytes. Conceivably, the subtle differences may reflect differences in experimental methods and/or in the expression system. The single channel currents yielded two prominent levels attributable to a main conductance state (γj,main= 33.2 ± 1.5 pS) and a residual conductance state (γj,residual= 11.9 ± 0.6 pS).
Cardiac manifestations of rheumatoid arthritis: a case-control transesophageal echocardiography study in 30 patients.

OBJECTIVES Current knowledge of the cardiac manifestations of rheumatoid arthritis (RA) stems only from clinical and transthoracic echocardiography (TTE) studies. To determine the incidence and type of heart lesions in RA, we coupled TTE with transesophageal echocardiography (TEE), which is more sensitive and more accurate. METHODS Thirty unselected RA patients (26 women and 4 men aged 27 to 84 years, with a mean age of 57.8+/-15.1 years) free of known progressive heart disease underwent a chest radiograph, an electrocardiogram, laboratory tests, and TTE coupled with TEE. Results were compared with those in age- and sex-matched patients who were free of rheumatic disease and who underwent TEE to investigate a neurologic or cardiologic disorder. RESULTS Mitral regurgitation (MR) was evidenced in 24 cases (80%). Among the controls, only 11 (37%) had MR (P < 0.001). Aortic regurgitation was found in 10 cases (33%), versus 7 controls (not significant-NS). Seven cases (23%) versus only 2 controls (7%) had tricuspid valve abnormalities (NS). Pericarditis was found in 4 cases (13%) and in none of the controls. Eleven cases had evidence of cardiomyopathy (37%) and 12 (40%) had atheroma of the aorta, this last being missed by TTE in 10 patients. Echo-generating nodules were seen on a mitral valve in 2 cases and on an aortic valve in 1. We found no correlations linking cardiac lesions to clinical or laboratory features of RA. CONCLUSION Our study demonstrated that cardiac involvement, particularly of the mitral valve, is extremely common in RA patients.
Two Experiences of Blended Learning Process on Engineering Education

The paper presents the experience developed by the authors in two virtual learning platforms oriented to learning about helicopters in aerospace engineering. The first course on OCW-UPM project will be explained, and as well as the evolution towards a step further in open education resources with the course "Introduction to Engineering Helicopter" in edX. The results obtained in each course will be analyzed, and the conclusions taken into account.
Complement plays an essential role in shock following intestinal ischaemia in rats

Intestinal ischaemia lasting more than 30 min in rats causes fatal systemic shock. Systemic shock was suppressed by preadministration of cobra venom factor (CVF), which reduced the serum complement to less than 5% of the normal level, indicating that complement is involved in the syndrome. After complement activation, anaphylatoxins such as C3a and C5a are generated, and their activity is restricted by carboxypeptidases which remove C‐terminal arginine from such bioactive peptides. As expected, preadministration of a carboxypeptidase inhibitor enhanced the systemic shock induced by the intestinal ischaemia. However, when the complement level was suppressed by CVF treatment, no fatal systemic shock was induced by the intestinal ischaemia even with preadministration of the carboxypeptidase inhibitor. These results indicate that complement plays a crucial role in systemic shock induced by intestinal ischaemia, and that anaphylatoxins generated by the complement activation should be involved in induction of the shock syndrome.
Performance evaluation of LoRa networks in a smart city scenario

Low-Power Wide Area Networks (LPWANs) are continuously gaining momentum as fundamental enablers of the Internet of Things (IoT) paradigm. These networks provide longrange coverage to end nodes, exploiting license-free frequency bands. The focus of this work is on one of the most prominent LPWAN technologies: LoRa™. We implemented a new ns-3 module to study the performance of a LoRa-based IoT network in a typical urban scenario. Simulation results show that a LoRa network can scale well, achieving packet success rates above 95% in presence of a number of end devices in the order of 104.
Zevalin and BEAM (Z‐BEAM) versus rituximab and BEAM (R‐BEAM) conditioning chemotherapy prior to autologous stem cell transplantation in patients with mantle cell lymphoma

Early relapse is common in patients with mantle cell lymphoma (MCL) highlighting the unmet need for further improvement of therapeutic options for these patients. CD20 inhibition combined with induction chemotherapy as well as consolidation with high‐dose chemotherapy (HDCT) is increasingly considered cornerstones within current therapy algorithms of MCL whereas the role of radioimmunotherapy is unclear. This retrospective single center study compared 46 consecutive MCL patients receiving HDCT in first or second remission. Thirty‐five patients had rituximab and BEAM (R‐BEAM), and 11 patients received ibritumomab tiuxetan (Zevalin®), an Yttrium‐90 labeled CD20 targeting antibody, prior to BEAM (Z‐BEAM) followed by autologous stem cell transplantation (ASCT). We observed that the 5‐year overall survival (OS) in the R‐BEAM and Z‐BEAM groups was 55% and 71% (p = 0.288), and the 4‐year progression free survival (PFS) was 32% and 41%, respectively (p = 0.300). There were no treatment related deaths in both groups, and we observed no differences in toxicities, infection rates or engraftment. Our data suggest that the Z‐BEAM conditioning regimen followed by ASCT is well tolerated, but was not associated with significantly improved survival compared to R‐BEAM. Copyright © 2015 John Wiley & Sons, Ltd.
The Renin-Angiotensin-Aldosterone System: Approaches to Guide Angiotensin-Converting Enzyme Inhibition in Patients with Coronary Artery Disease

Drugs that modulate the renin-angiotensin-aldosterone system (RAAS) play an important role in modern cardiovascular prevention strategies. Inhibitors of the RAAS, in particular angiotensin-converting enzyme (ACE) inhibitors, have been proven to be beneficial in specific patient groups, including patients with hypertension, heart failure, diabetes mellitus and stable coronary artery disease. Although clinical trials demonstrated a rather consistent beneficial effect of ACE inhibitors across groups of patients based on clinical characteristics, the variability in treatment response on the individual patient level is extensive. Recent publications suggest that genetic polymorphisms in the RAAS are related to cardiovascular risk. Genetic variability also seems associated with the response to ACE inhibitor therapy, and can probably be used to tailor treatment. This review discusses several approaches to guide ACE inhibitor therapy in patients with coronary artery disease. In addition, the potential impact of pharmacogenetics regarding this particular topic is highlighted.