Miracle-dz/UniFAR-FTUs huggingface dataset:
A New In Vivo Model to Study Protective Immunity to Zika Virus Infection in Mice With Intact Type I Interferon Signaling

The association between recent Zika virus (ZIKV) infection and neurological complications, microcephaly in the fetus, and Guillain–Barré syndrome in adults underscores the necessity for a protective vaccine. Rational vaccine development requires an in-depth understanding of the mechanisms which could protect against infection with this virus. However, so far, such an analysis has been hampered by the absence of a suitable small animal model. Unlike the situation in humans, ZIKV only replicates effectively in the peripheral organs of mice, if type I IFN signaling is interrupted. As type I IFN also impacts the adaptive immune response, mice with such a defect are not optimal for a comprehensive immunological analysis. In this report, we show that even in wild-type (WT) mice i.c. infection with low doses of virus causes marked local virus replication and lethal encephalitis in naïve mice. Furthermore, peripheral infection of WT mice with low doses of virus induces a significant immune response, which provides long-lasting protection of WT mice from a fatal outcome of subsequent i.c. challenge. Therefore, combining peripheral priming with later i.c. challenge represents a new approach for studying the adaptive immune response to ZIKV in mice with an intact type I IFN response. In this study, we focused on the mechanisms underlying resistance to reinfection. Using a combination of adoptive transfer, antibody-based cell depletion, and gene targeting, we show that the key protective factor in type I IFN replete mice is humoral immunity. CD8 T cells are not essential in mice with preformed specific antibodies, but under conditions where initial antibody levels are low, effector CD8 T cells may play a role as a back-up system. These results have important implications for our understanding of natural immunity to ZIKV infection and for Zika vaccine design.
Clustering from Multiple Uncertain Experts

Utilizing expert input often improves clustering performance. However in a knowledge discovery problem, ground truth is unknown even to an expert. Thus, instead of one expert, we solicit the opinion from multiple experts. The key question motivating this work is: which experts should be assigned higher weights when there is disagreement on whether to put a pair of samples in the same group? To model the uncertainty in constraints from different experts, we build a probabilistic model for pairwise constraints through jointly modeling each expert’s accuracy and the mapping from features to latent cluster assignments. After learning our probabilistic discriminative clustering model and accuracies of different experts, 1) samples that were not annotated by any expert can be clustered using the discriminative clustering model; and 2) experts with higher accuracies are automatically assigned higher weights in determining the latent cluster assignments. Experimental results on UCI benchmark datasets and a real-world disease subtyping dataset demonstrate that our proposed approach outperforms competing alternatives, including semi-crowdsourced clustering, semi-supervised clustering with constraints from majority voting, and consensus clustering.
FEA of Slope Failures with a Stochastic Distribution of Soil Properties Developed and Run on the Grid

This paper presents a case study about how one user developed and ran codes on a grid, in this case in the form of the National Grid Service (NGS). The user had access to the core components of the NGS which consisted of four clusters which are configured, unlike most other U.K. academic hpc services, to be used primarily through grid technologies, in this case globus. This account includes how this code was parallelised, its performance and the issues involved in selecting and using the NGS for the development and running of these codes. A general understanding of the application area, computational geotechnical engineering, and the performance issues of these codes are required to make this clear.
Minimax Embeddings

Spectral methods for nonlinear dimensionality reduction (NLDR) impose a neighborhood graph on point data and compute eigenfunctions of a quadratic form generated from the graph. We introduce a more general and more robust formulation of NLDR based on the singular value decomposition (SVD). In this framework, most spectral NLDR principles can be recovered by taking a subset of the constraints in a quadratic form built from local nullspaces on the manifold. The minimax formulation also opens up an interesting class of methods in which the graph is "decorated" with information at the vertices, offering discrete or continuous maps, reduced computational complexity, and immunity to some solution instabilities of eigenfunction approaches. Apropos, we show almost all NLDR methods based on eigenvalue decompositions (EVD) have a solution instability that increases faster than problem size. This pathology can be observed (and corrected via the minimax formulation) in problems as small as N < 100 points.
Antitumor effect of a new selective matrix metalloproteinase inhibitor, MMI‐166, on experimental pancreatic cancer

The antitumor effect of a new matrix metalloproteinase inhibitor, MMI‐166, which is a selective inhibitor of MMP‐2 and ‐9, was examined in the hamster pancreatic cancer cell line PGHAM‐1. In vitro, MMI‐166 inhibited the gelatinase activity of MMP‐2 and ‐9 derived from PGHAM‐1 cells, and dose‐dependently inhibited invasion of PGHAM‐1 through a basement membrane‐like barrier. MMI‐166 showed no apparent cytotoxicity to PGHAM‐1 cells in culture at 100 μg/ml. MMI‐166 (200 mg/kg) or vehicle were administered orally, once daily, from day 1 until day 21 after implantation in the orthotopic implantation model of PGHAM‐1. MMI‐166 significantly reduced the incidence of liver surface metastasis from 66.7% to 20.0%, and it reduced the number of liver surface metastases per animal from 6.17 to 2.00, but this reduction was not significant. MMI‐166 significantly reduced the volume of pancreatic tumors from 718.3 ± 220.0 mm3 to 222.8 ± 85.4 mm3. Treatment of pancreatic tumors with MMI‐166 caused a significant reduction in the microvessel density from 37.90 ± 10.18/mm2 to 16.16 ± 3.15/mm2 and a significant increase in apoptotic index from 1.75 ± 0.41% to 3.96 ± 0.38%, but there was no significant difference between tumor cell proliferation in the MMI‐166‐group and the control group. These results showed that selective MMP inhibition could limit both cancer spread and angiogenesis in pancreatic cancer. The selective MMP‐2 and ‐9 inhibitor MMI‐166 may be of therapeutic use in the treatment of pancreatic cancer because of its inhibitory effect on invasion and angiogenesis. © 2001 Wiley‐Liss, Inc.
QUALITY OF LIFE AFTER BILATERAL ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTIONS.

INTRODUCTION The aim of study was to analyze the influence of bilateral anterior cruciate ligament reconstructions on life quality of patients and their return to sports activities. MATERIAL AND METHODS Thirty-two operated patients took part in this survey during the period of ten years. There were 5 women and 27 men, their average age being 30.46 years (19-55). The participants answered a modified Knee Injury and Osteoarthritis Outcome Score questionnaire set and gave data about preoperative and postoperative periods. RESULTS The participants' age and parameters of Lysholm scale did not correlate significantly with the subjective level of physical activity after the second knee surgery. After the first anterior cruciate ligament reconstruction, 4 participants (12.5%) did not return to trainings, while 28 did (87.5%); 8 patients (25%) did not return to competitions and 24 of them (75%) achieved the competition level of sports activities. After the anterior cruciate ligament reconstruction of contralatera knee, 6 (18.8%) did not return to trainings, while 26 (81.3%) did; 15 patients (46.9%) did not return to competitions, while 17 (53.1% continued to compete without restrictions. The average values of questionnaire scores were between 95.1-98.2 points. Discussion and CONCLUSION Resuming the same or higher level of sports activitie. , after the first reconstruction is one of the preconditions for the same injury of another knee. An athlete looses more than two and a half years of competitions on average. Operations of additional meniscu ruptures do not play a crucial role in restitution of sports activities Although we achieved good operative results, only every seconc athlete with bilateral injury has returned to sports activities withou restrictions after the bilateral anterior cruciate reconstructions.
The Logic Programming Paradigm: A 25-Year Perspective

This exciting new text reveals both the evolution of this programming paradigm since its inception and the impressively broad scope of current research in the field. The contributors to this book are all leading world experts in Logic Programming, and they deal with both theoretical and practical issues. They address such diverse topics as: computational molecular biology, machine learning, mobile computing, multi-agent systems, planning, numerical computing and dynamical systems, database systems, an alternative to the "formulas as types" approach, program semantics and analysis, and natural language processing. XXXXXXX Neuer Text Logic Programming was founded 25 years ago. This exciting book reveals both the evolution of this programming paradigm and its impressively broad scope of current research. The contributions by leading computer scientists deal with both theoretical and practical issues. They address diverse topics such as: computational molecular biology, machine learning, mobile computing, multi-agent systems, numerical computing and dynamical systems, database systems, program semantics, natural language processing, and promising future directions.
A comparison of two immediate-early genes, c-fos and NGFI-B, as markers for functional activation in stress-related neuroendocrine circuitry

The promoter regions of the rat corticotropin-releasing factor (CRF), oxytocin (OT), and vasopressin (AVP) genes contain sequences similar to the cis-acting response element identified for NGFI-B, an immediate- early gene structurally related to the steroid hormone receptor superfamily. Combined immuno- and hybridization histochemical approaches were used to determine whether challenges that influence the synthesis and secretion of CRF, OT, and/or AVP result in altered expression in neurosecretory neurons of NGFI-B and another immediate- early gene, c-fos, which is widely used as a marker for functionally activated neurons. NGFI-B mRNA was found to be expressed at constitutively high levels in the telencephalon, but not in the endocrine hypothalamus, of unperturbed controls; basal levels of c-fos expression were uniformly low throughout the CNS. NGFI-B and c-fos mRNAs, and Fos protein, were induced with a similar time course and in similar neuroendocrine cell types in response to acute hypotensive hemorrhage (15% reduction in blood volume), intravenous injection of interleukin-1 beta (IL-1 beta; 1.87 micrograms/kg), chronic salt loading (7 d maintenance on 2% saline), and acute bilateral adrenalectomy. c-fos mRNA and Fos protein were readily demonstrable in afferent pathways that have been implicated as mediating the neuroendocrine responses in the three stress paradigms; these include medullary catecholaminergic cell groups in response to IL-1 beta and hemorrhage, and cell groups lining the lamina terminalis in response to salt loading. Challenge-specific induction of NGFI-B expression was detectable in these extrahypothalamic cell groups, though with a lesser sensitivity than that required to reveal NGFI-B induction in the hypothalamus, or c-fos expression in these related afferents. These results establish NGFI-B as a useful adjunct to c-fos, for revealing synaptic and/or transcriptional activation in the magno- and parvocellular neurosecretory systems. Differences in the sensitivity of the two markers in revealing functionally related activation in extrahypothalamic regions speak to general issues concerning the use of immediate-early genes in mapping functional circuitry in the CNS.
Development and Stem Cells Research Article

INTRODUCTION Small pools of multipotent neural progenitors give rise to a large number of neurons and glia to allow proper assembly of a functional However, as progenitors change over time to accommodate the production of different tissues, they also undergo a progressive restriction and lose their competence to produce the full assortment of cell types (Desai and McConnell, 2000; Rapaport et al., 2001). The ability to maintain progenitors in their early competent states yields the capacity to generate any desired tissue for use in future cell therapy applications. In recent years, substantial progress has been made in the identification of the factors involved in regulating progenitor competence, bringing with it the need to understand the molecular basis of their function. The identification of genes that regulate neural progenitor competence in vertebrates and insects has provided an entry point for investigating the molecular mechanism of progenitor competence (Elliott et al. The zinc-finger transcription factor Ikaros (Ik) is both necessary and sufficient to specify early progenitor competence, leading to the production of early-born cell types in the mouse retina (Elliott et al., 2008). This function of Ikaros mimics that of its Drosophila ortholog, the zinc-finger transcription factor Hunchback (Hb), which has also been shown to promote early progenitor competence during Drosophila neurogenesis (Isshiki et al., 2001; Novotny et al., 2002). Although it is known that Hb and Ik can maintain progenitor competence in the nervous system, the molecular mechanism by which they act remains unknown.
Sensitivity study of signal characteristics for an inverse waveguide based approach of material characterization

A very promising approach for the ultrasonic identification of highly damping viscoelastic polymers has been proposed by Rautenberg [1]. He uses transmission measurements through hollow cylindrical shaped test samples which are modeled as waveguides. The measurement effect relies on multiple mode-conversions at the waveguide's outer and inner boundaries and is evaluated based on an inverse approach. In this contribution we discuss different signal characteristics of the obtained dispersed signals with respect to their sensitivity to certain material parameters. Based on these sensitivities we propose a multiphase optimization scheme to increase the optimization's convergence.
Residual stress and distortion modeling of electron beam direct manufacturing Ti-6Al-4V

In this work, a finite element model is developed for predicting the thermo-mechanical response of Ti-6Al-4V during electron beam deposition. A three-dimensional thermo-elasto-plastic analysis is performed to model distortion and residual stress in the workpiece and experimental in situ temperature, and distortion measurements are performed during the deposition of a single-bead-wide, 16-layer-high wall built for model validation. Post-process blind hole–drilling residual stress measurements are also performed. Both the in situ distortion and post-process residual stress measurements suggest that stress relaxation occurs during the deposition of Ti-6Al-4V. A method of accounting for such stress relaxation in thermo-elasto-plastic simulations is proposed where both stress and plastic strain are reset to 0, when the temperature exceeds a prescribed stress relaxation temperature. Inverse simulation is used to determine the values of the absorption efficiency and the emissivity of electron beam–deposited, wire-fed Ti-6Al-4V, as well as the appropriate stress relaxation temperature.
Repeatability of lifetime exercise reporting

The purpose of the study was to determine the reliability of lifetime exercise data obtained through a structured interview. Interviews were conducted in 1992–1993 and repeated in 1997 in 150 monozygotic male twins, aged 35–69 years, from the population‐based Finnish Twin Cohort. Exercise mode, frequency, duration, intensity and period of participation were solicited for each regularly performed exercise from 12 years of age to the present. Questions related to the most common exercise mode reported in the initial interview were repeated in all subjects and the entire exercise interview was repeated in a subgroup of 38 subjects. The repeatability was highest for exercise years and mean hours/week by mode for the most commonly performed exercise (Mean ICC=0.63–0.90), and for the sum of all lifetime exercises reported (Mean ICC=0.69–0.73). The lowest repeatability was found for exercise intensity (Mean Kappa=0.33–0.48). Similarly poor reliability was found for whether or not exercise was performed at a competitive level (Mean Kappa=0.25–0.63). Overall, the structured interview of lifetime exercise was most repeatable for years of exercise and mean hours/week. Thus, these exposure variables should be considered in retrospective studies of exercise effects.
Strategy to Discriminate between High and Low Affinity Bindings of Human Immunodeficiency Virus, Type 1 Integrase to Viral DNA*

The last decade has contributed to our understanding of the three-dimensional structure of the human immunodeficiency virus, type 1 (HIV-1) integrase (IN) and to the description of how the enzyme catalyzes the viral DNA integration into the host DNA. Recognition of the viral DNA termini by IN is sequence-specific, and that of the host DNA does not require particular sequence, although in physicochemical studies IN fails to discriminate between the two interactions. Here, such discrimination was allowed thanks to a model system using designed oligonucleotides and peptides as binding structures. Spectroscopic (circular dichroism, NMR, and fluorescence anisotropy) techniques and biochemical (enzymatic and filter binding) assays clearly indicated that the amphipathic helix α4, located at the catalytic domain surface, is responsible for the specific high affinity binding of the enzyme to viral DNA. Analogues of the α4 peptide having increased helicity and still bearing the biologically relevant lysines 156 and 159 on the DNA binding face, and oligonucleotides conserving an intact attachment site, are required to achieve high affinity complexes (Kd of 1.5 nm). Data corroborate previous in vivo results obtained with mutated viruses.
Evaluation Methodologies in Information Retrieval (Dagstuhl Seminar 13441)

This report documents the program and the outcome of Dagstuhl Seminar 13441 "Evaluation Methodologies in Information Retrieval", which brought together 42 participants from 11 countries. The seminar was motivated by the fact that today's information retrieval (IR) applications can hardly be evaluated based on the classic test collection paradigm, thus there is a need for new evaluation approaches. The event started with five introductory talks on evaluation frameworks, user modeling for evaluation, evaluation criteria, measures, evaluation methodology, and new trends in IR evaluation. The seminar participants then formed working groups addressing specific aspects of IR evaluation, such as reliability and validity, task-based IR, learning as search outcome, searching for fun, IR and social media, graph search, domain-specific IR, interaction measures and models, and searcher-aware information access systems.
A two factor transformation for speaker verification through ℓ1 comparison

In a speaker verification task, speech is used as a unique biometrie identifier of an individual. A speaker presents his credentials along with a voice sample. The system matches the voice sample to its own model for the speaker to accept or reject him. This has many pitfalls. First, speech by itself, is not a sufficiently "strong" biometric, and false acceptance is a problem. Second, the user must provide the system with voice samples. This puts the speaker's privacy at risk. The system may infer personal information about the user, such as gender, age, ethnicity, health, etc. Finally, if a malicious entity pilfers the speaker's models from the system, the loss is permanent. The speaker cannot change their voice to re-enroll. In this paper, we present a two-factor transformation that addresses all the above issues. It combines a personal password with speech features in order to increase the performance of a verification system. At the same time it is guaranteed not to not reveal any information about the speech or the password to the system. Finally, it is cancelable; if a model is compromised, the user can re-enroll without risk. In particular, we study a transformation that preserves the ℓ1 distance between features as long as this is smaller than some threshold and the user uses the correct password. Experimental results confirm the theory of the proposal in term of improvement in the system's accuracy, finding conditions to get zero error. Security consequences and feasibility of its implementation are discussed.
Online Learning to Rank for Cross-Language Information Retrieval

Online learning to rank for information retrieval has shown great promise in optimization of Web search results based on user interactions. However, online learning to rank has been used only in the monolingual setting where queries and documents are in the same language. In this work, we present the first empirical study of optimizing a model for Cross-Language Information Retrieval (CLIR) based on implicit feedback inferred from user interactions. We show that ranking models for CLIR with acceptable performance can be learned in an online setting although ranking features are noisy because of the language mismatch.