Miracle-dz/UniFAR-FTUs huggingface dataset:
A unique epigenetic signature is associated with active DNA replication loci in human embryonic stem cells

The cellular epigenetic landscape changes as pluripotent stem cells differentiate to somatic cells or when differentiated cells transform to a cancerous state. These epigenetic changes are commonly correlated with differences in gene expression. Whether active DNA replication is also associated with distinct chromatin environments in these developmentally and phenotypically diverse cell types has not been known. Here, we used BrdU-seq to map active DNA replication loci in human embryonic stem cells (hESCs), normal primary fibroblasts and a cancer cell line, and correlated these maps to the epigenome. In all cell lines, the majority of BrdU peaks were enriched in euchromatin and at DNA repetitive elements, especially at microsatellite repeats, and coincided with previously determined replication origins. The most prominent BrdU peaks were shared between all cells but a sizable fraction of the peaks were specific to each cell type and associated with cell type-specific genes. Surprisingly, the BrdU peaks that were common to all cell lines were associated with H3K18ac, H3K56ac, and H4K20me1 histone marks only in hESCs but not in normal fibroblasts or cancer cells. Depletion of the histone acetyltransferases for H3K18 and H3K56 dramatically decreased the number and intensity of BrdU peaks in hESCs. Our data reveal a unique epigenetic signature that distinguishes active replication loci in hESCs from normal somatic or malignant cells.
HTTP Strict Transport Security (HSTS)

This specification defines a mechanism enabling web sites to declare themselves accessible only via secure connections and/or for users to be able to direct their user agent(s) to interact with given sites only over secure connections. This overall policy is referred to as HTTP Strict Transport Security (HSTS). The policy is declared by web sites via the Strict-Transport-Security HTTP response header field and/or by other means, such as user agent configuration, for example. [STANDARDS-TRACK]
Dynamic causal modelling for schizophrenia

Schizophrenia is a complex psychiatric disorder which leads to local abnormalities in brain activity. Functional Magnetic Resonance Imaging (fMRI) technology enables medical doctors to observe brain activity patterns that represent the execution of subject tasks, both physical and mental. In general, each subject exhibits his own activation pattern for a given task, whose intensity is affected by the physiology of the subject's brain, the usage of medications, and the parameters of the scanner used for image acquisition. Since it is possible to co-register the resulting activation map to a standard brain, all activation patterns from the different individuals can be analyzed in terms of consistency on the brain sections or brain coordinates where the activation is observed. The dynamic Causal Model using Bayesian networks (DBNs) extracts causal relationships from functional magnetic resonance imaging (fMRI) data applying HITON-PC, a local causal algorithm. Based on these relationships, a dynamic causal model is to be build that is used to classify patient data as belonging to healthy or ill subjects. Causal Explorer is a Matlab library of computational causal discovery and variable selection algorithms.
Learning and Inferring Representations of Data in Neural Networks

Finding useful representations of data in order to facilitate scientific knowledge generation is a ubiquitous concept across disciplines. Until the development of machine learning and statistical methods with hidden or latent representations, useful representations of data were generated “by hand” through scientific modeling or simple measurement observations. Scientific models often make explicit the underlying structure of a system which generates the data we observe and measure. To test a model, inferences must be made about the free parameters and the distributions of latent or unmeasured variables in the model conditioned on the data collected. At this time, many scientific disciplines such as astronomy, particle physics, wildlife conservation, and neuroscience have been moving towards collecting datasets that are large and complex enough so that no human will ever look at and analyze all measurements by hand. Datasets of this scale present an interesting scientific opportunity: to be able to derive insight into the structure of natural systems by creating models which can adapt themselves to the latent structure of large amounts of data, often called data-driven hypothesis testing. The three topics of this work fall under this umbrella, but are largely independent research directions. First, we show how deep learning can be used to infer representations of neural data which can be used to find the limits of information content in sparsely sampled neural activity and applied to improving the performance of brain-computer interfaces. Second, we derive a circuit model for a network neurons which implements approximate inference in a probabilistic model given the biological constraint of neuron-local computations. Finally, we provide a theoretical and empirical analysis of a family of methods for learning linear representations which have low coherence (cosine-similarity) and show that linear methods have limited applicability as compared to nonlinear, recurrent models which solve the same problem. Together, these results provide insight into how scientists and the brain can learn useful representations of data in deep and single layer networks.
Relationship between cardiac function and resting cerebral blood flow: MRI measurements in healthy elderly subjects

Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF and cardiac output were measured in 31 healthy subjects 50–75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43·6 ml per 100 g min−1, 5·5 l min−1 and 2·7 l min−1 m−2, respectively, in males, and 53·4 ml per 100 g min−1, 4·3 l min−1 and 2·4 l min−1 m−2, respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r2 = 0·22, P = 0·008) and furthermore lower in males than in females (8·6% versus 12·5%, P = 0·003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed a gender‐related inverse association of increased low‐to‐high‐frequency power ratio with CBF and fractional brain flow. The findings do not support a direct effect of cardiac function on CBF, but demonstrates gender‐related differences in cardiac output distribution. We propose fractional brain flow as a novel index that may be a useful marker of adequate brain perfusion in the context of ageing as well as cardiovascular disease.
Information Flow on Digital Social Networks during a Cultural Event: Methodology and Analysis of the "European Night of Museums 2016" on Twitter

In this paper, we first present a representation of message flows and their contents on Twitter, then an instrumented methodology to describe and analyze these flows and their distribution among the various stakeholders. The aim is to explore the engagement and interactions between different types of stakeholders. We apply our methodology and tools to the 12th edition of the cultural event "European Night of Museums" (NDM16).
Cadmium impairment of reproduction in the female wall lizard Podarcis sicula

The exposure to environmental toxicants such cadmium (Cd) is an important research area in wildlife protection. In this study, the effect of Cd oral administration on the ovarian structure and function and on reproductive performance of the Italian wall lizard Podarcis sicula was studied. In vivo, adult female lizards were randomly assigned to three groups. Cd was given with food in single dose and in multiple doses 3 days/week for 4 weeks at dose of 1.0 μg/g body weight. Following euthanasia, the ovaries were removed and analyzed for morpho‐functional changes. Results demonstrated that Cd increases prefollicular germ cells number; the evaluation of the number of follicles detects significantly higher number of atretic growing follicles, whereas primary follicles remain unchanged with respect to controls. After Cd treatments, follicles are deformed by the presence of large protrusions and a general dysregulation in the follicle organization is observed. The zona pellucida is also affected. Cd causes alteration in sugar metabolism and in metallothionein gene expression. Finally, Cd administration significantly reduces clutch size and dramatically increases embryo mortality. In conclusion, data here described show that Cd induces morpho‐functional alterations in lizard follicles and indicates that these are responsible for a significant impairment of oogenesis. The effects of the dose are time independent, persisting essentially unchanged regardless of single or multiple administration, so it can be concluded that even occasional, sublethal Cd contamination may significantly impair reproductive performance in these animals. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 553–562, 2013.
Influence of peptide dipoles and hydrogen bonds on reactive cysteine pKa values in fission yeast DJ‐1

Cysteine residues with depressed pKa values are critical for the functions of many proteins. Several types of interactions can stabilize cysteine thiolate anions, including hydrogen bonds between thiol(ate)s and nearby residues as well as electrostatic interactions involving charged residues or dipoles. Dipolar stabilization of thiolates by peptide groups has been suggested to play a particularly important role near the N‐termini of α‐helices. Using a combination of X‐ray crystallography, site‐directed mutagenesis and spectroscopic methods, we show that the reactive cysteine residue (Cys111) in Schizosaccharomyces pombe DJ‐1 experiences a 0.6 unit depression of its thiol pKa as a consequence of a hydrogen bond donated by a threonine side chain (Thr114) to a nearby peptide carbonyl oxygen at the N‐terminus of an α‐helix. This extended hydrogen bonded interaction is consistent with a sum of dipoles model whereby the distal hydrogen bond polarizes and strengthens the direct hydrogen bond between the proximal amide hydrogen and the cysteine thiol(ate). Therefore, our results suggest that the local dipolar enhancement of hydrogen bonds can appreciably stabilize cysteine thiolate formation. However, the substitution of a valine residue with a proline at the i + 3 position has only a minor effect (0.3 units) on the pKa of Cys111. As proline has a reduced peptide dipole moment, this small effect suggests that a more extended helix macrodipolar effect does not play a major role in this system.
Growth of early or midterm human foetal skin in a burn model: establishment of the model, morphological and histological observations

Objective: To construct a burn model of early and midterm human Foetal Skin (hFS) in vitro, to observe its morphological and histological changes after transplantation, and to examine the expression of Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinases (TIMPs), and further to analyse their roles in foetal wound healing preliminarily. Methods: hFS harvested from aborted foetuses (gestational age 14-24 weeks) was transplanted into the backs of nude mice. Four weeks later, a burn wound was made in the transplanted foetal skin with a thermostatic electrical scald apparatus. To examine the role of exogenous mature immune cells, human Peripheral Blood Mononuclear Cells (hPBMCs) were injected into the subcutaneous layer of transplanted hFS. The histological characteristics and the expression of MMP-2, MMP-7, MMP-9, and TIMP-1 were examined during the wound-healing process above. Results: The transplanted foetal skin survived on the backs of mice, the burn wounds healed rapidly and without scarring, and skin appendages regenerated after the epidermis were repaired. Injection of hPBMCs prolonged the burn wound-healing process and caused obvious scarring. MMP-2 expression was observed in the surviving grafts, but MMP-7 expression was not observed throughout the normal growth process after transplantation. MMP-7 expression was observed around the burn wound, but MMP-2 expression was observed only in surviving follicles. MMP-9 expression was observed in the cytoplasm of deep epithelial cells of skin appendages. TIMP-1 expression level was slightly lower than that of MMP-9, although its pattern of expression was similar to that of MMP-9. Injection of exogenous mature immune cells (hPBMCs) into the burn injury changed the patterns of MMP-9 and TIMP-1 expression. Conclusion: Our method for constructing an early or midterm hFS burn model is simple and reliable. HFS maintains the ability for scarless wound healing and regeneration when transplanted into nude mice. This new animal model may be suitable for investigating the mechanisms responsible for hFS wound healing. Injection of hPBMCs prolonged burn wound healing and caused the formation of scars in the wound. MMPs and TIMPs expression might be important factors for scarless wound healing.
A numerical model for solving two dimensional Poisson-Schrödinger equation in depletion all around operation of the SOI four gate transistor

A numerical model is developed for solving two dimensional Poisson-Schrödinger equation in depletion-all-around (DAA) operation of n-channel four gate transistor (G4FET) by finite element method using COMSOL with MATLAB. The results from this model can be used to calculate ballistic drain current by mode-space approach. Potential distribution, conduction band profile, eigen energy profile and wave function distribution are observed.
A Novel Six-Rhodopsin System in a Single Archaeon

ABSTRACT Microbial rhodopsins, a diverse group of photoactive proteins found in Archaea, Bacteria, and Eukarya, function in photosensing and photoenergy harvesting and may have been present in the resource-limited early global environment. Four different physiological functions have been identified and characterized for nearly 5,000 retinal-binding photoreceptors, these being ion transporters that transport proton or chloride and sensory rhodopsins that mediate light-attractant and/or -repellent responses. The greatest number of rhodopsins previously observed in a single archaeon had been four. Here, we report a newly discovered six-rhodopsin system in a single archaeon, Haloarcula marismortui, which shows a more diverse absorbance spectral distribution than any previously known rhodopsin system, and, for the first time, two light-driven proton transporters that respond to the same wavelength. All six rhodopsins, the greatest number ever identified in a single archaeon, were first shown to be expressed in H. marismortui, and these were then overexpressed in Escherichia coli. The proteins were purified for absorption spectra and photocycle determination, followed by measurement of ion transportation and phototaxis. The results clearly indicate the existence of a proton transporter system with two isochromatic rhodopsins and a new type of sensory rhodopsin-like transducer in H. marismortui.
A Hybrid Genetic Algorithm for the Airline Crew Assignment Problem

A typical problem related to airline crew management consists of optimally assigning the required crew members to flights for a period of time, while complying with labor regulations, safety rules and policies of the airline. This problem, called the Crew Assignment Problem (CAP), is a combinatorial optimization problem. Hence, a Hybrid Genetic Algorithm (HGA) associated with a constructive heuristic and a local search was developed. The HGA was tested and applied to solve instances related to a Brazilian airline.
Examining the role of red background in magnocellular contribution to face perception

This study examines the role of the magnocellular system in the early stages of face perception, in particular sex categorization. Utilizing the specific property of magnocellular suppression in red light, we investigated visually guided reaching to low and high spatial frequency hybrid faces against red and grey backgrounds. The arm movement curvature measure shows that reduced response of the magnocellular pathway interferes with the low spatial frequency component of face perception. This finding provides behavioral evidence for magnocellular contribution to non-emotional aspect of face perception.
Modeling of $\hbox{As}_{2}\hbox{S}_{3}$ Raman Fiber Lasers Operating in the Mid-Infrared

A numerical study of As2S3 Raman fiber lasers is carried out to show their potential for the entire coverage of the 3-4-μm spectral band. Experimental results are first obtained from such a laser operated under controlled conditions in order to set the fiber parameters (i.e., gain and attenuation coefficients) to be used in the numerical model. An exhaustive numerical analysis is then performed to establish the conditions for optimum lasing performances over the entire 3-4-μm spectral band.
Dealing with missing values for effective prediction of NPC recurrence

This paper aims to investigate missing data techniques for effective prediction of nasopharyngeal carcinoma (NPC) recurrence. The techniques include listwise deletion, imputations by mean, k-nearest neighbor, and expectation maximization. The completed data are used to predict the presence or absence of NPC recurrence in each year by means of logistic regression, multilayer perceptron with backpropagation training, and naive bayes. Five year predictions are carried out. Validity of each predictive model is assured by 10-fold cross validation. Their results are compared in order to determine proper missing data treatment and the most efficient prediction technique. The results showed that EM imputation was superior to the other missing data techniques because it can be efficiently applied to all predictive models. The multilayer perceptron with backpropagation training gave the highest prediction performance and it was the most robust to the data completed by different missing data techniques.
Discovery of a novel anti-cancer agent targeting both topoisomerase I and II in hepatocellular carcinoma Hep 3B cells in vitro and in vivo: Cinnamomum verum component 2-methoxycinnamaldehyde

Abstract Cinnamomum verum has been used as a traditional Chinese herbal medicine. We evaluated the anticancer effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the bark of the plant, in hepatocellular carcinoma Hep 3B cells. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by an up-regulation of pro-apoptotic bax and bak genes and down-regulation of anti-apoptotic bcl-2 and bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase 3 and 9, increase in the DNA content in sub G1, and morphological characteristics of apoptosis. 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartments (VAC), suppressions of nuclear transcription factors NF-κB, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and both topoisomerase I and II activities in a dose-dependent manner. Further study reveals the growth-inhibitory effect of 2-MCA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of 2-MCA against Hep 3B cells is accompanied by downregulations of NF-κB binding activity, inflammatory responses involving COX-2 and PGE2, and proliferative control involving apoptosis, both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and VAC. Our data suggest that 2-MCA could be a potential agent for anticancer therapy.
Accelerating Time-Dependent Multi-Criteria Timetable Information is Harder Than Expected

Speeding up multi-criteria search in real timetable information systems remains a challenge in spite of impressive progress achieved in recent years for related problems in road networks. Our goal is to perform multi-criteria range queries, that is, to find all Pareto-optimal connections with respect to travel time and number of transfers within a given start time interval. This problem can be modeled as a path search problem in a time- and event-dependent graph. In this paper, we investigate two key speed-up techniques for a multi-criteria variant of \textsc{Dijkstra}'s algorithm --- arc flags and contraction --- which seem to be strong candidates for railway networks, too. We describe in detail how these two techniques have to be adapted for a multi-criteria scenario and explain why we can expect only marginal speed-ups (compared to observations in road networks) from a direct implementation. Based on these insights we extend traditional arc-flags to \emph{time-period flags} and introduce \emph{route contraction} as a substitute for node contraction. A computational study on real queries demonstrates that these techniques combined with goal-directed search lead to a speed-up of factor 13.08 over the baseline variant for range queries for a full day.
Single Nucleotide Polymorphism Mapping Using Genome-Wide Unique Sequences

As more and more genomic DNAs are sequenced to characterize human genetic variations, the demand for a very fast and accurate method to genomically position these DNA sequences is high. We have developed a new mapping method that does not require sequence alignment. In this method, we first identified DNA fragments of 15 bp in length that are unique in the human genome and then used them to position single nucleotide polymorphism (SNP) sequences. By use of four desktop personal computers with AMD K7 (1 GHz) processors, our new method mapped more than 1.6 million SNP sequences in 20 hr and achieved a very good agreement with mapping results from alignment-based methods.
Analysis of the genomic response of human prostate cancer cells to histone deacetylase inhibitors

Histone deacetylases (HDACs) have emerged as important targets for cancer treatment. HDAC-inhibitors (HDACis) are well tolerated in patients and have been approved for the treatment of patients with cutaneous T-cell lymphoma (CTCL). To improve the clinical benefit of HDACis in solid tumors, combination strategies with HDACis could be employed. In this study, we applied Analysis of Functional Annotation (AFA) to provide a comprehensive list of genes and pathways affected upon HDACi-treatment in prostate cancer cells. This approach provides an unbiased and objective approach to high throughput data mining. By performing AFA on gene expression data from prostate cancer cell lines DU-145 (an HDACi-sensitive cell line) and PC3 (a relatively HDACi-resistant cell line) treated with HDACis valproic acid or vorinostat, we identified biological processes that are affected by HDACis and are therefore potential treatment targets for combination therapy. Our analysis revealed that HDAC-inhibition resulted among others in upregulation of major histocompatibility complex (MHC) genes and deregulation of the mitotic spindle checkpoint by downregulation of genes involved in mitosis. These findings were confirmed by AFA on publicly available data sets from HDACi-treated prostate cancer cells. In total, we analyzed 375 microarrays with HDACi treated and non-treated (control) prostate cancer cells. All results from this extensive analysis are provided as an online research source (available at the journal’s website and at http://luigimarchionni.org/HDACIs.html). By publishing this data, we aim to enhance our understanding of the cellular changes after HDAC-inhibition, and to identify novel potential combination strategies with HDACis for the treatment of prostate cancer patients.