Miracle-dz/UniFAR-FTUs huggingface dataset:
A simple coarse-grained model for self-assembling silk-like protein fibers.

Collagen-silk-collagen triblock polypeptides can self-assemble at low pH into nanometer thin fibers with a length in the order of micrometers. Previously we predicted, via all-atom simulations, the structure of the folded silk domain to be a beta-roll. In this work we develop a simple coarse-grained model of the silk domain to enable a numerical study of the fiber's properties and formation on a larger length and time scale. As an initial coarse-grained model for the fiber forming protein we chose the model of Brown et al., Proc. Natl. Acad Sci. U.S.A. , 2003, 100, 10712-10717. We adapted this model, and optimized its parameters to reproduce the all-atom molecular dynamics simulation structural data. The unknown strength of the attraction between the beads representing the residues is optimized by computing the Potential of Mean Force for unfolding a strand of the beta-roll, using non-equilibrium steered MD simulations in combination with the Jarzynski relation. Using these optimized parameters we observed spontaneous folding of a short peptide. The coarse-grained beta-roll, as well as a much larger stack (a fiber) of beta-rolls, were found to be stable. Moreover, the predicted fiber persistence length is in agreement with experiment. The efficacy of the mapping of a coarse-grained system onto an all-atom simulation is discussed. The approach opens the way for large-scale simulations of fibers, based on molecular structure, and allows investigation of their nucleation, growth, cross-linking mechanism, network dynamics, and rheology.
Interferon-Induced ISG15 Conjugation Inhibits Influenza A Virus Gene Expression and Replication in Human Cells

ABSTRACT The ubiquitin-like ISG15 protein, as well as its conjugating enzymes, is induced by type I interferons (IFNs). Experiments using ISG15 knockout (ISG15−/−) mice established that ISG15 and/or its conjugation inhibits the replication of influenza A virus. However, in contrast to the virus inhibition results for mice, the rates of virus replication in ISG15+/+ and ISG15−/− mouse embryo fibroblasts in tissue culture were similar. Here we focus on human tissue culture cells and on the effect of ISG15 and/or its conjugation on influenza A virus gene expression and replication in such cells. We demonstrate that IFN-induced antiviral activity against influenza A virus in human cells is significantly alleviated by inhibiting ISG15 conjugation using small interfering RNAs directed against ISG15-conjugating enzymes. IFN-induced antiviral activity against influenza A virus protein synthesis was reduced 5- to 20-fold by suppressing ISG15 conjugation. The amounts of the viral proteins that were restored by these siRNA treatments were approximately 40 to 50% of the amounts produced in cells that were not pretreated with IFN. Further, we show that ISG15 conjugation inhibits influenza A virus replication 10- to 20-fold at early times after infection in human cells. These results show that ISG15 conjugation plays a substantial role in the antiviral state induced by IFN in human cells. In contrast, we show that in mouse embryo fibroblasts ISG15 conjugation not only does not affect influenza A virus replication but also does not contribute to the IFN-induced antiviral activity against influenza A virus gene expression.
Epstein–Barr virus infection and plasma transforming growth factor-β1 levels in head and neck cancers

Conclusions. In addition to the correlation of transforming growth factor (TGF)-β1 levels to the radiation toxicity, both Epstein–Barr virus (EBV) infection and postoperative status play roles in the change in plasma TGF-β1 levels in patients with head and neck cancers. Objectives. To assess the parameters involved in the change in plasma TGF-β1 level during concurrent chemoradiotherapy (CCRT). Patients and methods. Blood samples (n=307) before, during, and after treatment were obtained from 39 patients with head and neck cancers treated with definitive or adjuvant CCRT. In situ hybridization (ISH) was used to identify EBV-encoded RNA (EBER) in tissues from the primary tumor or metastatic lymph nodes. Plasma TGF-β1 level, white blood cell (WBC), and platelet count were assayed immediately before the first fraction of radiotherapy (RT), once a week during RT, and at the end of the RT course. The grades of mucositis and dermatitis were recorded weekly during CCRT. Results. Pretreatment TGF-β1 level and radiation toxicity were found to be significantly correlated with the increase of the plasma TGF-β1 level during CCRT (p<0.05), but correlation of platelet count was only found in patients whose tumors were EBV-positive (p=0.0042), and WBC count in those treated with postoperative adjuvant CCRT (p=0.004).
Determination of the fourth and fifth limiting amino acids in broilers fed on diets containing maize, soybean meal and poultry by-product meal from 28 to 42 d of age

1. Valine (Val) is considered the 4th limiting amino acid for broilers fed on diets containing ingredients from vegetable origin. However, Val and Isoleucine (Ile) may be co-limiting for broilers fed on diets containing animal protein meals. An experiment was conducted to examine growth responses and meat yield of broilers provided diets varying in digestible Val (dVal) and digestible Ile (dIle) concentrations from 28 to 42 d of age. 2. Eight experimental diets varying in dVal (dVal to dLys ratios from 0·66 to 0·76) and dIle (dIle to dLys ratios from 0·57 to 0·67) were studied; digestible Lysine (Lys) was formulated to 9·9 g/kg in all diets. 3. Broilers fed on a negative control (NC) diet supplemented with crystalline Val (L-Val) and crystalline Ile (L-Ile), dVal to dLys = 0·76 and dIle to dLys = 0·67, grew faster and had higher breast meat yield than birds fed on NC + L-Ile (dVal to dLys = 0·66 and dIle to dLys = 0·67), NC + L-Val (dVal to dLys = 0·76 and dIle to dLys = 0·57), and NC + reduced L-Val and L-Ile (dVal to dLys = 0·71 and dIle to dLys = 0·62). 4. Feeding broilers on the NC + L-Val and L-Ile (dVal to dLys = 0·76 and dIle to dLys = 0·67) diets gave similar BW gain, carcase weight and yield and total breast meat weight and yield to birds fed on the positive control-fed broilers with no added L-Val and L-Ile (dVal to dLys = 0·76 and dIle to dLys = 0·67). 5. These results indicate that Val and Ile are co-limiting in diets containing poultry by-product meal.
Towards Trustworthy Online Voting: Distributed Aggregation of Confidential Data. (Confiance dans le vote en ligne : Agrégation distribuée de données confidentielles)

Aggregation of values that need to be kept confidential while guaranteeing the robustness of the process and the correctness of the result is necessary for an increasing number of applications. Various kinds of surveys, such as medical ones, opinion polls, referendums, elections, as well as new services of the Internet of Things, such as home automation, require the aggregation of confidential data. In general, the confidentiality is ensured on the basis of trusted third parties or promises of cryptography, whose capacities cannot be assessed without expert knowledge. The ambition of this thesis is to reduce the need for trust in both authorities and technology and explore methods for large-scale data aggregations, that ensure a high degree of confidentiality and rely neither on trusted third parties nor solely on cryptography. Inspired by BitTorrent and Bitcoin, P2P protocols are considered. The first contribution of this thesis is the extension of the distributed aggregation protocol BitBallot with the objective to cover aggregations in P2P networks comprising adversarial peers with fail-stop or Byzantine behaviour. The introduced changes allow eventually to maintain an accurate result in presence of an adversarial minority. The encountered scalability limitations lead to the second contribution with the objective to support large-scale aggregations. Inspired by both BitBallot and BitTorrent, a novel distributed protocol called ADVOKAT is proposed. In both protocols, peers are assigned to leaf nodes of a tree overlay network which determines the computation of intermediate aggregates and restricts the exchange of data. The partition of data and computation among a network of equipotent peers limits the potential for data breaches and reduces the need for trust in authorities. The protocols provide a middleware layer whose flexibility is demonstrated by voting and lottery applications.
Multiscale brain modelling

A central difficulty of brain modelling is to span the range of spatio-temporal scales from synapses to the whole brain. This paper overviews results from a recent model of the generation of brain electrical activity that incorporates both basic microscopic neurophysiology and large-scale brain anatomy to predict brain electrical activity at scales from a few tenths of a millimetre to the whole brain. This model incorporates synaptic and dendritic dynamics, nonlinearity of the firing response, axonal propagation and corticocortical and corticothalamic pathways. Its relatively few parameters measure quantities such as synaptic strengths, corticothalamic delays, synaptic and dendritic time constants, and axonal ranges, and are all constrained by independent physiological measurements. It reproduces quantitative forms of electroencephalograms seen in various states of arousal, evoked response potentials, coherence functions, seizure dynamics and other phenomena. Fitting model predictions to experimental data enables underlying physiological parameters to be inferred, giving a new non-invasive window into brain function that complements slower, but finer-resolution, techniques such as fMRI. Because the parameters measure physiological quantities relating to multiple scales, and probe deep structures such as the thalamus, this will permit the testing of a range of hypotheses about vigilance, cognition, drug action and brain function. In addition, referencing to a standardized database of subjects adds strength and specificity to characterizations obtained.
Tobacco abstinence symptom suppression: the role played by the smoking-related stimuli that are delivered by denicotinized cigarettes.

AIMS Cigarette smoking causes cancer and disease, yet people find quitting difficult due to aversive symptoms that accompany tobacco abstinence. Understanding how to suppress these symptoms is critical in developing effective smoking cessation treatments. Pharmacologically, pure nicotine suppresses tobacco abstinence symptoms partially, and non-nicotine, smoking-related stimuli suppress these abstinence symptoms fully, at least for 24 hours. The current study was designed to clarify the impact of smoking-related stimuli on tobacco withdrawal, and to explore the duration of their ability to suppress withdrawal in smokers. DESIGN Three double-blind, within-subjects, Latin square-ordered, 5-day conditions in which participants smoked nicotinized, denicotinized or no cigarettes. SETTING Out-patient laboratory at Virginia Commonwealth University. PARTICIPANTS Thirteen women and 19 men. MEASUREMENTS Subjective, physiological and performance measures were collected daily and compliance with study conditions was verified objectively. FINDINGS Smoking-related stimuli are sufficient for suppressing some symptoms of tobacco abstinence over a 5-day period [i.e. Questionnaire of Smoking Urges (QSU) factor 1, 'Desire for sweets', 'Hunger' and 'Urges to smoke'], while in this study a combination of nicotine and smoking-related stimuli suppressed other symptoms (i.e. 'Difficulty concentrating', 'Increased eating', 'Restlessness' and 'Impatient'). CONCLUSIONS These results indicate that, while some tobacco abstinence symptoms may be suppressed with nicotine, suppressing others may also require strategies that address the absence of smoking-related stimuli.
Continuous-time algorithm for distributed nonsmooth optimization via decomposition design

This paper is concerned with a class of distributed nonsmooth convex constrained optimization problems with set constraints. The objective function is a sum of local convex functions, which are not necessarily differentiable. A new distributed continuous-time gradient-based algorithm using the decomposition design is explicitly constructed to solve the distributed optimization problem. Rigorous proofs using nonsmooth convex optimization theory and stability theory of differential inclusions are presented. A numerical simulation is conducted to show the efficacy of the proposed algorithm.
Unexpected functions of lncRNAs in gene regulation

Long non-coding RNAs (lncRNAs) are a group of molecules that function in gene regulation in yeast, plants and mammals. The precise mechanisms of action for lncRNAs, however, remain largely unclear. The GAL gene cluster has been used as a model system to study the function of these molecules in Saccharomyces cerevisiae, with a historical focus on lncRNA-dependent repression. Strikingly, in characterizing the role of the RNA helicase Dbp2, we discovered that the GAL lncRNAs could also promote transcriptional activation of the targeted GAL protein-coding genes. Interestingly, these lncRNAs help determine how quickly the GAL genes can be induced in response to galactose, without altering final steady-state transcript levels. This unexpected finding suggests that one role for lncRNAs is to promote the timing of gene expression. Herein, we discuss our discoveries in the context of current models of lncRNA functions in eukaryotes, with a key emphasis on future challenges for genomic research.
Pharmacological and non-pharmacological treatment preferences of healthcare professionals and proxies for challenging behaviors in patients with dementia

ABSTRACT Background: Prescribing antipsychotics to patients with neuropsychiatric symptoms is a matter of concern. Physicians have to make treatment decisions for patients with dementia together with proxies and/or nurses. However, it is unknown whether physicians, nurses, and proxies’ treatment preferences are aligned; hence this study. Methods: Sixteen treatment attributes were selected to elicit the preferences of physicians and nurses. Ten of these attributes were used for the proxies. Preferences were estimated using a case-1 Best-Worst-Scaling design; respondents are asked to select the best and worst attribute on being presented with a hypothetical patient with dementia demonstrating neuropsychiatric symptoms. The treatments offered are: antipsychotic treatment or non-pharmaceutical regimens. Results: The questionnaire was filled in by 41 physicians, 81 nurses, and 59 proxies. The non-pharmacological treatment option was chosen by 52% of the proxies and 71% of the physicians and nurses. The respondents who chose antipsychotics rated the aspects “fastest result” and “most effective” as important. Physicians ranked “experience with antipsychotics” as an important aspect for prescribing antipsychotics. Only the proxies rated the aspect “having a low negative effect on the patient” as important. The nurses and elderly care physicians who chose the non-pharmaceutical treatment ranked “appropriateness” and “of little burden to the patient” as important aspects. Conclusions: While doctors and nurses prefer non-pharmacological interventions, proxies indicated a preference for pharmacological treatment because of the immediate effect. However, physicians follow treatment guidelines and nurses and proxies rely on the physician's recommendations. We suggest physicians should be sensitive to these differences.
A Review of Image Quality Assessment with application to Computational Photography

Image quality assessment has been of major importance for several domains of the industry of image as for instance restoration or communication and coding. New application fieds are opening today with the increase of embedded power in the camera and the emergence of computational photography: automatic tunning, image selection, image fusion, image data-base building, etc. We review the literature of image quality evaluation. We pay attention to the very dfferent undelying hypotheses and results of the existing methods to approach the problem. We explain why they dffer and for which applications they may be beneficial. We also underline their limits, especialy for a possible use in the novel domain of computational photography. Being developed to address dfferent objectives, they propose answers on dfferent aspects, which make them sometimes complementary. However, they all remain limited in their capability to challenge the human expert, the said or unsaid ultimate goal. We consider the methods which are based on retrieving the parameters of a signal, mostly in spectral analysis; then we explore the more global methods to qualify the image quality in terms of noticeable defects or degradation as popular in the compression domain; in a third field the image acquisition process is considered as a channel between the source and the receiver, allowing to use the tools of the information theory and to qualify the system in terms of entropy and information capacity. However, these dfferent approaches hardly attack the most dffcult part of the task which is tomeasure the quality of the photography in terms of aesthetic properties. To help in addressing this problem, in between Phylosophy, Biology and Psychology, we propose a brief review of the litterature which addresses the problematic of qualifying Beauty, present the attempts to adapt these concepts to visual patterns and initiate a re exion on what could be done in the field of photography.
Down‐regulation of regulatory proteins for differentiation and proliferation in murine fetal hypoplastic lungs: Altered mesenchymal‐epithelial interactions *

We compared proliferation (growth) and differentiation (development) related proteins in normal and hypoplastic fetal murine lungs. The hypoplastic lungs were created in CD‐1 fetal mice by nitrofen exposure (25 mg per pregnant mouse given intragastrically on gestational day 8 [Gd8]), as published earlier. The lungs were harvested at Gd14, 16, 19 and from neonates. Immunoblot analyses were carried out for transcription factors (oncogenic proteins, nuclear receptor, and transmembrane receptor proteins) in severely hypoplastic murine fetal lungs with coexistent diaphragmatic hernia, and results were compared with those derived from normal lungs of equivalent age. These proteins have proposed roles in the regulation of proliferation and differentiation processes of fetal lungs.
A MICROMANIPULATOR FOR EYE SURGERY

In order to facilitate surgical interventions on biological preparations on a microscopic scale, the technique known under the name of micromanipulation has been developed. The eye, which, owing to its special structure, constitutes a natural preparation chamber, would seem to be a rewarding object for the application of this technique which, in fact, has been called into use for solving a number of physiological problems. Thus, Duke-Elder (1926) used a micromanipulatory technique for inserting the cannula into arteria and vena centr. ret. , and for measuring the pressure there. Electrophysiologists, also, frequently insert their electrodes through the vitreous humour by means of some kind of manipulatory device. Now as the eye is an organ whose function may be considerably influenced even by slight surgical interventicns on microscopical structures, it would seem plausible to try to adapt the micromanipulatory technique to a practical eye-surgical method. There is ample opportunity to observe that many operative methods, theoretically well grounded and attractive from a clinical standpoint, are described and practised with highly successful results by their authors; yet they do not appear to achieve any wider measure of approval. This is presumably due to their being technically far too exacting. and to the fact that the necessary practice on an extensive material is not everywhere to be obtained. The goniotomy described by Barkan is such a method; another is the electroendothermy of Mamoli. In the first of these interventions the surgeon must, on the one hand, observe the angle of the anterior chamber by means of gonioscope and magnifying glass, and, on the other, direct his knife to bear with great accuracy to certain surmised structures in the angle of the anterior chamber. Similarly, in electroendothermy, the surgeon must examine with the ophthalmoscope and insert the diathermic needle simultaneously. These and other methods seem well adapted for transfer to a technique for use with the micromanipulator.
The long-term longitudinal course of oppositional defiant disorder and conduct disorder in ADHD boys: findings from a controlled 10-year prospective longitudinal follow-up study

Background A better understanding of the long-term scope and impact of the co-morbidity with oppositional defiant disorder (ODD) and conduct disorder (CD) in attention deficit hyperactivity disorder (ADHD) youth has important clinical and public health implications. Method Subjects were assessed blindly at baseline (mean age=10.7 years), 1-year (mean age=11.9 years), 4-year (mean age=14.7 years) and 10-year follow-up (mean age=21.7 years). The subjects' lifetime diagnostic status of ADHD, ODD and CD by the 4-year follow-up were used to define four groups (Controls, ADHD, ADHD plus ODD, and ADHD plus ODD and CD). Diagnostic outcomes at the 10-year follow-up were considered positive if full criteria were met any time after the 4-year assessment (interval diagnosis). Outcomes were examined using a Kaplan–Meier survival function (persistence of ODD), logistic regression (for binary outcomes) and negative binomial regression (for count outcomes) controlling for age. Results ODD persisted in a substantial minority of subjects at the 10-year follow-up. Independent of co-morbid CD, ODD was associated with major depression in the interval between the 4-year and the 10-year follow-up. Although ODD significantly increased the risk for CD and antisocial personality disorder, CD conferred a much larger risk for these outcomes. Furthermore, only CD was associated with significantly increased risk for psychoactive substance use disorders, smoking, and bipolar disorder. Conclusions These longitudinal findings support and extend previously reported findings from this sample at the 4-year follow-up indicating that ODD and CD follow a divergent course. They also support previous findings that ODD heralds a compromised outcome for ADHD youth grown up independently of the co-morbidity with CD.
History and Technology Developments of Radio Frequency (RF) Systems for Particle Accelerators

This article attempts to give a historical account and review of technological developments and innovations in radio frequency (RF) systems for particle accelerators. The evolution from electrostatic field to the use of RF voltage suggested by R. Wideröe made it possible to overcome the shortcomings of electrostatic accelerators, which limited the maximum achievable electric field due to voltage breakdown. After an introduction, we will provide reviews of technological developments of RF systems for particle accelerators.
Extraction, Purification, and Identification of Yersiniabactin, the Siderophore of Yersinia pestis

This unit describes in detail the extraction, purification, and identification of Yersiniabactin the siderophore of Yersinia pestis. Iron is essential for bacterial growth. Although relatively abundant, access to iron is limited in nature by low solubility. This problem is exacerbated for pathogenic bacteria, which must also defeat the host organism's innate defenses, including mechanisms to sequester iron. One solution to these problems is production of water soluble, small molecules with high affinities for iron called siderophores. This protocol has been fine tuned for Yersiniabactin purification but may be easily modified for use in isolating other siderophores or similar molecules. Curr. Protoc. Microbiol. 23:5B.3. 1‐5B.3. 22. © 2011 by John Wiley & Sons, Inc.