Miracle-dz/UniFAR-FTUs huggingface dataset:
Vif Counteracts a Cyclophilin A-Imposed Inhibition of Simian Immunodeficiency Viruses in Human Cells

ABSTRACT Vif is a primate lentiviral accessory protein that is crucial for viral infectivity. Vif counteracts the antiviral activity of host deaminases such as APOBEC3G and APOBEC3F. We now report a novel function of African green monkey simian immunodeficiency virus (SIVagm) Vif that promotes replication of SIVagm in human cells lacking detectable deaminase activity. We found that cyclophilin A (CypA) was excluded from wild-type SIV particles but was efficiently packaged into vif-deficient SIVagm virions. The presence of CypA in vif-defective SIVagm was correlated with reduced viral replication. Infection of CypA knockout Jurkat cells or treatment of Jurkat cells with cyclosporine A eliminated the Vif-sensitive inhibition and resulted in replication profiles that were similar for wild-type and vif-deficient SIVagm. Importantly, the inhibitory effect of CypA was restricted to virus-producing cells and was TRIM5α independent. The abilities of SIVagm Vif to inhibit encapsidation of CypA and to increase viral infectivity were shared by rhesus macaque SIV Vif and thus seem to be general properties of SIV Vif proteins. Exclusion of CypA from SIVagm particles was not associated with intracellular degradation, suggesting a mode of Vif action distinct from that proposed for APOBEC3G. This is the first report of a novel vif-sensitive antiviral activity of human CypA that may limit zoonotic transmission of SIV and the first demonstration of CypA encapsidation into a virus other than human immunodeficiency virus type 1.
Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease.

BACKGROUND Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7. METHODS In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activity Index (CDAI) score of less than 150, with maintenance of remission for at least 2 weeks, and the safety of mongersen treatment. A secondary outcome was clinical response (defined as a reduction of 100 points or more in the CDAI score) at day 28. RESULTS The proportions of patients who reached the primary end point were 55% and 65% for the 40-mg and 160-mg mongersen groups, respectively, as compared with 10% for the placebo group (P<0.001). There was no significant difference in the percentage of participants reaching clinical remission between the 10-mg group (12%) and the placebo group. The rate of clinical response was significantly greater among patients receiving 10 mg (37%), 40 mg (58%), or 160 mg (72%) of mongersen than among those receiving placebo (17%) (P=0.04, P<0.001, and P<0.001, respectively). Most adverse events were related to complications and symptoms of Crohn's disease. CONCLUSIONS We found that study participants with Crohn's disease who received mongersen had significantly higher rates of remission and clinical response than those who received placebo. (Funded by Giuliani; EudraCT number, 2011-002640-27.).
Modeling and simulation of electric car penetration in the distribution power system — Case study

In the coming years electric vehicles will become a part of the transportation system in Europe. This contribution considers the impact of a penetration of electric cars on a distribution grid. For computations load profiles of electric cars (EC) are used by means of real battery measurements. A real low voltage grid data is used to show that security of supply could be ensured when there is a high penetration of electric cars. To forecast a certain charging demand reasonable scenarios are defined. Some conclusions and final remarks summarize the investigation presented in this paper.
Effects of Alternative Coding Strategies on Computer Software Training : Imagery Coding and Procedural Coding

Computer training is vital for improving user interaction with a system. Prior research on computer training indicates that behavior modeling is highly effective for computer skill acquisition and can be further improved by incorporating symbolic coding processes. Building upon dual coding theory, our study proposes two new coding strategies, imagery coding and procedural coding, and examines the effects of those alternative coding strategies on computer learning outcomes relative to textual coding in a modeling-based training context. A training program on a popular computer graphic application was offered in a university setting and attended by 190 trainees. The study results show that modeling-based training can be significantly improved by incorporating the proposed new coding approaches but the specific coding strategy should be carefully chosen depending on the target learning outcome.
Defining “Fake News”

This paper is based on a review of how previous studies have defined and operationalized the term “fake news. ” An examination of 34 academic articles that used the term “fake news” between 2003 and 2017 resulted in a typology of types of fake news: news satire, news parody, fabrication, manipulation, advertising, and propaganda. These definitions are based on two dimensions: levels of facticity and deception. Such a typology is offered to clarify what we mean by fake news and to guide future studies.
The recycling of incinerated sewage sludge ash as a raw material for CaO–Al2O3–SiO2–P2O5 glass-ceramic production

In this paper, the recycling of incinerated sewage sludge ash (ISSA) into glass-ceramic materials by a two-stage sintering cycle of nucleation stage and crystallization stage without any pressure and binder is presented. The parent glasses were subjected to the following nucleation/crystallization temperature and time level: (A) 790°C, 1.0 h/870°C, 1.0–3.0 h; (B) 790°C, 1.0 h/945°C, 1.0–3.0 h and (C) 790°C, 1.0 h/1065°C, 1.0–3.0 h. X-ray power diffraction analysis results revealed that multiple crystalline phases coexisted in the glass-ceramic materials and the crystalline phase compositions were more affected by crystallization temperature than crystallization time. Scanning electron microscopy analysis showed an interlocking microstructure of glass phases and crystals with different sizes and spatial distribution. The glass-ceramics crystallized at 945°C for 2.0 h exhibited optimal properties of density of 2.88 ± 0.08 g/cm3, compression strength of 247 ± 12 MPa, bending strength of 118 ± 14 MPa and water absorption of 0.42 ± 0.04. The leaching concentrations of heavy metals were far lower than the limits required by the regulatory standard of EPA. This paper provides a feasible, low-cost and promising method to produce ISSA-based glass-ceramics and highlights the principal characteristics that must be taken into account to use ISSA correctly in glass-ceramics.
Transnational Knowledge: Its Creation and Distribution Exploiting Entrepreneurship and Organisational Behaviour

96 800x600 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:. 0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:Calibri;} How can knowledge be created (incentivised) and distributed (shared socially) when it is what economists define as a public good - it is very expensive to produce, its use by any one person leaves no less for anyone else and it is generally difficult to sustain property rights over? In economic terms the marginal cost of distributing knowledge is zero and as marginal cost should equal price for optimality, price should be zero. Clearly if the price were zero there will be no incentive for anyone to produce it . So what is to be done?
The isolation and further characterization of the bilirubin tetrapyrroles in bile-containing human duodenal juice and dog gall-bladder bile.

Bilirubin and its conjugates were extracted from either dog gall-bladder bile or bile-containing human duodenal juice into chloroform containing 10mm-tetraheptylammonium chloride. The intact bilirubin tetrapyrroles were then separated by t.l. c. Structural elucidation was made after coupling of the individual pigments with diazonium salts. Four azopigments were detected: azopigment alpha(o) or dipyrrolic azobilirubin; azopigment delta or dipyrrolic azobilirubin monoglucuronide; azopigment alpha(3) or dipyrrolic azobilirubin monoglucoside; and, from dog gall-bladder bile, azopigment alpha(2). The last conjugate required further verification of its structure. After methanolysis, it was shown by combined g.l. c. -mass spectrometry to contain xylose in a 1:1 molar ratio with the azopigments of bilirubin. Human bile contained 86% bilirubin diglucuronide, 7% bilirubin monoglucuronide monoglucoside diester, 4% bilirubin monoglucuronide and 3% bilirubin. Dog gall-bladder bile had a considerably different composition; it contained 47% bilirubin diglucuronide, 40% bilirubin monoglucuronide monoglucoside diester, 8% bilirubin monoglucuronide, 4% bilirubin diglucoside, 1-2% bilirubin and traces of conjugates containing xylose. The total bilirubin content and proportions of the conjugates did not change in bile that was frozen and stored at -20 degrees C under N(2), whereas in the chloroform/tetraheptylammonium chloride extract, similarly stored, total pigment was slowly lost and the diglucuronide conjugate converted into the monoglucuronide.
Evaluation of the Effects of a Machine Failure on the Robustness of a Job Shop System—Proactive Approaches

Researchers are searching for opportunities to organize production systems that save energy and natural resources. Preventive maintenance (PM) is essential for the efficient use of machines and energy saving. Any rework due to a machine failure consumes additional energy, human resources, equipment, spare parts and raw materials. Two criteria—quality robustness (QR) and solution robustness (SR)—are used in order to compute the operational efficiency of the production system in the event of disruption. Any cost criterion can be added to the QR in order to measure losses due to a machine failure. The SR criterion measures a number of changes necessary to adopt the production schedule after the machine failure. Two proactive approaches are compared to compute the operational efficiency. In the predictive-reactive approach, the PM time is predicted and a stable schedule is built. In the proactive-reactive approach, a schedule is achieved for the best sequence of idle times between jobs. The influence of disturbance on both schedules using robustness measures is examined. This paper presents the results of computer simulations for the above approaches. The approaches are compared in order to select a better method of production organization that reduces costs and waste due to machine failure.
CSF3R and CALR mutations in paediatric myeloid disorders and the association of CSF3R mutations with translocations, including t(8; 21)

Mutations in the colony‐stimulating factor 3 receptor (CSF3R) and calreticulin (CALR) genes have been reported in a proportion of adults with myeloproliferative disease. However, little is known about CSF3R or CALR mutations in paediatric myeloid disorders. We analysed CSF3R exons 14 and 17, and CALR exon 9, using direct sequencing in samples of paediatric acute myeloid leukaemia (AML; n = 521), juvenile myelomonocytic leukaemia (JMML; n = 40), myelodysplastic syndrome (MDS; n = 20) and essential thrombocythaemia (ET; n = 21). CSF3R mutations were found in 10 (1·92%) of 521 patients with AML; two in exon 14 (both missense mutations resulting in p.T618I) and eight in exon 17 (three frameshift mutations: p.S715X, p.Q774R, and p.S783Q; and five novel missense mutations: p.Q754K, p.R769H, p.L777F, p.T781I, and S795R). All of the patients with mutations in CSF3R exon 17 had chromosomal translocations, including four with t(8;21). At the time of reporting, seven of these ten patients are alive; three have died, due to side effects of chemotherapy. No CSF3R mutations were found in cases of MDS, JMML or ET. The only mutation found in the CALR gene was a frameshift (p.L367 fs) in one ET patient. We discuss the potential impact of these findings for the leukaemogenesis and clinical features of paediatric myeloid disorders.
B vitamin deficiency promotes tau phosphorylation through regulation of GSK3beta and PP2A.

Neurofibrillary tangles (NFTs), composed of intracellular filamentous aggregates of hyperphosphorylated protein tau, are one of the pathological hallmarks of Alzheimer's disease (AD). Tau phosphorylation is regulated by the equilibrium between activities of its protein kinases and phosphatases; unbalance of these activities is proposed to be a reasonable causative factor to the disease process. Glycogen synthase kinase 3beta (GSK3beta) is one of the most important protein kinase in regulating tau phosphorylation; overexpression of active GSK3beta causes ADlike hyperphosphorylation of tau. Protein phosphatase 2A (PP2A) is the major phosphatase that dephosphorylates tau; it was demonstrated that highly conserved carboxyl-terminal sequence of PP2A C-subunit is a focal point for phosphatase regulation. This is the site of a reversible methyl esterification reaction that controls AB_{alpha}C heterotrimers formation. Here we demonstrate that GSK3beta and PP2A genes were upregulated by inhibiting methylation reactions through B vitamin deficiency. In this condition, methylated catalytic subunit PP2Ac was decreased, leading to reduced PP2A activity. By contrast, we observed GSK3beta protein increase and a modulation in phosphorylation sites that regulate GSK3beta activity. Therefore, one-carbon metabolism alteration seems to be a cause of deregulation of the equilibrium between GSK3beta and PP2A, leading to abnormal hyperphosphorylated tau.
Trichromatic colour opponency in ganglion cells of the rhesus monkey retina.

Two hundred and eleven colour‐opponent ganglion cells were studied in the central 10 degrees of the retina of the rhesus monkey, to determine the inputs which they were receiving from different cone mechanisms. Spectral‐sensitivity measurements in the presence of neutral and coloured back‐grounds showed that 24% of these cells appeared to receive input from all three cone mechanisms. 2. In 3% of the cells, the red‐sensitive cone mechanism opposed the blue‐ and green‐sensitive ones. In 18% of the cells, the blue‐sensitive cone mechanism opposed the green‐ and red‐sensitive ones. In 3% of the cells, the green‐sensitive cone mechanism opposed the blue‐ and red‐sensitive ones. 3. In 12% of the cells receiving opponent green‐ and red‐sensitive cone inputs, responses from the beta‐band of the red‐sensitive cone mechanism could be detected and distinguished from blue‐sensitive cone input. 4. All cells receiving blue‐sensitive cone input appeared to be trichromatic. The retinal distribution of cells with trichromatic input and that of cells with beta‐band responses seemed to parallel the availability of blue‐sensitive cones in the retinal area being considered. 5. The results indicate that trichromatic interactions in the macaque visual system begin in the retina.
Stakeholder Role for Developing a Conceptual Framework of Sustainability in Organization

The purpose of this research is to frame the hierarchical pathway treading the sustainability factors from driving to dependent elements. Hence, this study starts with a brief literature review of the sustainable organization which enables the expansion of sustainability into essential factors. Experts further verified these identified factors and used for framing the hierarchical framework of sustainability in organizations. Total Interpretive Structural Modeling (TISM) has been applied for identifying the driving factor of sustainability and delivering the crucial links among the sustainability factors in organizations. While most of the organizations focus on sustainability by considering the Triple Bottom Line (TBL) framework, this paper has presented the fourth dimension of sustainability which drives sustainability in organizations. The hierarchical relationship is vital to identify the vitality and significance of factors. This in turn provides an efficient approach to achieve sustainability in organizations. The expert’s review has been calculated statistically to validate the factors and conceptual hierarchical framework. Hence, the policymakers make use of sustainability hierarchy to frame a correct and efficient policy for maintaining sustainable practices that help managers to shift their priorities of an organization at the managerial level from economic growth to sustainable development. Finally, the future research direction and the limitation of the study are discussed.
Patrones de consumo alimentario y pobreza monetaria en Colombia

We estimated the inequalities in three patterns of food consumption in Colombian adults (18 and 64 years) related to monetary poverty. An ecological study was conducted, which linked the monetary poverty of 33 geo-demographic units with three consumption patterns obtained through factor analysis using the National Nutrition Situation Survey in Colombia-2010. Using Epidat v. 4.2®, inequality indexes based on ranges, disparity or dispersion were calculated, in disproportionality, based on regression models and those based on the concept of entropy. The determination coefficient (r2) for the fruit-vegetable/dairy pattern was 0.30, 0.08 for the traditional pattern/starch, 0.00 and for the snack pattern. The highest rate ratio was for the fruit-vegetable/dairy pattern (2.61), followed by the ratio for the traditional pattern/starch (0.93), and the lowest for the snack pattern (0.85). Inequality reached the highest Gini coefficient in the pattern of snack consumption (0.26), followed by that reached in the traditional pattern/starch (0.17) and the fruit-vegetable/dairy pattern (0.12). We showed that the greatest inequality occurred in the fruit-vegetable / dairy consumption pattern, it is desirable to increase the adherence to the traditional pattern and decrease the protein intake in the richest population.
Human Interleukin‐3 inhibits the binding of granulocyte‐macrophage colony‐stimulating factor and interleukin‐5 to basophils and strongly enhances their functional activity

The human T cell‐derived cytokines interleukin (IL)‐3, granulocyte‐macrophage colony‐stimulating factor (CM‐CSF), and IL‐5 were examined for their ability to bind specifically to human basophils and to regulate their function. Scatchard analysis of equilibrium binding studies showed that IL‐3 and GM‐CSF, bound to basophils with apparent dissociation constants (KD) = 8 × 10−11M and 3.9 × 10−11M, respectively. Specificity studies under conditions that prevent receptor internalization showed that the binding of IL‐3, GM‐CSF, and IL‐5 was not inhibited by tumor necrosis factor (TNF)‐α, IL‐1β, interferon (IFN)‐γ, or G‐CSF. However, receptors for IL‐3, GM‐CSF, and IL‐5 interacted with each other on the basophil membrane, showing a unique spectrum of cross‐reactivity, with IL‐3 competing for GM‐CSF and IL‐5 binding, whereas GM‐CSF and IL‐5 showed little or no competition for IL‐3 binding. In order to relate the binding properties of these cytokines to function, they were tested for their ability to influence basophil histamine release in an IgE/anti‐IgE‐dependent system. We found a hierarchy in the stimulation of basophil with the order of potency being IL‐3 >GM‐CSF >IL‐5. In addition, IL‐3 stimulated larger amounts of histamine release than GM‐CSF or IL‐5. The observation that IL‐3 interacts with receptors for GM‐CSF and IL‐5 may have a bearing on its stronger functional effects and suggests a major role for IL‐3 in the pathogenesis of hypersensitivity syndromes.
Fos is a preferential target of glucocorticoid receptor inhibition of AP-1 activity in vitro

Several regulatory interactions between the AP-1 and the nuclear hormone receptor families of transcription factors have been reported. However, the molecular mechanisms that underlie these interactions remain unknown, and models derived from transient-transfection experiments are contradictory. We have investigated the effect of the purified glucocorticoid receptor (GR) DNA-binding domain (GR residues 440 to 533 [GR440-533]) on DNA binding and transcription activation by Fos-Jun heterodimers and Jun homodimers. GR440-533 differentially inhibited DNA binding and transcription activation by Fos-Jun heterodimers. Inhibition of Jun homodimers required a 10-fold-higher concentration of GR440-533. An excess of Fos monomers protected Fos-Jun heterodimers from inhibition by GR440-533. Surprisingly, regions outside the leucine zipper and basic region were required for GR inhibition of Fos and Jun DNA binding. The region of GR440-533 required for inhibition of Fos-Jun DNA binding was localized to the zinc finger DNA-binding domain. However, inhibition of Fos-Jun DNA binding was independent of DNA binding by GR440-533. GR440-533 also differentially inhibited Fos-Jun heterodimer binding to the proliferin plfG element. Differential inhibition of DNA binding by different AP-1 family complexes provides a potential mechanism for the diverse interactions between nuclear hormone receptors and AP-1 family proteins at different promoters and in different cell types.
Roxithromycin. An update of its antimicrobial activity, pharmacokinetic properties and therapeutic use.

Roxithromycin is a derivative of the macrolide antibacterial erythromycin with in vitro antibacterial activity resembling that of the parent compound. The drug has activity against some Staphylococcus spp. , many Streptococcus spp. , Moraxella (Branhamella) catarrhalis, Mycoplasma pneumoniae, Legionella pneumophila and Chlamydia trachomatis as well as many less common organisms. Measured using recently proposed guidelines, roxithromycin has in vitro activity against Haemophilus influenzae. In comparison with that of its parent compound, the pharmacokinetic profile of roxithromycin is characterised by high plasma, tissue and body fluid concentrations and a long half-life permitting an extended dosage interval. Roxithromycin has proven clinical efficacy in upper and lower respiratory infections, skin and soft tissue infections, urogenital infections and orodental infections, and appears to be as effective as more established treatments including erythromycin, amoxicillin/clavulanic acid and cefaclor. The drug has also shown promise in a variety of more specialised indications including opportunistic infections in human immunodeficiency virus (HIV)-positive patients and as part of a Helicobacter pylori eradication regimen. Roxithromycin is very well tolerated with an overall incidence of adverse events of approximately 4%. Thus, roxithromycin is an attractive therapeutic alternative in its established indications, especially when the option of once-daily administration is considered.