Miracle-dz/UniFAR-FTUs huggingface dataset:
Generation of Persister Cells of Pseudomonas aeruginosa and Staphylococcus aureus by Chemical Treatment and Evaluation of Their Susceptibility to Membrane-Targeting Agents

Persister cells (PCs) are a subset of dormant, phenotypic variants of regular bacteria, highly tolerant to antibiotics. Generation of PCs in vivo may account for the recalcitrance of most chronic infections to antimicrobial treatment and demands for the identification of new antimicrobial agents able to target such cells. The present study explored the possibility to obtain in vitro PCs of Pseudomonas aeruginosa and Staphylococcus aureus at high efficiency through chemical treatment, and to test their susceptibility to structurally different antimicrobial peptides (AMPs) and two clinically used peptide-based antibiotics, colistin and daptomycin. The main mechanism of action of these molecules (i.e., membrane-perturbing activity) renders them potential candidates to act against dormant cells. Exposure of stationary-phase cultures to optimized concentrations of the uncoupling agent cyanide m-chlorophenylhydrazone (CCCP) was able to generate at high efficiency PCs exhibiting an antibiotic-tolerant phenotype toward different classes of antibiotics. The metabolic profile of CCCP-treated bacteria was investigated by monitoring bacterial heat production through isothermal microcalorimetry and by evaluating oxidoreductase activity by flow cytometry. CCCP-pretreated bacteria of both bacterial species underwent a substantial decrease in heat production and oxidoreductase activity, as compared to the untreated controls. After CCCP removal, induced persisters showed a delay in heat production that correlated with a lag phase before resumption of normal growth. The metabolic reactivation of bacteria coincided with their reversion to an antibiotic-sensitive phenotype. Interestingly, PCs generated by CCCP treatment resulted highly sensitive to three different membrane-targeting AMPs at levels comparable to those of CCCP-untreated bacteria. Colistin was also highly active against PCs of P. aeruginosa, while daptomycin killed PCs of S. aureus only at concentrations 32 to 64-fold higher than those of the tested AMPs. In conclusion, CCCP treatment was demonstrated to be a suitable method to generate in vitro PCs of medically important bacterial species at high efficiency. Importantly, unlike conventional antibiotics, structurally different AMPs were able to eradicate PCs suggesting that such molecules might represent valid templates for the development of new antimicrobials active against persisters.
High maneuverability guidewire with functionally graded properties using new superelastic alloys

Nitinol shape memory alloys (SMAs) are attracting considerable attention as core materials for medical guidewires because of their excellent flexibility and shape retention. However, since Nitinol guidewires possess low rigidity, the pushability and torquability of the guidewires are insufficient. On the other hand, although guidewires made of stainless steel have high pushability, plastic deformation occurs easily. We have developed a new class of superelastic guidewires with functionally graded properties from the tip to the end by using new SMA core materials such as Cu‐Al‐Mn‐based or Ni‐free Ti‐Mo‐Sn SMAs. The tip portion of the guidewire shows excellent superelasticity (SE), while the body portion possesses high rigidity. These functionally graded characteristics can be realized by microstructural control. These guidewires with functionally graded properties show excellent pushability and torquability and are considerably easier to handle than conventional guidewires with Nitinol or stainless steel cores. Moreover, a metallic catheter using a Ni‐free Ti‐based SMA with high biocompatibility is introduced.
Tensile properties of low density polypropylene (LDPE)/palm kernel shell (PKS) biocomposites: The effect of acrylic acid (AA)

The surface of palm kernel was modified by acrylic acid (AA). Low density polyethylene (LDPE) was filled by palm kernel shell at various 0, 10, 20, 30 and 40 php. The effect of AA as a coupling agent on LDPE/PKS biocomposites on tensile properties and morphology was investigated. The results show that the increasing of filler content decreased the tensile strength and break elongation but increased the Young's modulus. The presence of AA indicates higher tensile strength and Young's modulus but lower elongation at break compared to untreated LDPE/PKS biocomposites. The scanning electron microscope study show that the better interfacial interaction between palm kernel shell and low density polyethylene with addition of AA.
Large-scale cooperative co-evolution with bi-objective selection based imbalanced multi-modal optimization

Cooperative co-evolutionary algorithm (CC) which runs in a divide-and-conquer manner is effective to solve large-scale global optimization (LSGO) problems. Multi-modal optimization (MMO) intends to locate multiple optimal solutions. Using MMO methods in CC algorithm would be beneficial, because MMO optimizer can provide more information about the landscapes. In this paper, a bi-objective selection is proposed to introduce imbalance among the subpopulations of a MMO optimizer. Only the highly representative subpopulations will be active and evolved in the MMO procedure. With this imbalanced MMO technique, the CC's subcomponents could obtain sufficient coevolutionary information (multiple optima) from each other. In addition, more computational resources could be saved and used in CC procedure. Experiments and statistical comparisons are conducted on LSGO benchmark functions to verify the effectiveness of the proposed method. The results indicate that the proposed algorithm significantly outperforms seven state-of-the-art large-scale CC algorithms.
Divergent selection and heterogeneous genomic divergence

Levels of genetic differentiation between populations can be highly variable across the genome, with divergent selection contributing to such heterogeneous genomic divergence. For example, loci under divergent selection and those tightly physically linked to them may exhibit stronger differentiation than neutral regions with weak or no linkage to such loci. Divergent selection can also increase genome‐wide neutral differentiation by reducing gene flow (e.g. by causing ecological speciation), thus promoting divergence via the stochastic effects of genetic drift. These consequences of divergent selection are being reported in recently accumulating studies that identify: (i) ‘outlier loci’ with higher levels of divergence than expected under neutrality, and (ii) a positive association between the degree of adaptive phenotypic divergence and levels of molecular genetic differentiation across population pairs [‘isolation by adaptation’ (IBA)]. The latter pattern arises because as adaptive divergence increases, gene flow is reduced (thereby promoting drift) and genetic hitchhiking increased. Here, we review and integrate these previously disconnected concepts and literatures. We find that studies generally report 5–10% of loci to be outliers. These selected regions were often dispersed across the genome, commonly exhibited replicated divergence across different population pairs, and could sometimes be associated with specific ecological variables. IBA was not infrequently observed, even at neutral loci putatively unlinked to those under divergent selection. Overall, we conclude that divergent selection makes diverse contributions to heterogeneous genomic divergence. Nonetheless, the number, size, and distribution of genomic regions affected by selection varied substantially among studies, leading us to discuss the potential role of divergent selection in the growth of regions of differentiation (i.e. genomic islands of divergence), a topic in need of future investigation.
Association of Low Luminance Questionnaire With Objective Functional Measures in Early and Intermediate Age-Related Macular Degeneration

Purpose To determine whether Low Luminance Questionnaire (LLQ) scores are associated with objective measures of visual function in early and intermediate age-related macular degeneration (AMD). Methods Cross-sectional study of subjects with early AMD Age-Related Eye Disease Study (AREDS) stage 2, N = 33), intermediate AMD (AREDS stage 3, N = 47), and age-matched healthy controls (N = 21). Subjects were interviewed with the LLQ. Psychophysical tests performed included best-corrected visual acuity (BCVA), mesopic microperimetry, dark adaptometry (DA), low luminance visual acuity (LLVA), and cone contrast test (CCT). Low luminance deficit (LLD) was the difference in the number of letters read under photopic versus low luminance settings. The relationship between LLQ and visual function test scores was assessed with linear regression. Results Subjects with intermediate AMD had significantly lower LLQ composite scores (mean = 75.8 ± 16.7; median = 76, range [29, 97]) compared with early AMD (mean = 85.3 ± 13.3; median = 88, range [50, 100], P = 0.007) or controls (mean = 91.4 ± 6.5; median = 94, range [79, 99], P < 0.001) in the overall cohort. LLQ composite scores were associated with computerized BCVA (β = 0.516), computerized LLVA at two background luminance (1.3 cd/m2, β = 0.660; 0.5 cd/m2, β = 0.489) along with their respective computerized LLDs (β = −0.531 and −0.467), rod intercept (β = −0.312), and CCT green (β = 0.183) (all P < 0.05). Only the computerized LLVAs and computerized LLDs remained statistically significant after adjusting for AMD versus control status (P < 0.05). Among AMD subjects, LLQ composite scores were significantly associated with the computerized LLVAs (β = 0.622 and 0.441) and LLDs (β = −0.795 and −0.477) at both the 1.3 and 0.5 cd/m2 luminance levels, respectively, and these associations remained significant after adjusting for AMD severity (P < 0.05). Conclusions Among subjects with early and intermediate AMD, LLQ scores were significantly associated with computerized LLVA and LLD. LLQ is a useful patient-centered functional measure of visual impairment in early and intermediate AMD.
Nanometer-scale technology and near-field characterization of InP-based planar photonic-crystal devices

Photonic crystals consist of an ensemble of periodic optical scatterers which, through their coherent interaction, induce a photonic band structure and eventually a band gap for certain optical frequencies. Photonic crystals promise to greatly enhance the control over the flow of light and, consequently, to initiate important technological developments in the fields of semiconductor lasers, LED-based lighting or highly integrated all-optical signal processing. The fabrication of photonic crystals at telecommunications (1.3-1.55μm) or visible wavelengths requires fabrication methods (patterning and pattern transfer) with nanometer-scale accuracy. In view of optoelectronic applications, the first part of this dissertation describes technology developments to fabricate planar photonic crystal structures in the InP material system. In the second part, transmission and near-field optical measurements are described to characterize the fabricated devices. As the first step in fabrication, the lithography determines to a large extent the accuracy with which nano-structures can be fabricated. Using electron-beam lithography, special emphasis has to be put on correcting proximity effects which are particularly sever due to the combination of the high electron backscatter efficiency of InP and the high density of objects in a photonic crystal design. In the course of this work, a proximityeffect correction software was developed which is tailored to the needs of photonic-crystal fabrication. In collaboration with Raith GmbH the software was extended to fulfill the requirements of general nano-patterning and was commercialized under the brand name “NanoPECS”. As a step further, a newly developed simulation method based on the energy deposition in the resist, was used to assess the accuracy limits of different proximity-effect correction methods and to investigate the effect of proximity and geometrical parameters on the lithography result. It was found
Rifaximin Plus Levofloxacin-Based Rescue Regimen for the Eradication of Helicobacter pylori

Background/Aims This study assessed the efficacy of a rifaximin plus levofloxacin-based rescue regimen in patients that had failed both triple and quadruple standard regimens for the eradication of Helicobacter pylori. Methods We treated patients for H. pylori between August 2009 and April 2011. The triple regimen consisted of combined treatment with amoxicillin, clarithromycin, and pantoprazole for 1 week. For failed cases, a quadruple regimen of tetracycline, metronidazole, bismuth dicitrate, and lansoprazole for 1 week was administered. The rescue regimen for persistently refractory cases was rifaximin 200 mg t.i. d. , levofloxacin 500 mg q.d. , and lansoprazole 15 mg b.i. d. for 1 week. Results In total, 482 patients were enrolled in this study. The eradication rates associated with the first and second regimens were 58% and 60%, respectively. Forty-seven out of 58 patients who failed with the second-line regimen received rifaximin plus levofloxacin-based third-line therapy. The eradication rate for the third regimen was 65%. The cumulative eradication rates were 58%, 85%, and 96% for each regimen, respectively. Conclusions A rifaximin plus levofloxacin-based regimen could be an alternative rescue therapy in patients with resistance to both triple and quadruple regimens for the eradication of H. pylori.
Metastasis: a review of recent advances.

Recent developments in research on metastasis have been reviewed. The process of metastasis begins when cells of the primary cancer invade surrounding tissues. At least one major factor responsible for this invasion is decreased adhesiveness of cancer cells, a property associated with deficient calcium and macromolecular abnormalities on the cell surface. Because of decreased adhesiveness cancer cells can separate from each other, move into surrounding tissues, and penetrate vessels. Following vascular invasion, tumor cell emboli are discharged into the blood stream. Most of these emboli are arrested by the first capillary or arteriolar bed, but some emboli may immediately pass through the capillaries and be carried to other regions. The pattern of distribution of metastases depends in part on mechanical factors and, in part, on recently recognized effects of hormones, notably of the adrenal. These hormones act on the tumor embolus or on the tissue where it has lodged. Studies on the lymphatic spread of cancer reveal that tumor cell emboli of carcinomas are arrested in the subcapsular sinus of one or more lobules of the lymph node, and it is here that early growth occurs. The cancer is contained by the node for some time before spread to the next node occurs. While growing in a node, the cancer has no supply of lymphatic vessels. When tumor emboli reach the thoracic duct, some of them may go directly to nearby lymph nodes without first going through the lungs.
Overexpressing Temperature-Sensitive Dynamin Decelerates Phototransduction and Bundles Microtubules in Drosophila Photoreceptors

shibirets1, a temperature-sensitive mutation of the Drosophila gene encoding a Dynamin orthologue, blocks vesicle endocytosis and thus synaptic transmission, at elevated, or restrictive temperatures. By targeted Gal4 expression, UAS-shibirets1 has been used to dissect neuronal circuits. We investigated the effects of UAS-shibirets1 overexpression in Drosophila photoreceptors at permissive (19°C) and restrictive (31°C) temperatures. At 19°C, overexpression of UAS-shits1 causes decelerated phototransduction and reduced neurotransmitter release. This phenotype is exacerbated with dark adaptation, age and in white mutants. Photoreceptors overexpressing UAS-shibirets1 contain terminals with widespread vacuolated mitochondria, reduced numbers of vesicles and bundled microtubules. Immuno-electron microscopy reveals that the latter are dynamin coated. Further, the microtubule phenotype is not restricted to photoreceptors, as UAS-shibirets1 overexpression in lamina cells also bundles microtubules. We conclude that dynamin has multiple functions that are interrupted by UAS-shibirets1 overexpression in Drosophila photoreceptors, destabilizing their neural communication irreversibly at previously reported permissive temperatures.
An Evaluation of Microarray Visualization Tools for Biological Insight

High-throughput experiments such as gene expression microarrays in the life sciences result in large datasets. In response, a wide variety of visualization tools have been created to facilitate data analysis. Biologists often face a dilemma in choosing the best tool for their situation. The tool that works best for one biologist may not work well for another due to differences in the type of insight they seek from their data. A primary purpose of a visualization tool is to provide domain-relevant insight into the data. Ideally, any user wants maximum information in the least possible time. In this paper we identify several distinct characteristics of insight that enable us to recognize and quantify it. Based on this, we empirically evaluate five popular microarray visualization tools. Our conclusions can guide biologists in selecting the best tool for their data, and computer scientists in developing and evaluating visualizations
Diverse pollinator communities enhance plant reproductive success

Understanding the functional consequences of biodiversity loss is a major goal of ecology. Animal-mediated pollination is an essential ecosystem function and service provided to mankind. However, little is known how pollinator diversity could affect pollination services. Using a substitutive design, we experimentally manipulated functional group (FG) and species richness of pollinator communities to investigate their consequences on the reproductive success of an obligate out-crossing model plant species, Raphanus sativus. Both fruit and seed set increased with pollinator FG richness. Furthermore, seed set increased with species richness in pollinator communities composed of a single FG. However, in multiple-FG communities, highest species richness resulted in slightly reduced pollination services compared with intermediate species richness. Our analysis indicates that the presence of social bees, which showed roughly four times higher visitation rates than solitary bees or hoverflies, was an important factor contributing to the positive pollinator diversity–pollination service relationship, in particular, for fruit set. Visitation rate at different daytimes, and less so among flower heights, varied among social bees, solitary bees and hoverflies, indicating a niche complementarity among these pollinator groups. Our study demonstrates enhanced pollination services of diverse pollinator communities at the plant population level and suggests that both the niche complementarity and the presence of specific taxa in a pollinator community drive this positive relationship.
Deep Syntactic Processing by Combining Shallow Methods

We present a novel approach for finding discontinuities that outperforms previously published results on this task. Rather than using a deeper grammar formalism, our system combines a simple unlexicalized PCFG parser with a shallow pre-processor. This pre-processor, which we call a trace tagger, does surprisingly well on detecting where discontinuities can occur without using phase structure information.
Intellectual disability and mental health problems: a qualitative study of general practitioners’ views

Objectives To investigate general practitioners’ (GPs) experiences in managing patients with intellectual disabilities (ID) and mental and behavioural problems (MBP). Design Qualitative study using in-depth interviews. Setting General practice in Hedmark county, Norway. Participants 10 GPs were qualitatively interviewed about their professional experience regarding patients with ID and MBP. Data were analysed by all authors using systematic text condensation. Results The participants’ knowledge was primarily experience-based and collaboration with specialists seemed to be individual rather than systemic. The GPs provided divergent attitudes to referral, treatment, collaboration, regular health checks and home visits. Conclusions GPs are in a position to provide evidence-based and individual treatment for both psychological and somatic problems among patients with ID. However, they do not appear to be making use of evidence-based treatment decisions. The GPs feel that they are left alone in decision-making, and find it difficult to find trustworthy collaborative partners. The findings in this study provide useful information for further research in the field.
FATIGUE AND HEALING CHARACTERIZATION OF ASPHALT MIXTURES

This paper investigates the effect of the processes on fatigue fracture and fracture healing during controlled-strain, dynamic mechanical analysis (DMA) testing. Sand asphalt samples were fabricated with two SHRP-classified binders: AAD-1 and AAM-1. DMA testing was performed at 25°C and at 10 Hz. The mechanical response during DMA testing was monitored using three different damage indicators: (1) change in dynamic modulus; (2) change in pseudo stiffness; and (3) change in dissipated strain energy. When either of these parameters are plotted versus the number of load cycles, two inflection points are apparent that define a significant change in sample behavior due to damage. The second inflection point is a reasonable definition of failure, as it is strongly correlated with the peak of the plot of phase angle versus load repetitions. Furthermore, the phase angle drops precipitously at the second inflection point. By performing controlled-strain torsional fatigue tests at three different strain levels, each great enough to induce damage, a reproducible fatigue relationship (number of load cycles as a function of stress level) is developed. The introduction of several rest periods during testing lengthened fatigue life. Successful development of this testing method is suggested as a potential specification-type test method because of its efficiency, reproducibility, and reliability.
Unshrouded Plate Fin Heat Sinks for Electronics Cooling: Validation of a Comprehensive Thermal Model and Cost Optimization in Semi-Active Configuration

Plate Fin Heat Sinks (PFHS) are among the simplest and most widespread devices for electronics cooling. Because of the many design parameters to be considered, developing both cost and thermal effective PFHS is a critical issue. Here, a novel thermal model of PFHS is presented. The model has a broad field of applicability, being comprehensive of the effects of flow bypass, developing boundary layers, fin efficiency and spreading resistance. Experiments are then carried out to validate the proposed thermal model, and its good accuracy is demonstrated. Finally, an optimization methodology based on genetic algorithms is proposed for a cost-effective selection of the design parameters of PFHS, which is particularly effective with semi-active configurations. Such an optimization methodology is then tested on a commercial heat sink, resulting in a possible 53% volume reduction at fixed thermal performances.