Miracle-dz/UniFAR-FTUs huggingface dataset:
Simulating Bird Strike on Aircraft Composite Wing Leading Edge.

In this master thesis project the possibility to model the response of a wing when subjected to bird strike using finite elements is analyzed. Since this transient event lasts only a few milliseconds the used solution method is explicit time integration. The wing is manufactured using carbon fiber laminate. Carbon fiber laminates have orthotropic material properties with different stiffness in different directions. Accordingly, there are damagemechanisms not considered when using metal that have to be modeled when using composites. One of these damage mechanisms is delamination which occurs when cured layers inside a component become separated. To simulate this phenomenon, multiple layers of shell elements with contact in between are used as a representation of the interface where a component is likely to delaminate.By comparing experimental and simulated results the model of delamination is verified and the influence of different parameters on the results is investigated. Furthermore, studies show that modeling delamination layers in each possible layer of a composite stack is not optimal due to the fact that the global stiffness of the laminate is decreased as more layers are modeled. However, multiple layers are needed in order to mitigate the spreading of delamination and obtain realistic delaminated zones.As the laminates are comprised of carbon fiber and epoxy sheets it is of importance to include damage mechanisms inside each individual sheet. Accordingly, a composite material model built into the software is used which considers tensile and compressive stress in fiber and epoxy. The strength limits are then set according to experimental test data.The bird is modeled using a mesh free technique called Smooth Particle Hydrodynamics using a material model with properties similar to a fluid. The internal pressure of the bird model is linked to the change in volume with an Equation of State. By examining the bird models behavior compared to experimental results it is determined to have a realistic impact on structures.A model of the leading edge is then subjected to bird strike according to European standards. The wing skin is penetrated indicating that reinforcements might be needed in order to protect valuable components inside the wing structure such as the fuel tank. However, the results are not completely accurate due to the fact that there is little experimental dataavailable regarding soft body penetration of composite laminates. As a consequence, the simulation cannot be confirmed against real experimental results and further investigations are required in order to have confidence in modeling such events. Furthermore, the delamination due to the bird strike essentially spreads across the whole model. Since only one layer of delamination is included the spread is most likely overestimated.
Time-Variable Refraction of the Internal Tide at the Hawaiian Ridge

AbstractThe interaction of the dominant semidiurnal M2 internal tide with the large-scale subtidal flow is examined in an ocean model by propagating the tide through an ensemble of background fields in a domain centered on the Hawaiian Ridge. The background fields are taken from the Simple Ocean Data Assimilation (SODA) ocean analysis, at 2-month intervals from 1992 through 2001. Tides are computed with the Primitive Equation Z-coordinate Harmonic Analysis of Tides (PEZ-HAT) model by 14-day integrations using SODA initial conditions and M2 tidal forcing. Variability of the tide is found to occur primarily as the result of propagation through the nonstationary background fields, rather than via generation site variability. Generation of incoherent tidal variability is mapped and shown to occur mostly in association with waves generated at French Frigate Shoals scattering near the Musicians Seamounts to the north of the ridge. The phase-coherent internal tide loses energy at a domain-average rate of 2 mW m−.
Structure optimisation to improve the delivery efficiency and cell selectivity of a tumour-targeting cell-penetrating peptide

Abstract Cell-penetrating peptide (CPP) is used for the delivery of biomacromolecules across the cell membrane and is limited in cancer therapy due to the lack of cell selectivity. Epidermal growth factor receptor (EGFR) has been widely used in clinical targeted therapy for tumours. Here, we reported a novel tumour targeting cell-penetrating peptide (TCPP), EHB (ELBD-C6H) with 20-fold and 3000-fold greater transmembrane ability and tumour cell selectivity than our previously reported S3-HBD and classic CPP TAT, respectively. In this new TCPP, a specific alpha helix structure was inserted into a repeated amino acid (AA) sequence formed by tandem multiple selected key AA residues of vaccinia growth factor (VGF), and this sequence was then fused to a tailored heparin binding domain sequence (C6H) derived from heparin-binding epidermal growth factor-like growth factor to intensify its targeting delivery ability. EHB could carry anticancer proteins such as MAP30 (Momordica Antiviral Protein 30 kDa) into EGFR-overexpressing cancer cell and inhibit cell growth, but it had a greatly reduced interaction with normal cells. These results indicated that EHB, as a novel efficient TCPP for the selective delivery of drug molecules into cancer cells, would help to improve the efficacy and safety of anti-tumour drugs.
Regulation of CD4 Receptor and HIV-1 Entry by MicroRNAs-221 and -222 during Differentiation of THP-1 Cells

Human immunodeficiency virus type-1 (HIV-1) infection of monocyte/macrophages is modulated by the levels of entry receptors cluster of differentiation 4 (CD4) and C-C chemokine receptor type 5 (CCR5), as well as by host antiviral restriction factors, which mediate several post-entry blocks. We recently identified two microRNAs, miR-221 and miR-222, which limit HIV-1 entry during infection of monocyte-derived macrophages (MDMs) by down-regulating CD4 expression. Interestingly, CD4 is also down-regulated during the differentiation of monocytes into macrophages. In this study, we compared microRNA expression profiles in primary monocytes and macrophages by RNAseq and found that miR-221/miR-222 are enhanced in macrophages. We took advantage of the monocytic THP-1 cell line that, once differentiated, is poorly susceptible to HIV-1. Accordingly, we found that CD4 levels are very low in THP-1 differentiated cells and that this down-regulation of the virus receptor is the result of miR-221/miR-222 up-regulation during differentiation. We thus established a THP-1 cell line stably expressing a modified CD4 (THP-1-CD4R) that is not modulated by miR-221/miR-222. We show that in contrast to parental THP-1, this line is productively infected by HIV-1 following differentiation, sustaining efficient HIV-1 CD4-dependent replication and spread. This new THP-1-CD4R cell line represents a useful tool for the study of HIV-1-macrophage interactions particularly in contexts where spreading of viral infection is necessary.
Silencing Retinoid X Receptor Alpha Expression Enhances Early-Stage Hepatitis B Virus Infection In Cell Cultures

ABSTRACT Multiple steps of the life cycle of hepatitis B virus (HBV) are known to be coupled to hepatic metabolism. However, the details of involvement of the hepatic metabolic milieu in HBV infection remain incompletely understood. Hepatic lipid metabolism is controlled by a complicated transcription factor network centered on retinoid X receptor alpha (RXRα). Here, we report that RXRα negatively regulates HBV infection at an early stage in cell cultures. The RXR-specific agonist bexarotene inhibits HBV in HepG2 cells expressing the sodium taurocholate cotransporting polypeptide (NTCP) (HepG2-NTCP), HepaRG cells, and primary Tupaia hepatocytes (PTHs); reducing RXRα expression significantly enhanced HBV infection in the cells. Transcriptome sequencing (RNA-seq) analysis of HepG2-NTCP cells with a disrupted RXRα gene revealed that reduced gene expression in arachidonic acid (AA)/eicosanoid biosynthesis pathways, including the AA synthases phospholipase A2 group IIA (PLA2G2A), is associated with increased HBV infection. Moreover, exogenous treatment of AA inhibits HBV infection in HepG2-NTCP cells. These data demonstrate that RXRα is an important cellular factor in modulating HBV infection and implicate the participation of AA/eicosanoid biosynthesis pathways in the regulation of HBV infection. IMPORTANCE Understanding how HBV infection is connected with hepatic lipid metabolism may provide new insights into virus infection and its pathogenesis. By a series of genetic studies in combination with transcriptome analysis and pharmacological assays, we here investigated the role of cellular retinoid X receptor alpha (RXRα), a crucial transcription factor for controlling hepatic lipid metabolism, in de novo HBV infection in cell cultures. We found that silencing of RXRα resulted in elevated HBV covalently closed circular DNA (cccDNA) formation and viral antigen production, while activation of RXRα reduced HBV infection efficiency. Our results also showed that silencing phospholipase A2 group IIA (PLA2G2A), a key enzyme of arachidonic acid (AA) synthases, enhanced HBV infection efficiency in HepG2-NTCP cells and that exogenous AA treatment reduced de novo HBV infection in the cells. These findings unveil RXRα as an important cellular factor in modulating HBV infection and may point to a new strategy for host-targeted therapies against HBV.
Warm compaction of metallic powders

Abstract: Warm compaction is a cost saving and effective method for obtaining high performance powder metallurgy (PM) parts. This chapter presents the principles of warm compaction and technical aspects of the process. The green and sintered properties of warm compacted parts are discussed and compared with conventionally (cold) produced compacts. The applications of the process for ferrous and non-ferrous PM parts are presented and future trends are outlined.
Cigarette Smoking and Adipose Tissue: The Emerging Role in Progression of Atherosclerosis

Smoking is an established risk factor for atherosclerosis through several underlying pathways. Moreover, in the development of atherosclerotic plaque formation, obesity, defined as excess fat mass accumulation, also plays a vital role in dyslipidemia and insulin resistance. Substantial evidence shows that cigarette smoking induces multiple pathological effects in adipose tissue, such as differentiation of adipocytes, lipolysis, and secretion properties in adipose tissue. Therefore, there is an emerging speculation in which adipose tissue abnormality induced by smoking or nicotine is likely to accelerate the progression of atherosclerosis. Herein, this review aims to investigate the possible interplay between smoking and adipose tissue dysfunction in the development of atherosclerosis.
Humans quickly learn to blink strategically in response to environmental task demands

Significance Eye blinks serve the purpose of maintaining healthy vision but during a blink visual information processing is interrupted. While a multitude of medical, cognitive, and psychological factors have been shown to influence blinking, the present study establishes quantitatively how human blinking behavior is dynamically adapted to environmental task demands. In our experiment participants quickly learned to blink strategically. A minimal computational model captures the observed behavior as a trade-off between internal, physiological benefits and external, task-related costs given perceptual uncertainties. Crucially, the model allows predicting an individual subject’s temporal dynamics of blinking and provides an explanation of the long-known distribution of interblink intervals. Taken together, this provides a basis for future research using blinking as a behavioral marker. Eye blinking is one of the most frequent human actions. The control of blinking is thought to reflect complex interactions between maintaining clear and healthy vision and influences tied to central dopaminergic functions including cognitive states, psychological factors, and medical conditions. The most imminent consequence of blinking is a temporary loss of vision. Minimizing this loss of information is a prominent explanation for changes in blink rates and temporarily suppressed blinks, but quantifying this loss is difficult, as environmental regularities are usually complex and unknown. Here we used a controlled detection experiment with parametrically generated event statistics to investigate human blinking control. Subjects were able to learn environmental regularities and adapted their blinking behavior strategically to better detect future events. Crucially, our design enabled us to develop a computational model that allows quantifying the consequence of blinking in terms of task performance. The model formalizes ideas from active perception by describing blinking in terms of optimal control in trading off intrinsic costs for blink suppression with task-related costs for missing an event under perceptual uncertainty. Remarkably, this model not only is sufficient to reproduce key characteristics of the observed blinking behavior such as blink suppression and blink compensation but also predicts without further assumptions the well-known and diverse distributions of time intervals between blinks, for which an explanation has long been elusive.
Effect of thermal shock on interlaminar strength of thermally aged glass fiber-reinforced epoxy composites

Glass fiber/epoxy composites were thermally conditioned at 50, 100, 150, 200, and 250°C for different periods of time and then immediately quenched directly in ice-cold water from each stage of conditioning temperature. The polymerization or depolymerization by thermal conditioning and the debonding effect by concurrently following thermal shock in polymer composites are assessed in the present study. The short-beam shear tests were performed at room temperature on the quenched samples to evaluate the value of interlaminar shear strength of the composites. The short conditioning time followed by thermal shock resulted in reduction of shear strength of the composites. The strength started regaining its original value with longer conditioning time. Conditioning at 250°C and thereafter quenching yielded a sharp and continuous fall in the shear strength. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2062–2066, 2006
Analysis of radiation effects in two irradiated tumor spheroid models

Multicellular spheroids have proven suitable as three-dimensional in vivo-like models of non-vascularized micrometastases. Unlike monolayer-based models, spheroids mirror the cellular milieu and the pathophysiological gradients inside tumor nodules. However, there is limited knowledge of the radiation effects at the molecular level in spheroids of human origin. The present study is a presentation of selected cell biological processes that may easily be analyzed with methods available at routine pathology laboratories. Using gamma irradiated pancreatic neuroendocrine BON1 and colonic adenocarcinoma HCT116 spheroids as model systems, the present study assessed the radiobiological response in these models. Spheroid growth after irradiation was followed over time and molecular responses were subsequently assessed with immunohistochemistry (IHC) staining for descriptive analyses and semi-automatic grading of apoptosis, G2-phase and senescence in thin sections of the spheroids. Growth studies demonstrated the BON1 spheroids were slower growing and less sensitive to radiation compared with the HCT116 spheroids. IHC staining for G2-phase was primarily observed in the outer viable P-cell layers of the spheroids, with the 6 Gy irradiated HCT116 spheroids demonstrating a very clear increase in staining intensity compared with unirradiated spheroids. Apoptosis staining results indicated increased apoptosis with increasing radiation doses. No clear association between senescence and radiation exposure in the spheroids were observed. The present results demonstrate the feasibility of the use of multicellular spheroids of human origin in combination with IHC analyses to unravel radiobiological responses at a molecular level. The present findings inspire further investigations, including other relevant IHC-detectable molecular processes in time- and radiation dose-dependent settings.
Using a network organisational architecture to support the development of Learning Healthcare Systems

The US National Academy of Sciences has called for the development of a Learning Healthcare System in which patients and clinicians work together to choose care, based on best evidence, and to drive discovery as a natural outgrowth of every clinical encounter to ensure innovation, quality and value at the point of care. However, the vision of a Learning Healthcare System has remained largely aspirational. Over the last 13 years, researchers, clinicians and families, with support from our paediatric medical centre, have designed, developed and implemented a network organisational model to achieve the Learning Healthcare System vision. The network framework aligns participants around a common goal of improving health outcomes, transparency of outcome measures and a flexible and adaptive collaborative learning system. Team collaboration is promoted by using standardised processes, protocols and policies, including communication policies, data sharing, privacy protection and regulatory compliance. Learning methods include collaborative quality improvement using a modified Breakthrough Series approach and statistical process control methods. Participants observe their own results and learn from the experience of others. A common repository (a ‘commons’) is used to share resources that are created by participants. Standardised technology approaches reduce the burden of data entry, facilitate care and result in data useful for research and learning. We describe how this organisational framework has been replicated in four conditions, resulting in substantial improvements in outcomes, at scale across a variety of conditions.
Annals of the New York Academy of Sciences the Insula: a Critical Neural Substrate for Craving and Drug Seeking under Conflict and Risk

Drug addiction is characterized by the inability to control drug use when it results in negative consequences or conflicts with more adaptive goals. Our previous work showed that damage to the insula disrupted addiction to cigarette smoking—the first time that the insula was shown to be a critical neural substrate for addiction. Here, we review those findings, as well as more recent studies that corroborate and extend them, demonstrating the role of the insula in (1) incentive motivational processes that drive addictive behavior, (2) control processes that moderate or inhibit addictive behavior, and (3) interoceptive processes that represent bodily states associated with drug use. We then describe a theoretical framework that attempts to integrate these seemingly disparate findings. In this framework, the insula functions in the recall of interoceptive drug effects during craving and drug seeking under specific conditions where drug taking is perceived as risky and/or where there is conflict between drug taking and more adaptive goals. We describe this framework in an evolutionary context and discuss its implications for understanding the mechanisms of behavior change in addiction treatments.
Preparation and Evaluation of Adsorbents from Coal and Irvingia gabonensis Seed Shell for the Removal of Cd(II) and Pb(II) Ions from Aqueous Solutions

Cd(II) and Pb(II) ions removal using adsorbents prepared from sub-bituminous coal, lignite, and a blend of coal and Irvingia gabonensis seed shells was investigated. Fourier transform infrared, scanning electron microscope and X-ray fluorescence analyses implicated hydroxyl, carbonyl, Al2O3, and SiO2 as being responsible for attaching the metal ions on the porous adsorbents. The optimum adsorption of carbonized lignite for the uptake of Cd(II) and Pb(II) ions from aqueous media were 80.93 and 87.85%, respectively. Batch adsorption was done by effect of adsorbent dosage, pH, contact time, temperature, particle size, and initial concentration. Equilibrium for the removal of Pb(II) and Cd(II) was established within 100 and 120 min respectively. Blending the lignite-derived adsorbent with I. gabonensis seed shell improved the performance significantly. More improvement was observed on modification of the blend using NaOH and H3PO4. Pb(II) was preferentially adsorbed than Cd(II) in all cases. Adsorption of Cd(II) and Pb(II) ions followed Langmuir isotherm. The adsorption kinetics was best described by pseudo-second order model. The potential for using a blend of coal and agricultural byproduct (I. gabonensis seed shell) was found a viable alternative for removal of toxic heavy metals from aqueous solutions.
Diagnostic value of glutamate with 2-hydroxyglutarate in magnetic resonance spectroscopy for IDH1 mutant glioma.

BACKGROUND Mutations in the isocitrate dehydrogenase 1 (IDH1) gene that are frequently observed in low-grade glioma are strongly associated with the accumulation of 2-hydroxyglutarate (2HG), which is a valuable diagnostic and prognostic biomarker of IDH1 mutant glioma. However, conventional MR spectroscopy (MRS)-based noninvasive detection of 2HG is challenging. In this study, we aimed to determine the additional value of other metabolites in predicting IDH1 mutations with conventional MRS. METHODS Forty-seven patients with glioma underwent conventional single voxel short echo time MRS prior to surgery. A stereotactic navigation-guided operation was performed to resect tumor tissues in the center of the MRS voxel. MRS-based measurements of metabolites were validated with gas chromatography-mass spectrometry. We also conducted integrated analyses of glioma cell lines and clinical samples to examine the other metabolite levels and molecular findings in IDH1 mutant gliomas. RESULTS A metabolomic analysis demonstrated higher levels of 2HG in IDH1 mutant glioma cells and surgical tissues. Interestingly, glutamate levels were significantly decreased in IDH1 mutant gliomas. Through an analysis of metabolic enzyme genes in glutamine pathways, it was shown that the expressions of branched-chain amino acid transaminase 1 were reduced and glutamate dehydrogenase levels were elevated in IDH1 mutant gliomas. Conventional MRS detection of glutamate and 2HG resulted in a high diagnostic accuracy (sensitivity 72%, specificity 96%) for IDH1 mutant glioma. CONCLUSIONS IDH1 mutations alter glutamate metabolism. Combining glutamate levels optimizes the 2HG-based monitoring of IDH1 mutations via MRS and represents a reliable clinical application for diagnosing IDH1 mutant gliomas.