Miracle-dz/UniFAR-FTUs huggingface dataset:
Point Spread Function Formation in Plane-Wave Imaging: A Theoretical Approximation in Fourier Migration

The point spread function (PSF) is often analyzed to determine the image quality of an ultrasound system. The formation of PSF is determined by practical factors, such as transducer aperture, element directivity, apodization, pitch, imaging position, and steering angle. Conventional numerical simulations provide an iterative approach to examine those factors’ effects but cannot explain the inherent mechanism of PSF formation. This article presents a theoretical approximation of PSF formation for plane-wave imaging throughout the Fourier-based reconstruction process. Aforementioned factors are incorporated in the theory. The proposed theory is used to analyze the effects of those factors and presents a high degree of consistency with numerical simulations and experiments.
Mapping Cellular Microenvironments: Proximity Labeling and Complexome Profiling (Seventh Symposium of the Göttingen Proteomics Forum)

Mass spectrometry-based proteomics methods are finding increasing use in structural biology research. Beyond simple interaction networks, information about stable protein-protein complexes or spatially proximal proteins helps to elucidate the biological functions of proteins in a wider cellular context. To shed light on new developments in this field, the Göttingen Proteomics Forum organized a one-day symposium focused on complexome profiling and proximity labeling, two emerging technologies that are gaining significant attention in biomolecular research. The symposium was held in Göttingen, Germany on 23 May, 2019, as part of a series of regular symposia organized by the Göttingen Proteomics Forum.
Cooperative Cellular Uptake and Activity of Octaarginine Antisense Peptide Nucleic Acid (PNA) Conjugates

Cellular uptake and antisense activity of d-octaarginine conjugated peptide nucleic acids (PNAs) is shown to exhibit pronounced cooperativity in serum-containing medium, in particular by being enhanced by analogous mis-match PNA–cell-penetrating peptide (PNA–CPP) conjugates without inherent antisense activity. This cooperativity does not show cell or PNA sequence dependency, suggesting that it is a common effect in cationic CPP conjugated PNA delivery. Interestingly, our results also indicate that Deca-r8-PNA and r8-PNA could assist each other and even other non-CPP PNAs as an uptake enhancer agent. However, the peptide itself (without being attached to the PNA) failed to enhance uptake and antisense activity. These results are compatible with an endosomal uptake mechanism in which the endocytosis event is induced by multiple CPP–PNA binding to the cell surface requiring a certain CPP density, possibly in terms of nanoparticle number and/or size, to be triggered. In particular the finding that the number of endosomal events is dependent on the total CPP–PNA concentration supports such a model. It is not possible from the present results to conclude whether endosomal escape is also cooperatively induced by CPP–PNA.
Cost-Aware Robust Control of Signed Networks by Using a Memetic Algorithm

The robust controllability (RC) of a complex system tries to select a set of dominating entities for the functional control of this entire system without uncertain disturbances, and the research on RC will help to understand the system’s underlying functions. In this article, we introduce the control cost in signed networks and present a cost-aware robust control (CRC) problem in this scenario. The aim of CRC is to minimize the cost to control a set of dominating nodes and transform a set of unbalanced links into balanced ones, such that the signed network can be robustly controlled without uncertain unbalanced factors (like nodes and links). To solve this problem, we first model CRC as a constrained combination optimization problem, and then present a memetic algorithm with some problem-specific knowledge (like the neighbors of nodes, the constraints of CRC, and the fast computation of the cost under each optimization) to solve this problem on signed networks. The extensive experiments on both real social and biological networks assess that our algorithm outperforms several state-of-the-art RC algorithms.
Binding-induced folding under unfolding conditions: Switching between induced fit and conformational selection mechanisms

The chemistry of protein–ligand binding is the basis of virtually every biological process. Ligand binding can be essential for a protein to function in the cell by stabilizing or altering the conformation of a protein, particularly for partially or completely unstructured proteins. However, the mechanisms by which ligand binding impacts disordered proteins or influences the role of disorder in protein folding is not clear. To gain insight into this question, the mechanism of folding induced by the binding of a Pro-rich peptide ligand to the SH3 domain of phosphatidylinositol 3-kinase unfolded in the presence of urea has been studied using kinetic methods. Under strongly denaturing conditions, folding was found to follow a conformational selection (CS) mechanism. However, under mildly denaturing conditions, a ligand concentration–dependent switch in the mechanism was observed. The folding mechanism switched from being predominantly a CS mechanism at low ligand concentrations to being predominantly an induced fit (IF) mechanism at high ligand concentrations. The switch in the mechanism manifests itself as an increase in the reaction flux along the IF pathway at high ligand concentrations. The results indicate that, in the case of intrinsically disordered proteins too, the folding mechanism is determined by the concentration of the ligand that induces structure formation.
A novel non-sense and inactivating variant of ST3GAL3 in two infant siblings suffering severe epilepsy and expressing circulating CA19.9.

Three missense variants of ST3GAL3 are known to be responsible for a congenital disorder of glycosylation determining a neurodevelopmental disorder (intellectual disability/epileptic encephalopathy). Here we report a novel non-sense variant, p.Y220*, in two di-chorionic infant twins presenting a picture of epileptic encephalopathy with impaired neuromotor development. Upon expression in HEK-293T cells, the variant appears totally devoid of enzymatic activity in vitro, apparently accumulated with respect to the wild type or the missense variants, as detected by western blot, and in large part properly localized in the Golgi apparatus, as assessed by confocal microscopy. Both patients were found to efficiently express the CA19.9 antigen in the serum despite the total loss of ST3GAL3 activity, which thus appears replaceable from other ST3GALs in the synthesis of the sialyl-Lewis a epitope. Kinetic studies of ST3GAL3 revealed a strong preference for lactotetraosylceramide as acceptor, and gangliotetraosylceramide was also efficiently utilized in vitro. Moreover, the p.A13D missense variant, the one maintaining residual sialyltransferase activity, was found to have much lower affinity for all suitable substrates than the wild type enzyme, with an overall catalytic efficiency almost negligible. Altogether the present data suggest that the apparent redundancy of ST3GALs deduced from knock-out mouse models only partially exists in humans. In fact, our patients lacking ST3GAL3 activity synthesize the CA19.9 epitope sialyl-Lewis a, but not all glycans necessary for fine brain functions, where the role of minor gangliosides deserves further attention.
Long noncoding RNA PTENP1 affects the recovery of spinal cord injury by regulating the expression of miR‐19b and miR‐21

Exosomes derived from differentiated P12 cells and MSCs were proved to suppress apoptosis of neuron cells, and phosphatase and tensin homolog pseudogene 1 (PTENP1) was reported to inhibit cell proliferation. In this study, we aimed to investigate the role of PTENP1 in the process of post‐spinal cord injury (SCI) recovery, so as to evaluate the therapeutic effects of exosomes derived from MSCs transfected with PTENP1 short hairpin RNA (shRNA), as a type of novel biomarkers in the treatment of SCI. Electron microscopy was used to observe the morphology of different exosomes. Real‐time polymerase chain reaction and western blot, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays, flow cytometry, Nissl staining, immunohistochemistry assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were conducted to investigate and validate the underlying molecular signaling pathway. PTENP1‐shRNA downregulated PTENP1 and PTEN while upregulating miR‐21 and miR‐19b. PTENP1‐shRNA also accelerated cell apoptosis and reduced cell viability. In addition, PTENP1 reduced the miR‐21 and miR‐19b expression by directly targeting miR‐21 and miR‐19b. Meanwhile, both miR‐21 and miR‐19b reduced the expression of PTEN by directly targeting the 3′‐untranslated region of PTEN. Furthermore, PTEN level and apoptosis index of neuron cells was the highest in the SCI group, while the treatment with exosomes+PTENP1‐shRNA reduced the PTEN expression to a level similar to that in the sham group. Finally, PTENP1 inhibited miR‐21 and miR‐19b expression but upregulated PTEN expression. The upregulation of miR‐21/miR‐19b also suppressed the apoptosis of neuron cells by downregulating the PTEN expression. PTENP1 is involved in the recovery of SCI by regulating the expression of miR‐19b and miR‐21, and exosomes from PTENP1‐shRNA‐transfected cells may be used as a novel biomarker in SCI treatment.
Molecular Carcinogenesis

Supriyo Chakraborty, Department of Biotechnology, Assam University, Silchar 788011, Assam, India. Email: supriyoch_2008@rediffmail.com Abstract Tumor suppressor genes encode different proteins that inhibit the uncontrolled proliferation of cell growth and tumor development. To acquire clues for predicting gene expression level, it is essential to understand the codon usage bias (CUB) of genes to characterize genome which possesses its own compositional characteristics and unique coding sequences. We used bioinformatic tools to analyze the codon usage patterns of 637 human tumor suppressor genes as no work was reported earlier. The mean effective number of codons of these genes was 48, indicating low CUB. Our results exhibited a significant positive correlation among different nucleotide compositions and the codons ending with C base was most frequently used along with the most over‐represented codon CTG and GTG codifying leucine and valine amino acid, respectively, in human tumor suppressor genes. The neutrality plot showed a significant positive correlation (Pearson, r = 0. 646; P < .01) suggesting that mutation on GC bias might affect the CUB. However, the linear regression coefficient of GC12 on GC3 in human tumor suppressor genes suggested that natural selection played a major role while mutation pressure played a minor role in the codon usage patterns of tumor suppressor genes in human. Our study would throw light into the factors that affect CUB and the codon usage patterns in the human tumor suppressor genes.
Climate change shifts natural selection and the adaptive potential of the perennial forb Boechera stricta in the Rocky Mountains

Heritable genetic variation is necessary for populations to evolve in response to anthropogenic climate change. However, antagonistic genetic correlations among traits may constrain the rate of adaptation, even if substantial genetic variation exists. We examine potential genetic responses to selection by comparing multivariate genetic variance–covariances of traits and fitness (multivariate Robertson–Price identities) across different environments in a reciprocal transplant experiment of the forb Boechera stricta in the Rocky Mountains. By transplanting populations into four common gardens arrayed along an elevational gradient, and exposing populations to control and snow removal treatments, we simulated future and current climates and snowmelt regimes. Genetic variation in flowering and germination phenology declined in plants moved downslope to warmer, drier sites, suggesting that these traits may have a limited ability to evolve under future climates. Simulated climate change via snow removal altered the strength of selection on flowering traits, but we found little evidence that genetic correlations among traits are likely to affect the rate of adaptation to climate change. Overall, our results suggest that climate change may alter the evolutionary potential of B. stricta, but reduced expression of genetic variation may be a larger impediment to adaptation than constraints imposed by antagonistic genetic correlations.
Unintended Consequences: Review of New Artifacts Introduced by Iterative Reconstruction CT Metal Artifact Reduction in Spine Imaging

SUMMARY: Metal hardware serves as a common artifact source in spine CT imaging in the form of beam-hardening, photon starvation, and streaking. Postprocessing metal artifact reduction techniques have been developed to decrease these artifacts, which has been proved to improve visualization of soft-tissue structures and increase diagnostic confidence. However, metal artifact reduction reconstruction introduces its own novel artifacts that can mimic pathology.
Toward Dynamically Adaptive Simulation: Multimodal Classification of User Expertise Using Wearable Devices

Simulation-based training has been proven to be a highly effective pedagogical strategy. However, misalignment between the participant’s level of expertise and the difficulty of the simulation has been shown to have significant negative impact on learning outcomes. To ensure that learning outcomes are achieved, we propose a novel framework for adaptive simulation with the goal of identifying the level of expertise of the learner, and dynamically modulating the simulation complexity to match the learner’s capability. To facilitate the development of this framework, we investigate the classification of expertise using biological signals monitored through wearable sensors. Trauma simulations were developed in which electrocardiogram (ECG) and galvanic skin response (GSR) signals of both novice and expert trauma responders were collected. These signals were then utilized to classify the responders’ expertise, successive to feature extraction and selection, using a number of machine learning methods. The results show the feasibility of utilizing these bio-signals for multimodal expertise classification to be used in adaptive simulation applications.
The International Genome Sample Resource (IGSR) collection of open human genomic variation resources

Abstract To sustain and develop the largest fully open human genomic resources the International Genome Sample Resource (IGSR) (https://www.internationalgenome.org) was established. It is built on the foundation of the 1000 Genomes Project, which created the largest openly accessible catalogue of human genomic variation developed from samples spanning five continents. IGSR (i) maintains access to 1000 Genomes Project resources, (ii) updates 1000 Genomes Project resources to the GRCh38 human reference assembly, (iii) adds new data generated on 1000 Genomes Project cell lines, (iv) shares data from samples with a similarly open consent to increase the number of samples and populations represented in the resources and (v) provides support to users of these resources. Among recent updates are the release of variation calls from 1000 Genomes Project data calculated directly on GRCh38 and the addition of high coverage sequence data for the 2504 samples in the 1000 Genomes Project phase three panel. The data portal, which facilitates web-based exploration of the IGSR resources, has been updated to include samples which were not part of the 1000 Genomes Project and now presents a unified view of data and samples across almost 5000 samples from multiple studies. All data is fully open and publicly accessible.
Dynamics of the microbial community during growth of the house dust mite Dermatophagoides farinae in culture.

The variation in house dust mite microbial communities is important because various microorganisms modulate the production of allergens by their mite hosts and/or contaminate immunotherapeutic extracts. Temporal changes in mite microbiomes and the mite culture environment occurring at different stages of mite culture development are particularly understudied in this system. Here, we analyzed the dynamics of microbial communities during the culture growth of Dermatophagoides farinae. Changes in microbiomes were related to three key variables: the mite population density, microbial microcosm respiration, and concentration of guanine (the mite nitrogenous waste metabolite). Mite populations exhibited the following phases: exponential growth, plateau, and exponential decline. The intracellular bacterium Cardinium and the yeast Saccharomyces cerevisiae prevailed in the internal mite microbiomes, and the bacterium Lactobacillus fermentum was prevalent in the mite diet. The reduction in the mite population size during the late phases of culture development was related to the changes in their microbial profiles: the intracellular bacterium Cardinium was replaced by Staphylococcus, Oceanobacillus and Virgibacillus, and S. cerevisiae was replaced by the antagonistic fungi Aspergillus penicillioides and Candida. Increases in the guanine content were positively correlated with increases in the Staphylococcus and A. penicillioides profiles in the culture environment. Our results show that the mite microbiome exhibits strong, dynamic alterations in its profiles across different mite culture growth stages.
" Brain Invaders": a prototype of an open-source P300-based video game working with the OpenViBE platform

We have developed the prototype of a pure-BCI video game based on the well known vintage video game "Space Invaders". In our "Brain Invaders" a number of aliens are displayed in a grid and the player has to destroy a particular alien, the target, only by concentrating on it. The game makes use of a stateof- the art P300 oddball paradigm to select the alien to be destroyed at a regular pace, based on current probabilities assigned to each alien by a learning machine continuously analyzing and classifying the user's electroencephalographic stream (the Open-ViBE platform). As compared to the standard P300- speller paradigm our game may optionally use: 1) flashing items in random groups and no longer by rows and columns; 2) variable inter-stimulus intervals drawn from an exponential distribution; 3) magnification of flashed target items. Preliminary tests show an excellent transfer rate, since starting with 36 aliens on the screen, one to three repetitions typically suffice to destroy the target alien. Our development is completely open-source and will continue to improve further the signal processing and classification algorithms, besides the paradigm itself, the gameplay and the BCI ergonomy, in order to achieve a "Plug & Play" video game suitable for the large public of gamers.
Melatonin long‐lasting beneficial effects on pulmonary vascular reactivity and redox balance in chronic hypoxic ovine neonates

Pulmonary arterial hypertension of the neonate (PAHN) is a pathophysiological condition characterized by maladaptive pulmonary vascular remodeling and abnormal contractile reactivity. This is a multifactorial syndrome with chronic hypoxia and oxidative stress as main etiological drivers, and with limited effectiveness in therapeutic approaches. Melatonin is a neurohormone with antioxidant and vasodilator properties at the pulmonary level. Therefore, this study aims to test whether a postnatal treatment with melatonin during the neonatal period improves in a long‐lasting manner the clinical condition of PAHN. Ten newborn lambs gestated and born at 3600 m were used in this study, five received vehicle and five received melatonin in daily doses of 1 mg kg−1 for the first 3 weeks of life. After 1 week of treatment completion, lung tissue and small pulmonary arteries (SPA) were collected for wire myography, molecular biology, and morphostructural analyses. Melatonin decreased pulmonary arterial pressure the first 4 days of treatment. At 1 month old, melatonin decreased the contractile response to the vasoconstrictors K+, TX2, and ET‐1. Further, melatonin increased the endothelium‐dependent and muscle‐dependent vasodilation of SPA. Finally, the treatment decreased pulmonary oxidative stress by inducing antioxidant enzymes and diminishing pro‐oxidant sources. In conclusion, melatonin improved vascular reactivity and oxidative stress at the pulmonary level in PAHN lambs gestated and born in chronic hypoxia.
System Attributes that Influence Reported Improvement in Drivers’ Experiences with Adaptive Cruise Control and Active Lane Keeping after Daily Use in Five Production Vehicles

ABSTRACT Driving automation technology must be used to benefit safety, but little is known about real-world experiences with the technology. Fifty-one Insurance Institute for Highway Safety employees used an Audi A4 or Qty 7, Honda Civic, Infiniti QX60, or Toyota Prius for up to several weeks and completed surveys about their experiences. Each vehicle had adaptive cruise control (ACC), and the Audis and Honda had active lane keeping (ALK). Drivers agreed ACC improved the driving experience more than ALK, but this was not true for all vehicles. Drivers were most comfortable using automation on interstates, and least comfortable using ACC on local roads and ALK on curvy roads. Increased agreement that the technology made gentle, smooth changes to vehicle control predicted increased agreement that it improved the driving experience. Designers should implement automation that makes smooth and gentle changes to steering or speed to improve perceptions of the technology and encourage use.
Work ability, functional exercise capacity and prevalence of obesity in perimenopausal and postmenopausal women with non-manual employment

Objective. This study aimed to evaluate work ability and functional exercise capacity, and their correlation to each other and to obesity, in perimenopausal and postmenopausal women with non-manual employment. Materials and methods. The study included 300 women aged 44–66 years. The following measures were used: work ability index (WAI), 6-min walk test (6MWT), body mass index (BMI), waist–hip ratio (WHR) and adipose tissue accumulation. Regression models of the WAI and distance in the 6MWT were estimated. Results. The examined women obtained WAI 39.0 ± 5.0, BMI 26.2 ± 4.6, WHR 0.819 ± 0.060 and adipose tissue accumulation 30.1 ± 6.1%, on average. About 19% of women obtained a very good work ability score, 55% good, 23% medium and 3% poor. About 17% of women were obese, 39% overweight and 44% normal body mass, 29% had abdominal obesity, 19% had elevated accumulation of adipose tissue and 21% had high accumulation of adipose tissue. These results did not differ significantly between perimenopausal and postmenopausal women The postmenopausal women obtained a significantly lower functional exercise capacity score than perimenopausal women. Conclusion. Work ability correlates positively to functional exercise capacity, which correlates negatively to adipose tissue accumulation in perimenopausal women with non-manual employment, but not in postmenopausal cases.