Miracle-dz/UniFAR-FTUs huggingface dataset:
Precise spatial restriction of BMP signaling in developing joints is perturbed upon loss of embryo movement

ABSTRACT Dynamic mechanical loading of synovial joints is necessary for normal joint development, as evidenced in certain clinical conditions, congenital disorders and animal models where dynamic muscle contractions are reduced or absent. Although the importance of mechanical forces on joint development is unequivocal, little is known about the molecular mechanisms involved. Here, using chick and mouse embryos, we observed that molecular changes in expression of multiple genes analyzed in the absence of mechanical stimulation are consistent across species. Our results suggest that abnormal joint development in immobilized embryos involves inappropriate regulation of Wnt and BMP signaling during definition of the emerging joint territories, i.e. reduced β-catenin activation and concomitant upregulation of pSMAD1/5/8 signaling. Moreover, dynamic mechanical loading of the developing knee joint activates Smurf1 expression; our data suggest that Smurf1 insulates the joint region from pSMAD1/5/8 signaling and is essential for maintenance of joint progenitor cell fate. Summary: Dynamic mechanical loading of joints, via muscle contraction, defines an indispensable permissive zone, which is deprived of BMP signaling and is essential for Wnt signaling-induced articular cartilage differentiation.
A Subtle Threat to Urban Populations in Developing Countries: Low Back Pain and its Related Risk Factors

Study Design. A cross-sectional, population-based survey. Objective. The aim of this study was to estimate the prevalence, and biological and psychological correlates of low back pain (LBP) in large, populated urban areas. Summary of Background Data. LBP is a common and costly medical problem all around the world. Currently, there are limited data available on prevalence as well as biological and psychological correlates of LBP in large urban populations in developing countries. Methods. Here, in a cross-sectional, population-based survey, we analyzed data obtained from 22,952 subjects living in Tehran. Results. Chronic, 1-year, and point prevalence of LBP among subjects were 12.2%, 42.1%, and 36.2%, respectively. LBP was more prevalent among older population, women, housewives, and obese people after adjustment for confounding factors using logistic regression models. In addition, persons with a general health questionnaire (GHQ-28) score ≥6 were about 2 times more likely to experience LBP in comparison with others. Both subjects with higher educational levels and those who were never married reported significantly less LBP. Furthermore, we could not find any significant correlation between smoking and physical activity level with LBP. Conclusion. LBP is prevalent among the general population of Tehran. Our findings can help health care providers regarding logical assignment of limited resources, in order to create multidimensional prevention plans according to potentially modifiable associated factors. Level of Evidence: 3
The Influence of London on Labor Markets in Southern England, 1830-1914

Historians have long acknowledged that London, because of its enormous size and rapidly growing demand for labor, acted as a powerful magnet for migrants from throughout southern England. However, while there is a large literature documenting the flow of migrants to London, there have been surprisingly few attempts to determine the consequences of this migration for southern labor markets. This article attempts to redress the imbalance in the literature by examining the influence of London on agricultural labor markets during the nineteenth century. In particular, the article examines the effect of distance from London on wage rates in southern England at various points in time, and the effect of labor market conditions in London on short-run changes in agricultural wage rates.
Influence of Cyclic Loading and Temperature on Integrity of Piezoceramic Patch Transducers

In this study the loading limits, damage behavior and long-term integrity of piezoceramic patch transducers, based on monolithic PZT wafers (PIC 255) were investigated. The presented results involve quasi-static and long-term cyclic testing under tensile as well as compressive mechanical loading of the patches, under varied temperatures. Also long-term cyclic electric activation was investigated. A strain-cycle life-span diagram was established for tensile loading at room temperature (RT), +60 °C, +100 °C and −40 °C. In all cases cracking in the PZT ceramic was found to be the relevant failure mechanism which could be correlated to the observed degradation of the patches’ sensor performance. Preliminary investigations with fracture mechanics methods were carried out on the specimen with fractured PZT wafers. No mechanical damage was found under compressive loading at strain levels of up to −0.6%. Finite element analyses were performed using 3D material modeling with electromechanical coupling behavior, achieving very good predictability of the sensor and actuator performance. Analytical calculations and numerical simulation were used to interpret experimental findings and also allow the transfer of results to various applications.Copyright © 2008 by ASME
Synthetic addiction extends the productive life time of engineered Escherichia coli populations

Significance Bioproduction of chemicals offers a sustainable alternative to petrochemical synthesis routes by using genetically engineered microorganisms to convert waste and simple substrates into higher-value products. However, efficient high-yield production commonly introduces a metabolic burden that selects for subpopulations of nonproducing cells in large fermentations. To postpone such detrimental evolution, we have synthetically addicted production cells to production by carefully linking signals of product presence to expression of nonconditionally essential genes. We addict Escherichia coli cells to their engineered biosynthesis of mevalonic acid by fine-tuned control of essential genes using a product-responsive transcription factor. Over the course of a long-term fermentation equivalent to industrial 200-m3 bioreactors such addicted cells remained productive, unlike the control, in which evolution fully terminated production. Bio-production of chemicals is an important driver of the societal transition toward sustainability. However, fermentations with heavily engineered production organisms can be challenging to scale to industrial volumes. Such fermentations are subject to evolutionary pressures that select for a wide range of genetic variants that disrupt the biosynthetic capacity of the engineered organism. Synthetic product addiction that couples high-yield production of a desired metabolite to expression of nonconditionally essential genes could offer a solution to this problem by selectively favoring cells with biosynthetic capacity in the population without constraining the medium. We constructed such synthetic product addiction by controlling the expression of two nonconditionally essential genes with a mevalonic acid biosensor. The product-addicted production organism retained high-yield mevalonic acid production through 95 generations of cultivation, corresponding to the number of cell generations required for >200-m3 industrial-scale production, at which time the nonaddicted strain completely abolished production. Using deep DNA sequencing, we find that the product-addicted populations do not accumulate genetic variants that compromise biosynthetic capacity, highlighting how synthetic networks can be designed to control genetic population heterogeneity. Such synthetic redesign of evolutionary forces with endogenous processes may be a promising concept for realizing complex cellular designs required for sustainable bio-manufacturing.
FESORIA - An Integrated Tool for Performance and Content Analysis, SLA Evaluation, Management and Smart Presentation for Video-Ondemand Services

This paper presents an integrated tool for performance and content analysis, management, SLA evaluation and smart presentation for video-on-demand services. The improvement in the users’ access lines has originated the appearance of several video-on-demand services. Due to the elevated resources consumption of this kind of services, it is extremely important to obtain a high-quality configuration, which is compulsorily based on the realization of reliable behavioural analyses. In recent years, some specific tools for video-on-demand analysis have appeared. They obtain their data from servers and proxies log files. However, to achieve accurate analyses, further information is necessary, for instance, video metadata or resources consumption statistics. Fesoria is a tool which combines the analysis of log information gathered from the streaming servers and proxies, with other data provided by both the content and the ISP managers. All this information is analyzed in order to generate reports about the service performance and evolution, and the users’ preferences. In addition, the results of these analyses are also employed to establish an intelligent presentation of contents for the users of the service.
Binary Vector based Propositionalization Strategy for Multivalued Relations in Linked Data

Machine learning on linked data is strongly dependent on the selection of high quality data features to achieve good results and build reusable and generalizable models. In this work, we explore the problem of representing multivalued relations in a suitable form for machine learning while keeping the human comprehensibility of the resulting model. Specifically, we propose the use of a binary vector representation and compare it to two state of the art approaches. Our evaluation shows that the binary vector representation achieves mostly higher accuracy in comparison to standard propositionalization techniques. It also achieves comparable accuracy to a recently presented graph embeddings approach, while retaining the human comprehensibility.
The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications

In recent years, investigators have readdressed the complex issues involved in the classification of inflammatory bowel diseases. In 2003, a Working Party of investigators with an interest in the issues involved in disease subclassification was formed with the aim of summarising recent developments in disease classification and establishing an integrated clinical, molecular, and serological classification of inflammatory bowel disease. The results of the Working Party were reported at the 2005 Montreal World Congress of Gastroenterology. Here we highlight the key issues that have emerged from discussions of the Montreal Working Party and the relevance to clinical practice and research activities.
On the Capability of Neural Networks to Approximate the Neyman-Pearson Detector: A Theoretical Study

In this paper, the application of neural networks for approximating the Neyman-Pearson detector is considered. We propose a strategy to identify the training parameters that can be controlled for reducing the effect of approximation errors over the performance of the neural network based detector. The function approximated by a neural network trained using the mean squared-error criterion is deduced, without imposing any restriction on the prior probabilities of the clases and on the desired outputs selected for training, proving that these parameters play an important role in controlling the sensibility of the neural network detector performance to approximation errors. Another important parameter is the signal-to-noise ratio selected for training. The proposed strategy allows to determine its best value, when the statistical properties of the feature vectors are known. As an example, the detection of gaussian signals in gaussian interference is considered.
Development of oral immunomodulatory agents in the management of multiple sclerosis

The emergence of oral disease-modifying therapies in multiple sclerosis (MS) will have a significant impact on the evolving scenario of immunomodulatory treatments in MS where current therapies are all injectable. Reducing relapses in trials translates for individuals with MS into a therapeutic aim of stopping future events. Thus the possible absence of any perceived benefits to the individual together with the long disease course, variable outcome, and a younger age group affected in MS makes side effects the major issue. The use of disease-modifying therapies as a whole needs to be placed in the context of a widening therapeutic indication where the use of these therapies is being justified at an increasingly early stage and in pre-MS syndromes such as clinically isolated and radiologically isolated syndromes where no fixed disability is likely to have accumulated. The five oral therapies discussed (cladribine, fingolimod, laquinimod, BG-12, and teriflunomide) have just completed Phase III studies and some have just been licensed. New oral drugs for MS need to be placed within this evolving marketplace where ease of delivery together with efficacy and side effects needs to be balanced against the known issues but also the known long-term safety of standard injectables.
Hydrogen-induced softening in nanocrystalline Ni investigated by nanoindentation

Abstract The influence of hydrogen on the plastic deformation of nanocrystalline nickel was analysed by recourse to nanoindentation on the uncharged and hydrogen-charged samples. It was revealed that, in nanocrystalline Ni, hydrogen significantly decreases hardness but does not alter the strain rate sensitivity. Through thermal desorption spectroscopy measurement, charged hydrogen was expected to reside in face-centred cubic lattice, grain boundaries (GBs) and vacancies rather than dislocations. The hydrogen-induced softening behaviour is discussed in terms of the possible roles of hydrogen in GB-assisted dislocation flow mechanism.
Geography of intergenerational mobility and child development

Significance Using data from an urban birth cohort study, we show that children from low-income families who grow up in counties that produce high levels of upward mobility, as recently estimated by Chetty and Hendren, exhibit fewer externalizing behaviors by age 3 years and show substantial gains in cognitive test scores between ages 3 and 9 years. These associations are robust to controls for family characteristics, including parental intelligence, impulsivity, and mental health. This paper identifies developmental pathways through which intergenerational mobility of place, measured at the county level, shapes the economic prospects of children from low-income families. Recent research by Chetty and colleagues finds that children’s chances of upward mobility are affected by the communities in which they grow up [Chetty R, Hendren N (2016) Working paper 23002]. However, the developmental pathways through which communities of origin translate into future economic gain are not well understood. In this paper we examine the association between Chetty and Hendren’s county-level measure of intergenerational mobility and children’s cognitive and behavioral development. Focusing on children from low-income families, we find that growing up in a county with high upward mobility is associated with fewer externalizing behavioral problems by age 3 years and with substantial gains in cognitive test scores between ages 3 and 9 years. Growing up in a county with 1 SD better intergenerational mobility accounts for ∼20% of the gap in developmental outcomes between children from low- and high-income families. Collectively, our findings suggest that the developmental processes through which residential contexts promote upward mobility begin early in childhood and involve the enrichment of both cognitive and social-emotional development.
Aphidiinae (Hymenoptera, Braconidae, Aphidiinae) from Slovenia, with descrip-tion of a new Aphidius species

Over the period 2006–2010, 40 species of primary parasitoids belonging to eleven genera were found and reared from 50 species of host aphids, from a total of 106 host plants collected from 62 localities all around Slovenia. Over 230 tritrophic associations have been reviewed, including four associations which are reported for the first time; Ephedrus plagiator/ Staticobium limonii/ Limonium angustifolium, Praon necans/ Staticobium limonii/ Limonium angustifolium, Aphidius sussi/Delphinobium sp. /Aconitum maximum and Ephedrus persicae/Brachyunguis tamaricis/ Tamarix gallica. The parasitoid species from Slovenia have been grouped in seven faunal complexes according to their origin, e.g. 11 species from European deciduous forest, 3 species from Far Eastern deciduous forest, 20 species from Eurasian Steppes, 1 Mediterranean species, 2 species from Holarctic Forest Tundra, 2 species from Boreal Europe, and 1 Nearctic species. Also, a new aphid parasitoid species Aphidius staticobii sp.n. Tomanović and Petrović has been described from the association Staticobium limonii/ Limonium angustifolium.
Shank3‐deficient thalamocortical neurons show HCN channelopathy and alterations in intrinsic electrical properties

Shank3 increases the HCN channel surface expression in heterologous expression systems. Shank3Δ13–16 deficiency causes significant reduction in HCN2 expression and Ih current amplitude in thalamocortical (TC) neurons. Shank3Δ13–16‐ but not Shank3Δ4–9‐deficient TC neurons share changes in basic electrical properties which are comparable to those of HCN2−/− TC neurons. HCN channelopathy may critically mediate events downstream from Shank3 deficiency.
In Vivo Capsular Switch in Streptococcus pneumoniae – Analysis by Whole Genome Sequencing

Two multidrug resistant strains of Streptococcus pneumoniae – SV35-T23 (capsular type 23F) and SV36-T3 (capsular type 3) were recovered from the nasopharynx of two adult patients during an outbreak of pneumococcal disease in a New York hospital in 1996. Both strains belonged to the pandemic lineage PMEN1 but they differed strikingly in virulence when tested in the mouse model of IP infection: as few as 1000 CFU of SV36 killed all mice within 24 hours after inoculation while SV35-T23 was avirulent. Whole genome sequencing (WGS) of the two isolates was performed (i) to test if these two isolates belonging to the same clonal type and recovered from an identical epidemiological scenario only differed in their capsular genes? and (ii) to test if the vast difference in virulence between the strains was mostly – or exclusively – due to the type III capsule. WGS demonstrated extensive differences between the two isolates including over 2500 single nucleotide polymorphisms in core genes and also differences in 36 genetic determinants: 25 of which were unique to SV35-T23 and 11 unique to strain SV36-T3. Nineteen of these differences were capsular genes and 9 bacteriocin genes. Using genetic transformation in the laboratory, the capsular region of SV35-T23 was replaced by the type 3 capsular genes from SV36-T3 to generate the recombinant SV35-T3* which was as virulent as the parental strain SV36-T3* in the murine model and the type 3 capsule was the major virulence factor in the chinchilla model as well. On the other hand, a careful comparison of strains SV36-T3 and the laboratory constructed SV35-T3* in the chinchilla model suggested that some additional determinants present in SV36 but not in the laboratory recombinant may also contribute to the progression of middle ear disease. The nature of this determinants remains to be identified.
Determination of Membrane Protein Distribution on the Nuclear Envelope by Single‐Point Single‐Molecule FRAP

Nuclear envelope transmembrane proteins (NETs) are synthesized on the endoplasmic reticulum and then transported from the outer nuclear membrane (ONM) to the inner nuclear membrane (INM) in eukaryotic cells. The abnormal distribution of NETs has been associated with many human diseases. However, quantitative determination of the spatial distribution and translocation dynamics of NETs on the ONM and INM is still very limited in currently existing approaches. Here we demonstrate a single‐point single‐molecule fluorescence recovery after photobleaching (FRAP) microscopy technique that enables quick determination of distribution and translocation rates for NETs in vivo. © 2017 by John Wiley & Sons, Inc.
Relevance of Negative Links in Graph Partitioning: A Case Study Using Votes from the European Parliament

In this paper, we want to study the informative value of negative links in signed complex networks. For this purpose, we extract and analyze a collection of signed networks representing voting sessions of the European Parliament (EP). We first process some data collected by the Vote Watch Europe Website for the whole 7th term (2009-2014), by considering voting similarities between Members of the EP to define weighted signed links. We then apply a selection of community detection algorithms, designed to process only positive links, to these data. We also apply Parallel Iterative Local Search (Parallel ILS), an algorithm recently proposed to identify balanced partitions in signed networks. Our results show that, contrary to the conclusions of a previous study focusing on other data, the partitions detected by ignoring or considering the negative links are indeed remarkably different for these networks. The relevance of negative links for graph partitioning therefore is an open question which should be further explored.
Using Quantitative Spectrometry to Understand the Influence of Genetics and Nutritional Perturbations On the Virulence Potential of Staphylococcus aureus*

Staphylococcus aureus (Sa) is the leading cause of a variety of bacterial infections ranging from superficial skin infections to invasive and life threatening diseases such as septic bacteremia, necrotizing pneumonia, and endocarditis. The success of Sa as a human pathogen is contributed to its ability to adapt to different environments by changing expression, production, or secretion of virulence factors. Although Sa immune evasion is well-studied, the regulation of virulence factors under different nutrient and growth conditions is still not well understood. Here, we used label-free quantitative mass spectrometry to quantify and compare the Sa exoproteins (i.e. exoproteomes) of master regulator mutants or established reference strains. Different environmental conditions were addressed by growing the bacteria in rich or minimal media at different phases of growth. We observed clear differences in the composition of the exoproteomes depending on the genetic background or growth conditions. The relative abundance of cytotoxins determined in our study correlated well with differences in cytotoxicity measured by lysis of human neutrophils. Our findings demonstrate that label-free quantitative mass spectrometry is a versatile tool for predicting the virulence of bacterial strains and highlights the importance of the experimental design for in vitro studies. Furthermore, the results indicate that label-free proteomics can be used to cluster isolates into groups with similar virulence properties, highlighting the power of label-free quantitative mass spectrometry to distinguish Sa strains.