Miracle-dz/UniFAR-FTUs huggingface dataset:
Resolution and super‐resolution

Many papers have claimed the attainment of super‐resolution, i.e. resolution beyond that achieved classically, by measurement of the profile of a feature in the image. We argue that measurement of the contrast of the image of a dark bar on a bright background does not give a measure of resolution, but of detection sensitivity. The width of a bar that gives an intensity at the center of the bar of 0.735 that in the bright region (the same ratio as in the Rayleigh resolution criterion) is λ/(13.9×numerical aperture) for the coherent case with central illumination. This figure, which compares with λ/(numerical aperture) for the Abbe resolution limit with central illumination, holds for the classical case, and so is no indication of super‐resolution. Theoretical images for two points, two lines, arrays of lines, arrays of bars, and grating objects are compared. These results can be used a reference for experimental results, to determine if super‐resolution has indeed been attained. The history of the development of the theory of microscope resolution is outlined.
Sorafenib inhibits cell growth but fails to enhance radio- and chemosensitivity of glioblastoma cell lines

Background Glioblastomas (GBM) are the most common malignant type of primary brain tumor. GBM are intensively treated with surgery and combined radiochemotherapy using X-irradiation and temozolomide (TMZ) but they are still associated with an extremely poor prognosis, urging for the development of new treatment strategies. To improve the outcome of GBM patients, the small molecule multi-kinase inhibitor sorafenib has moved into focus of recent research. Sorafenib has already been shown to enhance the radio- and radiochemosensitivity of other tumor entities. Whether sorafenib is also able to sensitize GBM cells to radio- and chemotherapy is still an unsolved question which we have addressed in this study. Methods The effect of sorafenib on signaling, proliferation, radiosensitivity, chemosensitivity and radiochemosensitivity was analyzed in six glioblastoma cell lines using Western blot, proliferation- and colony formation assays. Results In half of the cell lines sorafenib clearly inhibited MAPK signaling. We also observed a strong blockage of proliferation, which was, however, not associated with MAPK pathway inhibition. Sorafenib had only minor effects on cell survival when administered alone. Most importantly, sorafenib treatment failed to enhance GBM cell killing by irradiation, TMZ or combined treatment, and instead rather caused resistance in some cell lines. Conclusion Our data suggest that sorafenib treatment may not improve the efficacy of radiochemotherapy in GBM.
Differential Regulation of Cryptic Genetic Variation Shapes the Genetic Interactome Underlying Complex Traits

Cryptic genetic variation (CGV) refers to genetic variants whose effects are buffered in most conditions but manifest phenotypically upon specific genetic and environmental perturbations. Despite having a central role in adaptation, contribution of CGV to regulation of quantitative traits is unclear. Instead, a relatively simplistic architecture of additive genetic loci is known to regulate phenotypic variation in most traits. In this paper, we investigate the regulation of CGV and its implication on the genetic architecture of quantitative traits at a genome-wide level. We use a previously published dataset of biparental recombinant population of Saccharomyces cerevisiae phenotyped in 34 diverse environments to perform single locus, two-locus, and covariance mapping. We identify loci that have independent additive effects as well as those which regulate the phenotypic manifestation of other genetic variants (variance QTL). We find that whereas additive genetic variance is predominant, a higher order genetic interaction network regulates variation in certain environments. Despite containing pleiotropic loci, with effects across environments, these genetic networks are highly environment specific. CGV is buffered under most allelic combinations of these networks and perturbed only in rare combinations resulting in high phenotypic variance. The presence of such environment specific genetic networks is the underlying cause of abundant gene–environment interactions. We demonstrate that overlaying identified molecular networks on such genetic networks can identify potential candidate genes and underlying mechanisms regulating phenotypic variation. Such an integrated approach applied to human disease datasets has the potential to improve the ability to predict disease predisposition and identify specific therapeutic targets.
Reduced Effective Emotion Regulation in Night Owls

Previous research has demonstrated a clear link between late chronotype and depression. The vulnerability factors underpinning this link, however, are unclear. Here the relationship between two specific emotion regulation strategies, cognitive reappraisal and expressive suppression, and chronotype was investigated using multiple regression. Two hundred and forty participants (age range 18-80, 189 females) completed validated self-report questionnaires assaying chronotype, neuroticism, depressive symptomatology, sleep quality, and emotion regulation. Eveningness was associated with increased expressive suppression, and morningness was associated with increased cognitive reappraisal after controlling for age, gender, depressive symptomatology, neuroticism, and sleep quality. Trait expressive suppression and reduced cognitive reappraisal are known to increase depression risk. Our results suggest that eveningness is associated with impaired emotion regulation, which may confer risk for future depression. These findings suggest modifiable markers that could be therapeutically targeted to prevent the onset of depression in late chronotype individuals.
Copper Containing Coatings for Metallized Textile Fabrics

Copper Containing Coatings for Metallized Textile Fabrics Compared to silver modified textiles, textiles modified with copper components are less prominently mentioned in literature. Therefore, the aim of the now presented paper is to present an overview on different copper functionalized textiles. For this presentation, two types of fabrics are taken into account – commercially available copper plated polyamide and textiles coated with copper containing effect pigments. The surface properties and the composition of those materials are presented in detail. Optical properties are determined in the arrangements of diffuse reflection and diffuse transmission for UV-, visible- and IR-light. Hints on probable applications in the fields of radiation protection are reported.
Host Coenzyme Q Redox State Is an Early Biomarker of Thermal Stress in the Coral Acropora millepora

Bleaching episodes caused by increasing seawater temperatures may induce mass coral mortality and are regarded as one of the biggest threats to coral reef ecosystems worldwide. The current consensus is that this phenomenon results from enhanced production of harmful reactive oxygen species (ROS) that disrupt the symbiosis between corals and their endosymbiotic dinoflagellates, Symbiodinium. Here, the responses of two important antioxidant defence components, the host coenzyme Q (CoQ) and symbiont plastoquinone (PQ) pools, are investigated for the first time in colonies of the scleractinian coral, Acropora millepora, during experimentally-induced bleaching under ecologically relevant conditions. Liquid chromatography-mass spectrometry (LC-MS) was used to quantify the states of these two pools, together with physiological parameters assessing the general state of the symbiosis (including photosystem II photochemical efficiency, chlorophyll concentration and Symbiodinium cell densities). The results show that the responses of the two antioxidant systems occur on different timescales: (i) the redox state of the Symbiodinium PQ pool remained stable until twelve days into the experiment, after which there was an abrupt oxidative shift; (ii) by contrast, an oxidative shift of approximately 10% had occurred in the host CoQ pool after 6 days of thermal stress, prior to significant changes in any other physiological parameter measured. Host CoQ pool oxidation is thus an early biomarker of thermal stress in corals, and this antioxidant pool is likely to play a key role in quenching thermally-induced ROS in the coral-algal symbiosis. This study adds to a growing body of work that indicates host cellular responses may precede the bleaching process and symbiont dysfunction.
C1q/TNF-related protein-1: an adipokine marking and promoting atherosclerosis.

AIMS We investigated the association of the adipokine C1q/TNF-related protein (CTRP) 1 with coronary artery disease (CAD), and the biological vascular effects of CTRP1. METHODS AND RESULTS We analysed CTRP1 levels in sera of CAD patients (n = 451) and non-CAD controls (n = 686), and in coronary endarterectomy specimens (n = 32), non-atherosclerotic internal mammary arteries (n = 26), aortic atherosclerotic plaques (n = 15), and non-atherosclerotic aortic samples (n = 10). C1q/TNF-related protein-levels were higher in sera, endarterectomy specimens, aortic atherosclerotic plaques, and peripheral blood mononuclear cells (PBMCs) from CAD patients compared with controls, and were related to CAD severity. The production of CTRP1 was profusely induced by inflammatory cytokines and itself caused a concentration-dependent expression of adhesion molecules and inflammatory markers in human endothelial cells, human peripheral blood monocytes, and THP-1 cells. C1q/TNF-related protein-1 induced p38-dependent monocyte-endothelium adhesion in vitro and the recruitment of leucocytes to mesenteric venules in C57BL/6 mice. Immunohistochemistry of atherosclerotic femoral arteries exhibited CD68 and VE-cadherin loci-associated increased CTRP1 expression in plaques. Compared with saline, intraperitoneal injection of recombinant CTRP1 protein (200 μg/kg) every other day promoted atherogenesis in apoE(-/-) mice at 24 weeks. However, pro-atherogenic effects were significantly attenuated in CTRP1(-/-)/apoE(-/-) double-knockout mice compared with apoE(-/-) mice, with a consistent decrease in vascular adhesion molecule, phospho-p38 and TNF-α expression and macrophage infiltration in plaque in CTRP1(-/-) and double-knockout mice. Tumour necrosis factor-α-induced expression of adhesion molecules and cytokines were lower in primary endothelial cells and macrophages from CTRP(-/-) mice than in those from C57BL/6 mice. CONCLUSION C1q/TNF-related protein-1 is a marker of atherosclerosis in humans and promotes atherogenesis in mice.
Multi-Contextual Segregation and Environmental Justice Research: Toward Fine-Scale Spatiotemporal Approaches

Many environmental justice studies have sought to examine the effect of residential segregation on unequal exposure to environmental factors among different social groups, but little is known about how segregation in non-residential contexts affects such disparity. Based on a review of the relevant literature, this paper discusses the limitations of traditional residence-based approaches in examining the association between socioeconomic or racial/ethnic segregation and unequal environmental exposure in environmental justice research. It emphasizes that future research needs to go beyond residential segregation by considering the full spectrum of segregation experienced by people in various geographic and temporal contexts of everyday life. Along with this comprehensive understanding of segregation, the paper also highlights the importance of assessing environmental exposure at a high spatiotemporal resolution in environmental justice research. The successful integration of a comprehensive concept of segregation, high-resolution data and fine-grained spatiotemporal approaches to assessing segregation and environmental exposure would provide more nuanced and robust findings on the associations between segregation and disparities in environmental exposure and their health impacts. Moreover, it would also contribute to significantly expanding the scope of environmental justice research.
Photonic and Plasmonic Nanotweezing of Nano- and Microscale Particles

The ability to manipulate and sense biological molecules is important in many life science domains, such as single-molecule biophysics, the development of new drugs and cancer detection. Although the manipulation of biological matter at the nanoscale continues to be a challenge, several types of nanotweezers based on different technologies have recently been demonstrated to address this challenge. In particular, photonic and plasmonic nanotweezers are attracting a strong research effort especially because they are efficient and stable, they offer fast response time, and avoid any direct physical contact with the target object to be trapped, thus preventing its disruption or damage. In this paper, we critically review photonic and plasmonic resonant technologies for biomolecule trapping, manipulation, and sensing at the nanoscale, with a special emphasis on hybrid photonic/plasmonic nanodevices allowing a very strong light–matter interaction. The state-of-the-art of competing technologies, e.g., electronic, magnetic, acoustic and carbon nanotube-based nanotweezers, and a description of their applications are also included.
Defective Apoptosis in Intestinal and Mesenteric Adipose Tissue of Crohn’s Disease Patients

Background Crohn’s disease (CD) is associated with complex pathogenic pathways involving defects in apoptosis mechanisms. Recently, mesenteric adipose tissue (MAT) has been associated with CD ethiopathology, since adipose thickening is detected close to the affected intestinal area. However, the potential role of altered apoptosis in MAT of CD has not been addressed. Aims To evaluate apoptosis in the intestinal mucosa and MAT of patients with CD. Methods Samples of intestinal mucosa and MAT from patients with ileocecal CD and from non-inflammatory bowel diseases patients (controls) were studied. Apoptosis was assessed by TUNEL assay and correlated with the adipocytes histological morphometric analysis. The transcriptional and protein analysis of selected genes and proteins related to apoptosis were determined. Results TUNEL assay showed fewer apoptotic cells in CD, when compared to the control groups, both in the intestinal mucosa and in MAT. In addition, the number of apoptotic cells (TUNEL) correlated significantly with the area and perimeter of the adipose cells in MAT. Transcriptomic and proteomic analysis reveal a significantly lower transcript and protein levels of Bax in the intestinal mucosa of CD, compared to the controls; low protein levels of Bax were found localized in the lamina propria and not in the epithelium of this tissue. Furthermore, higher level of Bcl-2 and low level of Caspase 3 were seen in the MAT of CD patients. Conclusion The defective apoptosis in MAT may explain the singular morphological characteristics of this tissue in CD, which may be implicated in the pathophysiology of the disease.
Expression of Matrix Metalloproteinases-2/-9 is Associated With Microvessel Density in Pancreatic Cancer

This study aimed to investigate the association of matrix-metalloproteinase (MMP)-2 and MMP-9 with microvessel density (MVD) in pancreatic cancer. The tumor tissues and para-tumor tissues of 30 patients with pancreatic cancer were pathologically examined. The normal pancreatic tissues of another 17 patients served as controls. The expression of MMP-2 and MMP-9 was examined using immunohistochemistry and scored. The association of MMP-2 and MMP-9 with the MVD values and pathological features were analyzed. The positive expression rates of MMP-2 and MMP-9 in the tumor tissues were significantly higher than those in the para-tumor tissues (P < 0.01). In normal pancreatic tissues, both MMP-2 and MMP-9 expressions were negative. The MVD values increased significantly along with higher tumor node metastasis stages (P = 0.04). The MVD values were positively correlated with MMP-2 scores (r = 0.563, P < 0.05) and MMP-9 scores (r = 0.451, P < 0.05). The expression of MMP-2 and MMP-9 is associated with angiogenesis in pancreatic cancer. MMPs might be used as prognostic factors and therapy targets for patients with pancreatic cancer.
Optogenetics in cancer drug discovery

ABSTRACT Introduction: The discovery and domestication of biomolecules that respond to light has taken a light of its own, providing new molecular tools with incredible spatio-temporal resolution to manipulate cellular behavior. Areas covered: The authors herein analyze the current optogenetic tools in light of their current, and potential, uses in cancer drug discovery, biosafety and cancer biology. Expert opinion: The pipeline from drug discovery to the clinic is plagued with drawbacks, where most drugs fail in either efficacy or safety. These issues require the redesign of the pipeline and the development of more controllable/personalized therapies. Light is, aside from inexpensive, almost harmless if used appropriately, can be directed to single cells or organs with controllable penetration, and comes in a variety of wavelengths. Light-responsive systems can activate, inhibit or compensate cell signaling pathways or specific cellular events, allowing the specific control of the genome and epigenome, and modulate cell fate and transformation. These synthetic molecular tools have the potential to revolutionize drug discovery and cancer research.
Accuracy of Visual Scoring and Semi-Quantification of Ultrasound Strain Elastography – A Phantom Study

Purpose The aim of this study was to evaluate the performance of strain elastography in an elasticity phantom and to assess which factors influenced visual scoring, strain histograms and strain ratios. Furthermore this study aimed to evaluate the effect of observer experience on visual scorings. Materials and Methods Two operators examined 20 targets of various stiffness and size (16.7 to 2.5 mm) in an elasticity phantom at a depth of 3.5 cm with a 5–18 MHz transducer. Two pre-settings were used yielding 80 scans. Eight evaluators, four experienced, four inexperienced, performed visual scorings. Cut-offs for semi-quantitative methods were established for prediction of target stiffness. Data was pooled in two categories allowing calculations of sensitivity and specificity. Statistical tests chi-square test and linear regression as relevant. Results Strain ratios and strain histograms were superior to visual scorings of both experienced and inexperienced observers (p = 0.025, strain histograms vs. experienced observers, p<0.001, strain histograms vs. inexperienced observers, p = 0.044 strain ratios vs. experienced observers and p = 0.002 strain ratios vs. inexperienced observers). No significant difference in predicting target stiffness between strain ratios and strain histograms (p = 0.83) nor between experienced and inexperienced observers (p = 0.054) was shown when using four categories. When pooling data in two groups (80 kPa/45 kPa vs. 14/8 kPa) the difference between the observers became significant (p<0.001). Target size had a significant influence on strain ratios measurements (p = 0.017) and on visual scorings (p<0.001) but not on the strain histograms(p = 0.358). Observer experience had significant effect on visual scorings(p = 0.003). Conclusion Strain ratios and strain histograms are superior to visual scoring in assessing target stiffness in a phantom. Target size had a significant impact on strain ratios and visual scoring, but not on strain histograms. Experience influenced visual scorings but the difference between experienced and inexperienced observers was only significant when looking at two classes of target stiffness.
Meta‐analysis of Gaussian individual patient data: Two‐stage or not two‐stage?

Quantitative evidence synthesis through meta‐analysis is central to evidence‐based medicine. For well‐documented reasons, the meta‐analysis of individual patient data is held in higher regard than aggregate data. With access to individual patient data, the analysis is not restricted to a “two‐stage” approach (combining estimates and standard errors) but can estimate parameters of interest by fitting a single model to all of the data, a so‐called “one‐stage” analysis. There has been debate about the merits of one‐ and two‐stage analysis. Arguments for one‐stage analysis have typically noted that a wider range of models can be fitted and overall estimates may be more precise. The two‐stage side has emphasised that the models that can be fitted in two stages are sufficient to answer the relevant questions, with less scope for mistakes because there are fewer modelling choices to be made in the two‐stage approach. For Gaussian data, we consider the statistical arguments for flexibility and precision in small‐sample settings. Regarding flexibility, several of the models that can be fitted only in one stage may not be of serious interest to most meta‐analysis practitioners. Regarding precision, we consider fixed‐ and random‐effects meta‐analysis and see that, for a model making certain assumptions, the number of stages used to fit this model is irrelevant; the precision will be approximately equal. Meta‐analysts should choose modelling assumptions carefully. Sometimes relevant models can only be fitted in one stage. Otherwise, meta‐analysts are free to use whichever procedure is most convenient to fit the identified model.
Immobilized metal affinity chromatography optimized for the analysis of extracellular phosphorylation

Phosphorylation is the most widely studied posttranslational modification. Its role within the cell has been the focus of numerous large‐scale studies. Recently there is growing evidence on the biological significance of extracellular phosphorylation. The analysis of these phosphopeptides is complicated by the abundance of glycosylation in the extracellular space, since glycopeptides are also enriched by the methods used for phosphopeptide isolation. Thus, we optimized IMAC for phosphorylation analysis of secreted proteins, specifically in human serum. Selectivity and efficiency of different enrichment conditions used in earlier large‐scale phosphoproteomic studies were evaluated. We found that minimizing hydrophilic interactions in the enrichment allowed selective phosphopeptide isolation. Using a two‐step IMAC enrichment protocol under these conditions led to the identification of ∼100 phosphorylation sites from the tryptic digest of as little as 40 μL human serum.
Weight status, fatness and body image perception of North African immigrant women in Italy

Abstract Objective To investigate the nutritional status of North African (NA) immigrant women in Italy, analysing their body size, adiposity and body image perception in comparison to Italian natives and NA residents. Design The study utilized a cross-sectional design. Anthropometric traits were directly measured and a few indices were computed as proxy measures of nutritional status and adiposity. Body image perception was assessed using silhouette drawings. ANCOVA, adjusted for age, was used to compare anthropometric traits among different groups of women and the χ 2 test to analyse differences in the prevalence of nutritional status. Setting Italy and North Africa (Tunisia, Morocco). Subjects A sample of 433 women aged 18–60 years old: NA immigrants (n 105); Italians (n 100); Tunisians (n 104); Moroccans (n 124). Results Overweight/obesity prevalence was very high in immigrants (79·8 %). Immigrants had the highest BMI value, the greatest hip circumference and mid upper-arm circumference. Their triceps skinfold thickness was significantly higher than that of Italians, but lower than that of NA residents. Conclusions NA immigrant women in Italy showed a higher incidence of overweight compared with Italians and NA residents. All groups showed a preference for a thinner body in comparison to their actual bodies and the immigrants are the most dissatisfied. Immigrants remain a high-risk group for obesity. Assessment of their body composition and health risk profile should be improved by using specific anthropometric measures that are easy to collect even in the case of large migration flows.