Miracle-dz/UniFAR-FTUs huggingface dataset:
MNK Inhibition Disrupts Mesenchymal Glioma Stem Cells and Prolongs Survival in a Mouse Model of Glioblastoma

Glioblastoma multiforme remains the deadliest malignant brain tumor, with glioma stem cells (GSC) contributing to treatment resistance and tumor recurrence. We have identified MAPK-interacting kinases (MNK) as potential targets for the GSC population in glioblastoma multiforme. Isoform-level subtyping using The Cancer Genome Atlas revealed that both MNK genes (MKNK1 and MKNK2) are upregulated in mesenchymal glioblastoma multiforme as compared with other subtypes. Expression of MKNK1 is associated with increased glioma grade and correlated with the mesenchymal GSC marker, CD44, and coexpression of MKNK1 and CD44 predicts poor survival in glioblastoma multiforme. In established and patient-derived cell lines, pharmacologic MNK inhibition using LY2801653 (merestinib) inhibited phosphorylation of the eukaryotic translation initiation factor 4E, a crucial effector for MNK-induced mRNA translation in cancer cells and a marker of transformation. Importantly, merestinib inhibited growth of GSCs grown as neurospheres as determined by extreme limiting dilution analysis. When the effects of merestinib were assessed in vivo using an intracranial xenograft mouse model, improved overall survival was observed in merestinib-treated mice. Taken together, these data provide strong preclinical evidence that pharmacologic MNK inhibition targets mesenchymal glioblastoma multiforme and its GSC population. Implications: These findings raise the possibility of MNK inhibition as a viable therapeutic approach to target the mesenchymal subtype of glioblastoma multiforme. Mol Cancer Res; 14(10); 984–93. ©2016 AACR.
Adults Engaged in Sports in Early Life Have Higher Bone Mass Than Their Inactive Peers.

PURPOSE To analyze the relationship between engagement in sports in early life and bone variables among adults of both sexes. METHODS The sample was composed of 225 men and women. Demographic data were collected, and dual-energy X-ray absorptiometry was used to assess bone mineral density, bone mineral content, and lean soft tissue. Sports participation in early life was assessed by an interview including childhood and adolescence. Consumption of tobacco and alcohol was also assessed by interview and the habitual physical activity level by a pedometer. RESULTS Inactive men had bone mineral content around 11% lower than active men in childhood or adolescence, whereas for women, this difference represented around 14%. Active men had 74% less fat mass than inactive men in early life, and the difference was 67% for women. Early sports participation explained the differences in whole-body bone mineral content (16.8%, P-value = .005) and bone mineral density (8.8%, P-value = .015), as well as bone mineral density in lower limbs (18.9%, P-value = .001) among women. CONCLUSION Adults engaged in sports in early life have higher bone mass than their inactive peers, especially women.
Improved squalene production through increasing lipid contents in Saccharomyces cerevisiae

Squalene, a valuable acyclic triterpene, can be used as a chemical commodity for pharmacology, flavor, and biofuel industries. Microbial production of squalene has been of great interest due to its limited availability, and increasing prices extracted from animal and plant tissues. Here we report genetic perturbations that synergistically improve squalene production in Saccharomyces cerevisiae. As reported previously, overexpression of a truncated HMG‐CoA reductase 1 (tHMG1) led to the accumulation 20‐fold higher squalene than a parental strain. In order to further increase squalene accumulation in the tHMG1 overexpressing yeast, we introduced genetic perturbations—known to increase lipid contents in yeast—to enhance squalene accumulation as lipid body is a potential storage of squalene. Specifically, DGA1 coding for diacylglycerol acyltranferase was overexpressed to enhance lipid biosynthesis, and POX1 and PXA2 coding for acyl‐CoA oxidase and a subunit of peroxisomal ABC transporter were deleted to reduce lipid β‐oxidation. Simultaneous overexpression of tHMG1 and DGA1 coding for rate‐limiting enzymes in the mevalonate and lipid biosynthesis pathways led to over 250‐fold higher squalene accumulation than a control strain. However, deletion of POX1 and PXA2 in the tHMG1 overexpressing yeast did not improve squalene accumulation additionally. Fed‐batch fermentation of the tHMG1 and DGA1 co‐overexpressing yeast strain resulted in the production of squalene at a titer of 445.6 mg/L in a nitrogen‐limited minimal medium. This report demonstrates that increasing storage capacity for hydrophobic compounds can enhance squalene production, suggesting that increasing lipid content is an effective strategy to overproduce a hydrophobic molecule in yeast.
Effects of benzoxazine resin on property enhancement of shape memory epoxy: A dual function of benzoxazine resin as a curing agent and a stable network segment

An ability of bisphenol-A/aniline based benzoxazine resin (BA-a) to simultaneously acts as a curing agent and a stable or rigid network segment for shape memory epoxy, i.e. a two component system, is demonstrated. This significantly simplifies a formulation of present shape memory epoxy systems, i.e. a three or four component system. A suitable content of BA-a in the aliphatic epoxy (NGDE)/polybenzoxazine (PBA-a) samples for good shape memory performance is in a range of 30 to 50 mol%. The storage modulus of the obtained NGDE/PBA-a shape memory polymers (SMPs) was increased from 3.57 GPa for 30 mol% BA-a content to 4.50 GPa for 50 mol% BA-a content. Glass transition temperature of the sample was also substantially increased with increasing BA-a fraction, i.e. from 51oC to 140oC. Flexural modulus and strength at room temperature of the samples at 50 mol% BA-a were found to be as high as 3.97 GPa and 132 MPa compared to the maximum values of 2.54 GPa and 100 MPa of SMP based on cyanate ester-epoxy. All samples exhibited a high value of shape fixity close to 100%. A presence of the BA-a in the samples also imparted a greater recovery stress ranging from 0.25 to 1.59 MPa. Consequently, the obtained NGDE/PBA-a copolymers are highly attractive for shape memory materials to be used in a broader range of applications particularly at elevated temperature and a higher recovery stress value.
Replication of Zika Virus in Human Prostate Cells: A Potential Source of Sexually Transmitted Virus

Background While Zika virus (ZIKV) is mainly transmitted by mosquitoes, numerous cases of sexual transmission have been reported during recent outbreaks. Little is known about which host cell types or entry factors aid in mediating this sexual transmission. Methods In this study, we investigated ZIKV cell tropism by infecting 2 types of human prostate cells with 3 contemporary ZIKV isolates from persons infected in the Americas. We used real-time quantitative polymerase chain reaction and immunofluorescence analyses to measure infection and flow cytometry to detect entry factor expression. Results Here we show that ZIKV infects, replicates, and produces infectious virus in prostate stromal mesenchymal stem cells, epithelial cells, and organoids made with a combination of these cells. We also show that prostate cells express several well-characterized flavivirus attachment factors. In contrast, dengue virus does not infect or does not replicate in these prostate cells, although it is known to use similar receptors. Conclusions Our results indicate that ZIKV favors infection of stromal cells more so than epithelial cells in organoids, possibly indicating a preference for stem cells in general. Overall, these results suggest that ZIKV replication occurs in the human prostate and can account for ZIKV secretion in semen, thus leading to sexual transmission.
Electroencephalographic modulations during an open- or closed-eyes motor task

There is fundamental knowledge that during the resting state cerebral activity recorded by electroencephalography (EEG) is strongly modulated by the eyes-closed condition compared to the eyes-open condition, especially in the occipital lobe. However, little research has demonstrated the influence of the eyes-closed condition on the motor cortex, particularly during a self-paced movement. This prompted the question: How does the motor cortex activity change between the eyes-closed and eyes-open conditions? To answer this question, we recorded EEG signals from 15 voluntary healthy subjects who performed a simple motor task (i.e., a voluntary isometric flexion of the right-hand index) under two conditions: eyes-closed and eyes-open. Our results confirmed strong modulation in the mu rhythm (7–13 Hz) with a large event-related desynchronisation. However, no significant differences have been observed in the beta band (15–30 Hz). Furthermore, evidence suggests that the eyes-closed condition influences the behaviour of subjects. This study gives us greater insight into the motor cortex and could also be useful in the brain-computer interface (BCI) domain.
The thermal diffusivity of silicon nitride/silicon carbide nanocomposites using a photothermal deflection technique

Measurements are presented to show the effect of mass fraction on thermal diffusivity of composites fabricated from 200 nm silicon carbide particles dispersed in a matrix of silicon nitride. The mean composite thermal diffusivity is measured over a mass fraction range of 0.05 to 0.30 using a photothermal deflection technique which creates a frequency–dependent thermal penetration depth in the material that can be used to reveal local inhomogeneities of thermal diffusivity. The results show that a maximum thermal diffusivity occurs at a mass fraction of 0.10. This peak value follows extrema in fracture toughness and creep rate at this particle loading that had been observed in prior studies of similarly fabricated nanocomposites. The results are discussed in terms of the competing influences of large thermal diffusivity of silicon carbide relative to silicon nitride, and the role of interfaces as volume fraction is changed due to the high surface–to–volume ratio of the nanosize particles. The measurements are compared with literature values and the trends are explained in terms of the differing particle sizes and binders used in the composites.
Synthesis, Properties and Hydration Characteristics of Novel Nano-Size Mineral Trioxide and Tetracalcium Phosphate for Dental Applications

Nano particles made of pure single phase Mineral trioxide [tricalcium silicate (C3S)] and Tetracalcium phosphate (TTCP) bio ceramics were prepared via solid state reaction at high temperature. Setting times, compressive strength, pH, XRD, FTIR and scanning electron microscopy (SEM) were investigated. Cytotoxicity and antibacterial activity of both C3S and TTCP to human gingival fibroblasts were studied. Both C3S and TTCP compounds undergo hydration reaction when mixed with distilled water. A delayed setting time and very poor mechanical properties for TTCP were detected compared to those of C3S phase. The nano-structure C3S bio ceramic was found to be completely safe to BHK cells compared with TTCP. The prepared C3S and TTCP pastes were applied to the demineralized dentin specimens for seven days. The ultramorphology of dentin revealed that both C3S and TTCP are successful in dentinal tubules occlusion, thus they are beneficial for dental application in the treatment of teeth hypersensitivity.
Static and Dynamic Energy-Absorption Capacity of Graphite-Epoxy Tubular Specimens

This article examines the energy-absorption capacity of 50k and 12k carbon fiber composite tubular specimens crushed axially, in both quasi-static and dynamic fashions. Round and square tubular specimens with - 45° and - 45°/0° fiber orientation schemes were studied. The fundamental issue was to compare the energy-absorption capacity of the lower-cost 50k material with the 12k material, and to examine the influence of specimen geometry, fiber orientation schemes, and dynamic effects on the energyabsorption characteristics. Specimens made from the 50k material absorbed less energy than similar specimens made with the 12k material, and the load ratios were generally higher for the 50k specimens. The square specimens tended to have lower values of specific energy absorption (SEA) than the circular specimens. In addition, the crush modes were somewhat different and the load ratios were generally higher for the square specimens than for the circular specimens. Changing the fiber orientation schemes did not hav.
Effect of minimum quantity lubrication with Al2O3 nanoparticles on surface roughness, tool wear and temperature dissipation in machining Inconel 600 alloy

Eco-friendly machining processes are gaining importance to avoid environmental pollution. Even though cutting fluids have a reasonably low cost, their handling and carrying costs are very high and also, owing to their toxic nature, dumping of used fluids is a big problem because it can be hazardous to workers and also to the environment. To avoid these problems, a minimal-cutting-fluid technique called minimum quantity lubrication (MQL) was used in machining. Owing to the development of nanomaterials by nanotechnology techniques, the effectiveness of the cutting fluids can be increased by dispersing them. In the present work a vegetable-oil-based MQL with different volume fraction of Al2O3 (aluminium oxide) nanoparticles is used as the cutting fluid for machining Inconel 600 alloy. Experimental results for three different conditions – dry, MQL, MQL + Al2O3 nanoparticles – are plotted. It is observed that surface finish and temperature dissipation of the workpiece increase with different volume fractions of Al2O3 nanoparticle addition. It is also possible to observe a decrease in cutting forces and tool wear rate, and a reduction in the negative environmental effects, owing to Al2O3 nanoparticle addition to MQL in machining Inconel 600 alloy.
Neural Correlates of Decision-Making Under Ambiguity and Conflict

HIGHLIGHTS We use a simple gambles design in an fMRI study to compare two conditions: ambiguity and conflict. Participants were more conflict averse than ambiguity averse. Ambiguity aversion did not correlate with conflict aversion. Activation in the medial prefrontal cortex correlated with ambiguity level and ambiguity aversion. Activation in the ventral striatum correlated with conflict level and conflict aversion. Studies of decision making under uncertainty generally focus on imprecise information about outcome probabilities (“ambiguity”). It is not clear, however, whether conflicting information about outcome probabilities affects decision making in the same manner as ambiguity does. Here we combine functional magnetic resonance imaging (fMRI) and a simple gamble design to study this question. In this design the levels of ambiguity and conflict are parametrically varied, and ambiguity and conflict gambles are matched on expected value. Behaviorally, participants avoided conflict more than ambiguity, and attitudes toward ambiguity and conflict did not correlate across participants. Neurally, regional brain activation was differentially modulated by ambiguity level and aversion to ambiguity and by conflict level and aversion to conflict. Activation in the medial prefrontal cortex was correlated with the level of ambiguity and with ambiguity aversion, whereas activation in the ventral striatum was correlated with the level of conflict and with conflict aversion. These novel results indicate that decision makers process imprecise and conflicting information differently, a finding that has important implications for basic and clinical research.
Large‐Size Growth of Ultrathin SnS2 Nanosheets and High Performance for Phototransistors

2D SnS2 nanosheets have been attracting intensive attention as one potential candidate for the modern electronic and/or optoelectronic fields. However, the controllable large‐size growth of ultrathin SnS2 nanosheets still remains a great challenge and the photodetectors based on SnS2 nanosheets suffer from low responsivity, thus hindering their further applications so far. Herein, an improved chemical vapor deposition route is provided to synthesize large‐size SnS2 nanosheets, the side length of which can surpass 150 μm. Then, ultrathin SnS2 nanosheet‐based phototransistors are fabricated, which achieve high photoresponsivities up to 261 A W−1 (with a fast rising time of 20 ms and a falling time of 16 ms) in air and 722 A W−1 in vacuum, respectively. Furthermore, the effects of back‐gate voltage and air adsorbates on the optoelectronic properties of the SnS2 nanosheet have been systematically investigated. In addition, a high‐performance flexible photodetector based on SnS2 nanosheet is also fabricated with a high responsivity of 34.6 A W−1.
Analysis of Escherichia coli Mutants with a Linear Respiratory Chain

The respiratory chain of E. coli is branched to allow the cells' flexibility to deal with changing environmental conditions. It consists of the NADH:ubiquinone oxidoreductases NADH dehydrogenase I and II, as well as of three terminal oxidases. They differ with respect to energetic efficiency (proton translocation) and their affinity to the different quinone/quinol species and oxygen. In order to analyze the advantages of the branched electron transport chain over a linear one and to assess how usage of the different terminal oxidases determines growth behavior at varying oxygen concentrations, a set of isogenic mutant strains was created, which lack NADH dehydrogenase I as well as two of the terminal oxidases, resulting in strains with a linear respiratory chain. These strains were analyzed in glucose-limited chemostat experiments with defined oxygen supply, adjusting aerobic, anaerobic and different microaerobic conditions. In contrast to the wild-type strain MG1655, the mutant strains produced acetate even under aerobic conditions. Strain TBE032, lacking NADH dehydrogenase I and expressing cytochrome bd-II as sole terminal oxidase, showed the highest acetate formation rate under aerobic conditions. This supports the idea that cytochrome bd-II terminal oxidase is not able to catalyze the efficient oxidation of the quinol pool at higher oxygen conditions, but is functioning mainly under limiting oxygen conditions. Phosphorylation of ArcA, the regulator of the two-component system ArcBA, besides Fnr the main transcription factor for the response towards different oxygen concentrations, was studied. Its phosphorylation pattern was changed in the mutant strains. Dephosphorylation and therefore inactivation of ArcA started at lower aerobiosis levels than in the wild-type strain. Notably, not only the micro- and aerobic metabolism was affected by the mutations, but also the anaerobic metabolism, where the respiratory chain should not be important.
Neuronal Circuit Policies

We propose an effective way to create interpretable control agents, by re-purposing the function of a biological neural circuit model, to govern simulated and real world reinforcement learning (RL) test-beds. We model the tap-withdrawal (TW) neural circuit of the nematode, C. elegans, a circuit responsible for the worm's reflexive response to external mechanical touch stimulations, and learn its synaptic and neuronal parameters as a policy for controlling basic RL tasks. We also autonomously park a real rover robot on a pre-defined trajectory, by deploying such neuronal circuit policies learned in a simulated environment. For reconfiguration of the purpose of the TW neural circuit, we adopt a search-based RL algorithm. We show that our neuronal policies perform as good as deep neural network policies with the advantage of realizing interpretable dynamics at the cell level.
CONTINUUM THERMODYNAMIC AND VARIATIONAL MODELING AND SIMULATION OF DUCTILE FAILURE AT LARGE DEFORMATION WITH APPLICATION TO ENGINEERING STRUCTURES

Summary The purpose of this work is the extension of local Gurson-base d ductile damage and failure modeling in engineering materi als and structures to account for the non-local nature of void coale scence. In particular, the extension pursued here is based o n the introduction of an non-local effective damage parameter analogous to that f of Needleman and Tvergaard which is modeled thermodynamicall y as a scalar-valued continuum microstructural field or gener alized phase field via a recent thermodynamic approach. In th e simplest case, the resulting field relation for is formally analogous to the inhomogeneous temperature equ ation. As such, analogous to temperature, represents an additional continuum degree-of-freedom her e. And in the complete model, damage and deformation are coupled. Further, the field relation for contains a characteristic length determining the effectiv e dimension of the process zone for void coelescence.
Wirkungsweisen nanoskaliger Böhmite in einem Polymer und seinem Kohlenstofffaserverbund unter Druckbelastung

Increasing ecological awareness as well as quality and safety demands, which are present, for instance, in the aerospace and automotive sectors, lead to the need to use more sophisticated and more effective materials. For that purpose, laminates of carbon fiber reinforced plastic (CFRP), which are manufactured by injection technology, are reinforced with boehmite particles. This doping strengthens the laminates, whose original properties are weaker than prepregs. Besides the shear strength, compression strength and the damage tolerance, the mode of action of the nanoparticles in resin and in CFRP is also analyzed. It thereby reveals that the hydroxyl groups and even more a taurine modification of the boehmites’ surface alter the elementary polymer morphology. Consequently a new flow and reaction comportment, lower glass transition temperatures and shrinkage, as well as a changed mechanical behavior occur. Due to a structural upgrading of the matrix (higher shear stiffness, reduced residual stress), a better fiber-matrix adhesion, and differing crack paths, the boehmite nanoparticles move the degradation barrier of the material to higher loadings, thus resulting in considerably upgraded new CFRP.
Sheep can be used as animal model of regional myocardial remodeling and controllable work

Background Pacing the right heart has been shown to induce reversible conduction delay and subsequent asymmetric remodeling of the left ventricle (LV) in dogs and pigs. Both species have disadvantages in animal experiments. Therefore the aim of this study was to develop a more feasible and easy-to-use animal model in sheep. Methods Dual-chamber (DDD) pacemakers with epicardial leads on the right atrium and right ventricular free wall were implanted in 13 sheep. All animals underwent 8 weeks of chronic rapid pacing at 180 bpm. Reported observations were made at 110 bpm. Results DDD pacing acutely induced a left bundle branch block (LBBB) — like pattern with almost doubling in QRS width and the appearance of a septal flash, indicating mechanical dyssynchrony. Atrial pacing (AAI) resulted in normal ventricular conduction and function. During 8 weeks of rapid DDD pacing, animals developed LV remodeling (confirmed with histology) with septal wall thinning (−30%, p < 0.05), lateral wall thickening (+22%, p < 0.05), LV volume increase (+32%, p < 0.05), decrease of LV ejection fraction (−31%, p < 0.05), and functional mitral regurgitation. After 8 weeks, segmental pressure-strain-loops, representing regional myocardial work, were recorded. Switching from AAI to DDD pacing decreased immediately work in the septum and increased it in the lateral wall (−69 and +41%, respectively, p < 0.05). Global LV stroke work and dP/dtmax decreased (−27% and −25%, respectively, p < 0.05). Conclusions This study presents the development a new sheep model with an asymmetrically remodeled LV. Simple pacemaker programing allows direct modulation of regional myocardial function and work. This animal model provides a new and valuable alternative for canine or porcine models and has the potential to become instrumental for investigating regional function and loading conditions on regional LV remodeling.