Miracle-dz/UniFAR-FTUs huggingface dataset:
SYNTHESIS AND OPTIMIZATION OF SUBMARINE PIPELINE ROUTES

Traditionally, the selection of a pipeline route for offshore applications has been manually performed by the engineer, by a quick inspection of the seabottom bathymetry and the available information regarding obstacles. Eventually the evaluation of a given route could be performed using analysis tools, but in any case the process is highly dependent on the expertise of the engineer. In this context, this work describes the development of a compu- tational tool for the synthesis and optimization of submarine pipeline routes, using computa- tional tools based in Evolutionary Algorithms. In such optimization procedures, each candidate route is randomly generated and is evaluat- ed, in order to determine its "fitness", in terms of several criteria that are incorporated in an objective function. Such function takes into account all relevant aspects that should be con- sidered in the selection of a route, such as total pipeline length; geophysical and geotech- nical data obtained from the bathymetry and sonography, including the definition of obstacles and regions that should be avoided; number, length and location of free spans to be mitigated along the routes. Other aspects depend on the structural behavior of the pipe, under hydro- static and environmental loadings; some of these aspects are dealt with by following recom- mendations established in the DNV RP-F105 and RP-F109 codes, related respectively to the on-bottom stability and free spans. This work describes the implementation of the optimization tool, beginning with the assembly of the objective function and the definition of the problem constraints, and proceeding with the association of this function and constraints in the framework of the implementation of a Genetic Algorithm - GA. Case studies are presented to illustrate the use of this optimization tool. It is expected that the application of such tool may reduce the design time needed to as- sess an optimal pipeline route, while reducing computational overheads and providing more accurate results (avoiding mistakes with route interpretation), ultimately minimizing costs with respect to submarine pipeline design and installation.
Stimulation of Glucose Uptake by the Natural Coenzyme α-Lipoic Acid/Thioctic Acid: Participation of Elements of the Insulin Signaling Pathway

Thioctic acid (α-lipoic acid), a natural cofactor in dehydrogenase complexes, is used in Germany in the treatment of symptoms of diabetic neuropathy. Thioctic acid improves insulin-responsive glucose utilization in rat muscle preparations and during insulin clamp studies performed in diabetic individuals. The aim of this study was to determine the direct effect of thioctic acid on glucose uptake and glucose transporters. In L6 muscle cells and 3T3-L1 adipocytes in culture, glucose uptake was rapidly increased by (R)-thioctic acid. The increment was higher than that elicited by the (S)-isomer or the racemic mixture and was comparable with that caused by insulin. In parallel to insulin action, the stimulation of glucose uptake by thioctic acid was abolished by wortmannin, an inhibitor of phosphatidylinositol 3-kinase, in both cell lines. Thioctic acid provoked an upward shift of the glucose-uptake insulin dose-response curve. The molar content of GLUT1 and GLUT4 transporters was measured in both cell lines. 3T3-L1 adipocytes were shown to have >10 times more glucose transporters but similar ratios of GLUT4:GLUT1 than L6 myotubes. The effect of (R)-thioctic acid on glucose transporters was studied in the L6 myotubes. Its stimulatory effect on glucose uptake was associated with an intracellular redistribution of GLUT1 and GLUT4 glucose transporters, similar to that caused by insulin, with minimal effects on GLUT3 transporters. In conclusion, thioctic acid stimulates basal glucose transport and has a positive effect on insulin-stimulated glucose uptake. The stimulatory effect is dependent on phosphatidylinositol 3-kinase activity and may be explained by a redistribution of glucose transporters. This is evidence that a physiologically relevant compound can stimulate glucose transport via the insulin signaling pathway.
Mild Oxidative Damage in the Diabetic Rat Heart Is Attenuated by Glyoxalase-1 Overexpression

Diabetes significantly increases the risk of heart failure. The increase in advanced glycation endproducts (AGEs) and oxidative stress have been associated with diabetic cardiomyopathy. We recently demonstrated that there is a direct link between AGEs and oxidative stress. Therefore, the aim of the current study was to investigate if a reduction of AGEs by overexpression of the glycation precursor detoxifying enzyme glyoxalase-I (GLO-I) can prevent diabetes-induced oxidative damage, inflammation and fibrosis in the heart. Diabetes was induced in wild-type and GLO-I transgenic rats by streptozotocin. After 24-weeks of diabetes, cardiac function was monitored with ultrasound under isoflurane anesthesia. Blood was drawn and heart tissue was collected for further analysis. Analysis with UPLC-MSMS showed that the AGE Nɛ-(1-carboxymethyl)lysine and its precursor 3-deoxyglucosone were significantly elevated in the diabetic hearts. Markers of oxidative damage, inflammation, and fibrosis were mildly up-regulated in the heart of the diabetic rats and were attenuated by GLO-I overexpression. In this model of diabetes, these processes were not accompanied by significant changes in systolic heart function, i.e., stroke volume, fractional shortening and ejection fraction. This study shows that 24-weeks of diabetes in rats induce early signs of mild cardiac alterations as indicated by an increase of oxidative stress, inflammation and fibrosis which are mediated, at least partially, by glycation.
Stellar models with microscopic diffusion and rotational mixing 1.: Application to the Sun

The Yale stellar evolution code has been modified to include the combined effects of diffusion and rotational mixing on H-1, H-4, and the trace elements He, Li-6, Li-7, and Be-9. The interaction between rotational mixing and diffusion is studied by calculating a number of calibrated solar models. The rotational mixing inhibits the diffusion in the outer parts of the models, leading to a decrease in the envelope diffusion by 25%-50%. Conversely, diffusion leads to gradients in mean molecular weight which can inhibit the rotational mixing. The degree to which gradients in mean molecular weight inhibit the rotational mixing is somewhat uncertain. A comparison with the observed solar oblateness suggests that gradients in the mean molecular weight play a smaller role in inhibiting the rotational mixing than previously believed. This is reinforced by the fact that the model with the standard value for the inhibiting effect of mean molecular weight on the rotational mixing depletes no Li on the main sequence. This is clear in contrast to the observations. A reduction in the inhibiting effect of mean molecular weight gradients by a factor of 10 loads to noticeable main-sequence Li depletion.
Pathways for the regulation of interferon‐γ‐inducible genes by iron in human monocytic cells

To elucidate iron‐regulated interferon‐γ (IFN‐γ) effector functions, we investigated three IFN‐γ‐inducible genes [intercellular adhesion molecule‐1 (ICAM‐1), human leukocyte antigen (HLA)‐DR, guanosine 5′‐triphosphate‐cyclohydrolase I (GTP‐CH)] in primary human monocytes and the cell line THP‐1. IFN‐γ increased the surface expression of ICAM‐1 and HLA‐DR and stimulated GTP‐CH activity. Addition of iron before cytokine stimulation resulted in a dose‐dependent reduction of these pathways, and iron restriction by desferrioxamine (DFO) enhanced ICAM‐1, HLA‐DR, and GTP‐CH expression. Iron neither affected IFN‐γ binding to its receptor nor IFN‐γ receptor surface expression. IFN‐γ‐inducible mRNA expression of ICAM‐1, HLA‐DR, and GTP‐CH was reduced by iron and increased by DFO by a transcriptional mechanism. Moreover, ICAM‐1 and to a lesser extent, GTP‐CH and HLA‐DR mRNA expression were regulated post‐transcriptionally, as iron pretreatment resulted in shortening the mRNA half‐life compared with cells treated with IFN‐γ alone. Thus, iron perturbations regulate IFN‐γ effector pathways by transcriptional and post‐transcriptional mechanisms, indicating that iron rather interferes with IFN‐γ signal‐transduction processes.
Ofatumumab added to dexamethasone in patients with relapsed or refractory chronic lymphocytic leukemia: Results from a phase II study

The treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) remains a challenging clinical issue. An important treatment option is the use of high‐dose corticosteroids. The purpose of this clinical trial was to determine the efficacy and toxicity of an ofatumumab–dexamethasone (O‐Dex) combination in relapsed or refractory CLL. The trial was an open‐label, multicenter, nonrandomized, Phase II study. The O‐Dex regimen consisted of intravenous ofatumumab (Cycle 1: 300 mg on day 1, 2,000 mg on days 8, 15, and 22; Cycles 2–6: 1,000 mg on days 1, 8, 15, and 22) and oral dexamethasone (40 mg on days 1–4 and 15–18; Cycles 1–6). The O‐Dex regimen was given until best response, or a maximum of six cycles. Thirty‐three patients (pts) were recruited. Twenty‐four (73%) pts completed at least three cycles of therapy. The remaining nine pts were prematurely discontinued owing to Grade 3/4 infections (seven pts), disease progression (one pt), or uncontrollable diabetes mellitus (one pt). Overall response rates/complete remissions (ORR/CR) were achieved in 22/5 pts (67/15%). The median progression‐free survival (PFS) was 10 months. In pts with p53 defects (n = 8), ORR/CR were achieved in 5/2 pts (63/25%) with a median PFS of 10.5 months. The median overall survival (OS) was 34 months. The Grades 3–5 infectious toxicity in 33% of pts represented the most frequent side effect during the treatment period. In conclusion, the O‐Dex regimen shows a relatively high ORR and CR with promising findings for PFS and OS. The study was registered at www.clinicaltrials. gov (NCT01310101). Am. J. Hematol. 90:417–421, 2015. © 2015 Wiley Periodicals, Inc.
Realized Variance and IID Market Microstructure Noise

We analyze the properties of a bias-corrected realized variance (RV) in the presence of iid market microstructure noise. The bias correction is based on the first-order autocorrelation of intraday returns and we derive the optimal sampling frequency as defined by the mean squared error (MSE) criterion. The bias-corrected RV is benchmarked to the standard measure of RV and an empirical analysis shows that the former can reduce the MSE by 50%-90%. Our empirical analysis also shows that the iid noise assumption does not hold in practice. While this need not affect the RVs that are based on low-frequency intraday returns, it has important implications for those based on high-frequency returns
Title : In vitro study of the anti-cancer effects of artemisone alone or in combination with other chemotherapeutic agents Authors :

Affiliation: Department of Oncology, Division of Cellular and Molecular Medicine, St George’s, University of London, UK. Centre for Infection, Division of Cellular and Molecular Medicine, St George’s, University of London, UK. Department of Chemistry, Open Laboratory of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (PR China)
Outage probability of LMMSE receiver in multipath Nakagami-m fading channels

We investigate the outage probability of a multiuser receiver in fading channels. We focus on the multipath, Nakagami-m channels with arbitrary m and path powers. Approximate analytical expressions of the outage probability of the linear minimum mean-squared error (LMMSE) receiver are derived when the receiver employs the channel gain variances of the interferers. In deriving the analytical expressions, we exploit large system analysis and the gamma series representation of the probability density function (PDF) of a sum of independent gamma variables. The outage probability is evaluated under a range of receiver implementations. The accuracy of the theoretical results is examined through simulation.
Motivation Measures in Sport: A Critical Review and Bibliometric Analysis

Motivation is widely-researched, in both sport psychology and other fields. As rigorous measurement is essential to understanding this latent construct, a critical appraisal of measurement instruments is needed. Thus, the purpose of this review was to evaluate the six most highly cited motivation measures in sport. Peer-reviewed articles published prior to August 2016 were searched to identify the six most highly cited motivation questionnaires in sport: Sport Motivation Scale (SMS), Intrinsic Motivation Inventory (IMI), Situational Motivational Scale (SIMS), Perceptions of Success Questionnaire (POSQ), Behavioural Regulation in Sport Questionnaire (BRSQ), and Task and Ego Orientation in Sport Questionnaire (TEOSQ). The questionnaires were then evaluated and discussed in four sections: Development, Reliability, Correlates, and Summary. Bibliometric data were also calculated (average weighted impact factor) and assessed (e.g., citations per year) to evaluate the impact of the use of each questionnaire. Despite some variance in their psychometric properties, conceptualization, structure, and utility, the six questionnaires are psychometrically strong instruments for quantifying motivation that are widely supported in the literature. Bibliometric analyses suggested that the IMI ranks first and the SMS ranks sixth according to the average weighted impact factors of their original publications. Consideration of each questionnaire's psychometric strengths/limitations, and conceptualization of motivation in the context of specific research questions should guide researchers in selecting the most appropriate instrument to measure motivation in sport. The average weighted impact factor of each questionnaire is a useful value to consider as well. With these points in mind, recommendations are provided.
Information Acquisition and Welfare LUCA COLOMBO

We study information acquisition in a flexible framework with strategic complementarity or substitutability in actions and a rich set of externalities that are responsible for possible wedges between the equilibrium and the efficient acquisition of information. First, we relate the (in)efficiency in the acquisition of information to the (in)efficiency in the use of information and explain why efficiency in the use is no guarantee of efficiency in the acquisition. Next, we show how the acquisition of private information affects the social value of public information (i.e. the comparative statics of equilibrium welfare with respect to the quality of public information). Finally, we illustrate the implications of the results in a monetary economy with price rigidities and dispersed information about productivity shocks.
Veterinary Immunology and Immunopathology Maternal Antibody Uptake, Duration and Influence on Survival and Growth Rate in a Cohort of Indigenous Calves in a Smallholder Farming System in Western Kenya

The passive transfer of antibodies from dams to offspring via colostrum is believed to play an important role in protecting neonatal mammals from infectious disease. The study presented here investigates the uptake of colostrum by 548 calves in western Kenya maintained under smallholder farming, an important agricultural system in eastern Africa. Serum samples collected from the calves and dams at recruitment (within the first week of life) were analysed for the presence of antibodies to four tick-borne haemoparasites: Anaplasma marginale, Babesia bigemina, Theileria mutans and Theileria parva. The analysis showed that at least 89.33% of dams were seropositive for at least one of the parasites, and that 93.08% of calves for which unequivocal results were available showed evidence of having received colostrum. The maternal antibody was detected up until 21 weeks of age in the calves. Surprisingly, there was no discernible difference in mortality or growth rate between calves that had taken colostrum and those that had not. The results are also important for interpretation of serosurveys of young calves following natural infection or vaccination.
Bio process control strategy based on numerical methods and linear algebra: second approach

Biotechnological processes represent a challenge into the control field, due to its high non linearity. Particularly, continuous alcoholic fermentation by Zymomonas mobilis presents high ethanol performance, but it shows highly oscillatory behaviour in process variables, because of the influence of inhibition dynamics (rate of ethanol concentration Z and I) over Biomass, Substrate and Product concentrations; it is a significant challenge from the control perspective. In this work, a new and significant solution for control of biotechnological variables into the fermentation process, based on numerical methods and linear algebra is proposed. This methodology, allows developing the controller design through the use of dynamic analysis and without the use of complex calculations.
Autoregulation of swrAA and Motility in Bacillus subtilis

ABSTRACT We demonstrate that transcription of the gene swrAA, required for swarming migration in Bacillus subtilis, is driven by two promoters: a sigD-dependent promoter and a putative sigA-dependent promoter, which is inactive during growth in liquid Luria-Bertani medium and becomes active in the presence of the phosphorylated form of the response regulator DegU or on semisolid surfaces. Since sigD transcription is enhanced by SwrAA, this finding reveals that swrA expression is controlled by a positive feedback loop. We also demonstrate that the positive action of SwrAA in swimming and swarming motility is prevented in strains carrying a deletion of the two-component system degS-degU and that this effect is independent of swrAA transcription. Therefore, both DegU and SwrAA must be present to achieve full motility in B. subtilis.
Disease activity and pretreatment, rather than hypogammaglobulinaemia, are major risk factors for infectious complications in patients with chronic lymphocytic leukaemia

Summary. To identify patients at high risk of life‐threatening infections, we retrospectively analysed the prevalence of infectious complications in 187 chronic lymphocytic leukaemia patients treated in our institution since 1999 and correlated them with clinical features. A questionnaire with detailed questions regarding infectious complications was mailed to patients and their general practitioners. Major infections (requiring intravenous antibiotics or inpatient treatment) were reported in 37 patients (19·8%) and minor infections (requiring oral antibiotics and outpatient treatment) in 113 patients (60·4%). Univariate analysis identified advanced disease (P = 0·02), gender (P = 0·01), duration of disease (P = 0·007), number of previous chemotherapy regimens (P < 0·001), previous therapy with purine analogues and monoclonal antibodies (P < 0·001; P = 0·019), massive splenomegaly (P = 0·03), low granulocyte count (P < 0·001), low serum immunoglobulin concentration (P = 0·005), low haemoglobin concentration (P < 0·001) and high serum lactate dehydrogenase (LDH) concentration (P < 0·001) as risk factors for major infections. In multivariable logistic regression analysis, only the number of previous chemotherapy regimens (risk ratio [RR] = 1·8; 95% confidence interval [CI] 1·2–8·0) and haemoglobin concentration (RR = 0·6; CI 0·5–0·8) remained significant for major infections. The number of previous chemotherapy regimens was the only independent risk factor for minor (RR = 7·6; CI 2·2–25·7) and varicella‐zoster virus infections (RR = 2·1; CI 1·3–3·4). In untreated patients, the only risk factor for major infections was LDH concentration. Patients treated with purine analogues or autologous stem cell transplantation had a higher risk of developing viral infections. In conclusion, disease activity and pretreatment extent have a stronger impact on the risk of severe infectious complications than hypogammaglobulinaemia. Preferably, prophylactic strategies should be evaluated in patients defined by these parameters.
Exquisite sensitivity to subsecond, picomolar nitric oxide transients conferred on cells by guanylyl cyclase-coupled receptors

Nitric oxide (NO) functions as a diffusible transmitter in most tissues of the body and exerts its effects by binding to receptors harboring a guanylyl cyclase transduction domain, resulting in cGMP accumulation in target cells. Despite its widespread importance, very little is known about how this signaling pathway operates at physiological NO concentrations and in real time. To address these deficiencies, we have exploited the properties of a novel cGMP biosensor, named δ-FlincG, expressed in cells containing varying mixtures of NO-activated guanylyl cyclase and cGMP-hydrolyzing phosphodiesterase activity. Responsiveness to NO, signifying a physiologically relevant rise in cGMP to 30 nM or more, was seen at concentrations as low as 1 pM, making cells by far the most sensitive NO detectors yet encountered. Even cells coexpressing phosphodiesterase-5, a cGMP-activated isoform found in many NO target cells, responded to NO in concentrations as low as 10 pM. The dynamics of NO capture and signal transduction was revealed by administering timed puffs of NO from a local pipette. A puff lasting only 100 ms, giving a calculated peak intracellular NO concentration of 23 pM, was detectable. The results could be encapsulated in a quantitative model of cellular NO-cGMP signaling, which recapitulates the NO responsiveness reported previously from crude cGMP measurements on native cells, and which explains how NO is able to exert physiological effects at extremely low concentrations, when only a tiny proportion of its receptors would be occupied.
Gene Evolutionary Trajectories and GC Patterns Driven by Recombination in Zea mays

Recombination occurring during meiosis is critical for creating genetic variation and plays an essential role in plant evolution. In addition to creating novel gene combinations, recombination can affect genome structure through altering GC patterns. In maize (Zea mays) and other grasses, another intriguing GC pattern exists. Maize genes show a bimodal GC content distribution that has been attributed to nucleotide bias in the third, or wobble, position of the codon. Recombination may be an underlying driving force given that recombination sites are often associated with high GC content. Here we explore the relationship between recombination and genomic GC patterns by comparing GC gene content at each of the three codon positions (GC1, GC2, and GC3, collectively termed GCx) to instances of a variable GC-rich motif that underlies double strand break (DSB) hotspots and to meiocyte-specific gene expression. Surprisingly, GCx bimodality in maize cannot be fully explained by the codon wobble hypothesis. High GCx genes show a strong overlap with the DSB hotspot motif, possibly providing a mechanism for the high evolutionary rates seen in these genes. On the other hand, genes that are turned on in meiosis (early prophase I) are biased against both high GCx genes and genes with the DSB hotspot motif, possibly allowing important meiotic genes to avoid DSBs. Our data suggests a strong link between the GC-rich motif underlying DSB hotspots and high GCx genes.