Miracle-dz/UniFAR-FTUs huggingface dataset:
Cirrus clouds triggered by radiation, a multiscale phenomenon

Abstract. In this study, the influence of radiative cooling and small eddies on cirrus formation is investigated. For this purpose the non-hydrostatic, anelastic model EULAG is used with a recently developed and validated ice microphysics scheme (Spichtinger and Gierens, 2009a). Additionally, we implemented a fast radiative transfer code (Fu et al., 1998). Using idealized profiles with high ice supersaturations up to 144% and weakly stable stratifications with Brunt-Vaisala frequencies down to 0.0018 s−1 within a supersaturated layer, the influence of radiation on the formation of cirrus clouds is remarkable. Due to the radiative cooling at the top of the ice supersaturated layer with cooling rates down to −3.5 K/d, the stability inside the ice supersaturated layer decreases with time. During destabilization, small eddies induced by Gaussian temperature fluctuations start to grow and trigger first nucleation. These first nucleation events then induce the growth of convective cells due to the radiative destabilization. The effects of increasing the local relative humidity by cooling due to radiation and adiabatic lifting lead to the formation of a cirrus cloud with IWC up to 33 mg/m3 and mean optical depths up to 0.36. In a more stable environment, radiative cooling is not strong enough to destabilize the supersaturated layer within 8 h; no nucleation occurs in this case. Overall triggering of cirrus clouds via radiation works only if the supersaturated layer is destabilized by radiative cooling such that small eddies can grow in amplitude and finally initialize ice nucleation. Both processes on different scales, small-scale eddies and large-scale radiative cooling are necessary.
Screening instruments for predicting return to work in long-term sickness absence.

Background Multiple somatic symptoms are common and may cause prolonged sickness absence (SA) and unsuccessful return to work (RTW). Aims To compare three instruments and their predictive and discriminative abilities regarding RTW. Methods A longitudinal cohort study of participants recruited from two municipal job centres, with at least 8 weeks of SA. The instruments used were the Symptom Check List of somatic distress (SCL-SOM) (score 0-48 points), the Bodily Distress Syndrome Questionnaire (BDSQ) (0-120 points) and the one-item self-rated health (SRH) (1-5 points). The instruments' predictive value was explored in a time-to-event analysis. Different cut-points were analysed to find the highest number of correctly classified RTW cases, identified in a register on public transfer payments. Results The study involved 305 subjects. The adjusted relative risk regarding prediction of RTW was 0.89 [95% confidence interval (CI) 0.83-0.95], 0.89 (95% CI 0.83-0.95) and 0.78 (95% CI 0.70-0.86) per 5-, 10- and 1-point increase in the SCL-SOM, BDSQ and SRH, respectively. After mutual adjustment for the three instruments, only the prediction of RTW from SRH remained statistically significant 0.81 (95% CI 0.72-0.92). The highest sensitivity (86%) was found by SRH at the cut-point ≤5, at which 62% were correctly classified. Conclusions All three instruments predicted RTW, but only SRH remained a significant predictor after adjustment for the SCL-SOM and BDSQ. The SRH provides an efficient alternative to more time-consuming instruments such as SCL-SOM or BDSQ for estimating the chances of RTW among sickness absentees.
mTOR Complexes Repress Hypertrophic Agonist–Stimulated Expression of Connective Tissue Growth Factor in Adult Cardiac Muscle Cells

Abstract: Connective tissue growth factor (CTGF) is a fibrogenic cytokine that promotes fibrosis in various organs. In the heart, both cardiomyocytes (CM) and cardiac fibroblasts have been reported as a source of CTGF expression, aiding cardiac fibrosis. Although the mammalian target of rapamycin (mTOR) forms 2 distinct complexes, mTORC1 and mTORC2, and plays a central role in integrating biochemical signals for protein synthesis and cellular homeostasis, we explored its role in CTGF expression in adult feline CM. CM were stimulated with 10 &mgr;M phenylephrine (PE), 200 nM angiotensin (Ang), or 100 nM insulin for 24 hours. PE and Ang, but not insulin, caused an increase in CTGF mRNA expression with the highest expression observed with PE. Inhibition of mTOR with torin1 but not rapamycin significantly enhanced PE-stimulated CTGF expression. Furthermore, silencing of raptor and rictor using shRNA adenoviral vectors to suppress mTORC1 and mTORC2, respectively, or blocking phosphatidylinositol 3-kinase (PI3K) signaling with LY294002 (LY) or Akt signaling by dominant-negative Akt expression caused a substantial increase in PE-stimulated CTGF expression as measured by both mRNA and secreted protein levels. However, studies with dominant-negative delta isoform of protein kinase C demonstrate that delta isoform of protein kinase C is required for both agonist-induced CTGF expression and mTORC2/Akt-mediated CTGF suppression. Finally, PE-stimulated CTGF expression was accompanied with a corresponding increase in Smad3 phosphorylation and pretreatment of cells with SIS3, a Smad3 specific inhibitor, partially blocked the PE-stimulated CTGF expression. Therefore, a PI3K/mTOR/Akt axis plays a suppressive role on agonist-stimulated CTGF expression where the loss of this mechanism could be a contributing factor for the onset of cardiac fibrosis in the hypertrophying myocardium.
A cost-minimization analysis of large overjet reduction with two removable functional appliances based on a randomized controlled trial

Objective The purpose of this study was to assess and relate the societal costs of reducing large overjet with a prefabricated functional appliance (PFA), or a slightly modified Andresen activator (AA), using a cost-minimization analysis (CMA). Design, settings, and participants A multicentre, prospective, randomized clinical trial was conducted with patients from 12 general dental practices. Ninety-seven patients with an Angle Class II, division 1 malocclusion, and an overjet of ≥6 mm were randomly allocated by lottery to treatment with either a PFA or an AA. The PFA and AA groups consisted of 57 and 40 subjects, respectively. Blinding was not performed. Duration of treatment, number of scheduled/unscheduled appointments, and retreatment were registered. Direct and indirect costs were analysed with reference to intention-to-treat (ITT), successful (S), and unsuccessful (US) outcomes. Societal costs were described as the total of direct and indirect costs, not including retreatments. Interventions Treatment with a PFA or an AA. Results The direct and societal costs were significantly lower for the PFA than for the AA group. The number of visits was lower in the PFA group, when ITT was considered, and for the US cases as well. No difference in retreatment rate could be seen between the groups. Limitations Costs depend on local factors and thus should not be generalized to other settings. Harms No harms were detected during the study. Conclusion The success rate of the both appliances was low. However, the PFA was the preferred approach for reduction of a large overjet in mixed dentition, since it minimized costs and there were no difference in clinical outcomes between PFA and AA. Registration This trial was registered at 'FoU i Sverige' (http://www.fou.nu/is/sverige), registration number: 97131. Protocol The protocol was not published before trial commencement.
The Drosophila simulans Y chromosome interacts with the autosomes to influence male fitness

The Y chromosome should degenerate because it cannot recombine. However, male‐limited transmission increases selection efficiency for male‐benefit alleles on the Y, and therefore, Y chromosomes should contribute significantly to variation in male fitness. This means that although the Drosophila Y chromosome is small and gene‐poor, Y‐linked genes are vital for male fertility in Drosophila melanogaster and the Y chromosome has large male fitness effects. It is unclear whether the same pattern is seen in the closely related Drosophila simulans. We backcrossed Y chromosomes from three geographic locations into five genetic backgrounds and found strong Y and genetic background effects on male fertility. There was a significant Y‐background interaction, indicating substantial epistasis between the Y and autosomal genes affecting male fertility. This supports accumulating evidence that interactions between the Y chromosome and the autosomes are key determinants of male fitness.
Role of Prefrontal Serotonergic and Dopaminergic Systems in Encounter-Induced Hyperactivity in Methamphetamine-Sensitized Mice

Abstract Background: Isolation-reared mice show social encounter-induced hyperactivity with activation of prefrontal serotonergic and dopaminergic systems, but it is not known whether this stress response is observed in other pathological conditions. Here we examined whether the social encounter stimulation induces abnormal behavior during withdrawal in chronic methamphetamine-treated mice. Methods: To induce methamphetamine-induced behavioral sensitization, male mice were injected with methamphetamine (1 mg/kg) once daily for 7 days. Results: The encounter with an intruder elicited hyperactivity 24 h after the last injection of methamphetamine in methamphetamine-sensitized mice. This response was observed even as long as 2 weeks after withdrawal of methamphetamine. The encounter increased c-Fos expression in the prefrontal cortex, dorsal raphe nucleus and ventral tegmental area in methamphetamine-sensitized mice, while it did not in control mice. Furthermore, the encounter increased extracellular serotonin (5-HT) and dopamine, but not noradrenaline, levels in the prefrontal cortex in methamphetamine-sensitized mice. Local injection of 5,7-dihydroxytryptamine and 6-hydroxydopamine into the prefrontal cortex attenuated encounter-induced hyperactivity in methamphetamine-sensitized mice and it markedly decreased prefrontal 5-HT and dopamine levels, respectively. Pharmacological analysis showed that the encounter-induced hyperactivity is mediated by dopamine D1 receptors and 5-HT2A receptors and attenuated by anxiolytics and antidepressants such as diazepam, osemozotan and selective 5-HT reuptake inhibitors. The effect of paroxetine was blocked by the 5-HT3 receptor antagonist azasetron. Conclusions: The present study shows that psychological stress elicits hyperactivity with activation of prefrontal 5-HT and dopamine systems in methamphetamine-dependent mice and suggests that the abnormal behavior is associated with anxiety and depression.
Clinical significance of slightly lateral ventricular enlargement in healthy infants

Abstract Objective: The aim of this study was to determine the clinical significance of slightly lateral ventricular enlargement. Methods: We examined 1151 infants with a gestational age of 36 weeks or greater. We assessed for the presence of ventricular enlargement when apparent space was observed in the frontal horn or body of lateral ventricle by a transfontanel ultrasound scan. Results: Two hundred and forty-eight infants had ventricular enlargement. The atrial widths in most infants were less than 10 mm. Ventricular enlargement correlated with Cesarean delivery, gestational age, birth weight, respiratory disturbance at delivery and respiratory inhibition after crying (RIAC). Ventricular enlargement could be divided into three types by ultrasound findings. Forty-five infants showed only enlargement of the anterior horn (Type A), 97 infants showed enlargement from the body to the posterior horn (Type B), and 108 infants showed whole enlargement from the anterior to the posterior horn (Type C). The infants with Type A correlated with intrauterine growth restriction, placenta previa, male gender and birth weight. The infants with Type B correlated with cesarean delivery. The infants with Type C correlated with diabetes mellitus, respiratory disturbance at delivery, RIAC and feeding hypoxemia. Conclusions: Slightly lateral ventricular enlargement should be considered clinically significant.
Iron oxide magnetic nanoparticles as antimicrobials for therapeutics

Abstract The use of iron oxide magnetic nanoparticles (IMNP) in medical and pharmaceutical areas dates to the beginning of the 1970s, as carriers. Some other uses to these nanoparticles are in vitro separation, magnetic resonance imaging and drug targeting agent. Many preparations containing IMNP have been described and used in drug delivery, hyperthermia, in vitro separation, tissue repair, cellular therapy, for magnetic separation, magnetic resonance imaging, as spoilers for magnetic resonance spectroscopy, and more recently as sensors for metabolites and other biomolecules. The use of these nanostructures as antibacterial agents has also been reported, which could kill some bacteria species causing no damage to the human host cells. Recently, they have been used as hyperthermia agents to treat infections or cancer, which are more susceptible than the healthy host’s cells. Engineering designs, physiochemical characteristics, biomedical applications of IMNP, toxicity and magnetic nanotoxicology have been discussed. However, the application of IMNP as antimicrobials is very important. Thus, this review explores the therapeutic activities of IMNP and their use as antimicrobial agents. These nanoparticles can be efficient for the treatment of microbial infections, probably acting as membrane permeability enhancer, damaging the cell wall or by generating reactive oxygen species.
Serotonylation of Vascular Proteins Important to Contraction

Background Serotonin (5-hydroxytryptamine, 5-HT) was named for its source (sero-) and ability to modify smooth muscle tone (tonin). The biological effects of 5-HT are believed to be carried out by stimulation of serotonin receptors at the plasma membrane. Serotonin has recently been shown to be synthesized in vascular smooth muscle and taken up from external sources, placing 5-HT inside the cell. The enzyme transglutaminase uses primary amines such as 5-HT to covalently modify proteins on glutamine residues. We tested the hypothesis that 5-HT is a substrate for transglutaminase in arterial vascular smooth muscle, with protein serotonylation having physiological function. Methodology/Principal Findings The model was the rat aorta and cultured aortic smooth muscle cells. Western analysis demonstrated that transglutaminase II was present in vascular tissue, and transglutaminase activity was observed as a cystamine-inhibitable incorporation of the free amine pentylamine-biotin into arterial proteins. Serotonin-biotin was incorporated into α -actin, β-actin, γ-actin, myosin heavy chain and filamin A as shown through tandem mass spectrometry. Using antibodies directed against biotin or 5-HT, immunoprecipitation and immunocytochemistry confirmed serotonylation of smooth muscle α–actin. Importantly, the α-actin-dependent process of arterial isometric contraction to 5-HT was reduced by cystamine. Conclusions 5-HT covalently modifies proteins integral to contractility and the cytoskeleton. These findings suggest new mechanisms of action for 5-HT in vascular smooth muscle and consideration for intracellular effects of primary amines.
fCCAC: functional canonical correlation analysis to evaluate covariance between nucleic acid sequencing datasets

Summary Computational evaluation of variability across DNA or RNA sequencing datasets is a crucial step in genomic science, as it allows both to evaluate the reproducibility across biological or technical replicates, and to compare different datasets to identify their potential correlations. Here I present fCCAC, an application of functional canonical correlation analysis to assess covariance of nucleic acid sequencing datasets such as chromatin immunoprecipitation followed by deep sequencing (ChIP-seq). I exemplify how this method can reveal shared covariance between histone modifications and DNA binding proteins, such as the relationship between the H3K4me3 chromatin mark and its epigenetic writers and readers. Availability R code is publicly available at http://github.com/pmb59/fCCAC/. Contact pm12@sanger.ac. uk
Cement mortars and geopolymers with the same strength class

Recycling of industrial waste materials to manufacture environmentally friendly mortars and concretes is gaining more and more interest, in particular for sustainability, rehabilitation and renovation purposes. In the present study geopolymers, which had been made using fly ash as a precursor and were subsequently subjected to curing at room temperature, were investigated. Geopolymeric and cementitious mortars with the same mechanical strength class were compared in both the fresh and hardened states. Despite the higher free shrinkage and lower adhesive strength on brick substrate, geopolymeric mortars behaved better than cement types in terms of lower dynamic modulus of elasticity, higher water vapour permeability, lower capillary water absorption and higher resistance to salt crystallisation.
Hardware-Accelerated Memory Operations on Large-Scale NUMA Systems

As NUMA systems grow in complexity, the average distance of memory increases. Because the number of parallel read requests is limited, this reduces the bandwidth available to the CPUs. Also, the cost of cache coherency increases as atomic operations are synced across multiple hops. We explore how these problems can be alleviated by offloading NUMA accesses to the interconnect hardware and show how databases can profit. For cross-NUMA table scans, we report a performance improvement of up to 30%; for atomic increments as used for transaction sequencing up to 10x, and for latches up to 8x. These experiments were performed on an SGI UV300 system but demonstrate the general value of explicit memory instructions.
Multiple and asymmetrical origin of polyploid dog rose hybrids (Rosa L. sect. Caninae (DC.) Ser.) involving unreduced gametes

Background and Aims Polyploidy and hybridization are important factors for generating diversity in plants. The species-rich dog roses ( Rosa sect. Caninae ) originated by allopolyploidy and are characterized by unbalanced meiosis producing polyploid egg cells (usually 4 x ) and haploid sperm cells (1 x ). In extant natural stands species hybridize spontaneously, but the extent of natural hybridization is unknown. The aim of the study was to document the frequency of reciprocal hybridization between the subsections Rubigineae and Caninae with special reference to the contribution of unreduced egg cells (5 x ) producing 6 x offspring after fertilization with reduced (1 x ) sperm cells. We tested whether hybrids arose by independent multiple events or via a single or few incidences followed by a subsequent spread of hybrids. Methods Population genetics of 45 mixed stands of dog roses across central and south-eastern Europe were analysed using microsatellite markers and flow cytometry. Hybrids were recognized by the presence of diagnostic alleles and multivariate statistics were used to display the relationships between parental species and hybrids. Key Results Among plants classified to subsect. Rubigineae , 32 % hybridogenic individuals were detected but only 8 % hybrids were found in plants assigned to subsect. Caninae . This bias between reciprocal crossings was accompanied by a higher ploidy level in Rubigineae hybrids, which originated more frequently by unreduced egg cells. Genetic patterns of hybrids were strongly geographically structured, supporting their independent origin. Conclusions The biased crossing barriers between subsections are explained by the facilitated production of unreduced gametes in subsect. Rubigineae . Unreduced egg cells probably provide the highly homologous chromosome sets required for correct chromosome pairing in hybrids. Furthermore, the higher frequency of Rubigineae hybrids is probably influenced by abundance effects because the plants of subsect. Caninae are much more abundant and thus provide large quantities of pollen. Hybrids are formed spontaneously, leading to highly diverse mixed stands, which are insufficiently characterized by the actual taxonomy.
Cardiac resynchronization therapy when no lateral pacing option exists: vectorcardiographic guided non-lateral left ventricular lead placement predicts acute hemodynamic response

Aims A difficult cardiac resynchronization therapy (CRT) implantation scenario emerges when no lateral pacing option exists. The aim of this study was to explore the effect of biventricular pacing (BIVP) on vectorcardiographic parameters in patients with a non-lateral left ventricular (LV) lead position. We hypothesized that perimeter and area reduction for both the QRS complex and T-wave would predict acute CRT response. Methods and results Twenty-six patients (14 ischaemic) with a mean age of 63 ± 10 years and standard CRT indication underwent device implantation with continuous LV pressure registration. The LV lead was placed in either an anterior or apical position. Biventricular pacing was performed at a rate 10% above intrinsic rhythm with acute CRT response defined as LV ΔdP/dtmax >10%. Using this criterion 12 patients were identified as acute CRT responders (responders: 16.7 ± 4.8% vs. non-responders: 1.9 ± 5.3%, P < 0.001). Vectorcardiographic assessment of the QRS complex and T-wave were performed at baseline and under BIVP. Based on the observed changes in three-dimensional area and perimeter, ΔQRS-area (responders: -46.7 ± 39.6% vs. non-responders: 1.1 ± 50.9%, P = 0.006) was considered as the preferred parameter. Receiver operating characteristic curve analysis identified -40% as the optimal cut-off value (sensitivity 67% and specificity 93%) for prediction of acute CRT response (AUC = 0.81, P < 0.01). A significant correlation was observed between LV ΔdP/dtmax and ΔQRS-area (R2 = 0.37, P = 0.001). Conclusion ΔQRS-area is correlated to LV ΔdP/dtmax and predicts acute CRT response in patients with a non-lateral LV lead position. Assessment of ΔQRS-area might be a useful tool for patient specific LV lead placement when no lateral pacing option exists.
Communicating Relative Risk Changes with Baseline Risk

Background. Treatment benefits and harms are often communicated as relative risk reductions and increases, which are frequently misunderstood by doctors and patients. One suggestion for improving understanding of such risk information is to also communicate the baseline risk. We investigated 1) whether the presentation format of the baseline risk influences understanding of relative risk changes and 2) the mediating role of people’s numeracy skills. Method. We presented laypeople (N = 1234) with a hypothetical scenario about a treatment that decreased (Experiments 1a, 2a) or increased (Experiments 1b, 2b) the risk of heart disease. Baseline risk was provided as a percentage or a frequency. In a forced-choice paradigm, the participants’ task was to judge the risk in the treatment group given the relative risk reduction (or increase) and the baseline risk. Numeracy was assessed using the Lipkus 11-item scale. Results. Communicating baseline risk in a frequency format facilitated correct understanding of a treatment’s benefits and harms, whereas a percentage format often impeded understanding. For example, many participants misinterpreted a relative risk reduction as referring to an absolute risk reduction. Participants with higher numeracy generally performed better than those with lower numeracy, but all participants benefitted from a frequency format. Limitations are that we used a hypothetical medical scenario and a nonrepresentative sample. Conclusions. Presenting baseline risk in a frequency format improves understanding of relative risk information, whereas a percentage format is likely to lead to misunderstandings. People’s numeracy skills play an important role in correctly understanding medical information. Overall, communicating treatment benefits and harms in the form of relative risk changes remains problematic, even when the baseline risk is explicitly provided.