Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of a cytomegalovirus vaccine: lessons from recent clinical trials

Cytomegalovirus-caused diseases are preventable. We believe that both neutralising antibodies and cell-mediated immunity are necessary for prevention. Of the CMV proteins, gB and pp65 are the minimum requirements in a vaccine to induce neutralising antibodies and cytotoxic T-lymphocyte (CTL) responses. Immunisation with additional proteins, e.g., gH, gN for neutralising antibodies and IE1exon 4 and pp150 for CTL responses, would strengthen protective immune responses. Approaches to development of a safe and effective cytomegalovirus (CMV) vaccine for the prevention of CMV diseases include: a) a live attenuated vaccine (Towne strain); b) recombinant constructs of the attenuated Towne and the virulent Toledo CMV strains; c) subunit glycoprotein B (gB) adjuvanted with MF59 to induce neutralising antibodies; d) phosphoprotein 65 (pp65) peptide-based vaccines to induce (CTL) for use in therapeutic vaccination; e) canarypox-CMV recombinants, e.g., ALVAC-CMV(gB) and ALVAC-CMV (pp65) to induce neutralising antibodies and CTL responses, respectively; f) DNA plasmids containing the genes for gB and pp65; g) dense bodies containing the key antigens. The attenuated Towne strain, gB/MF59, ALVAC-CMV(gB) and ALVAC-CMV(pp65) approaches have already been tested in clinical trials. The Towne vaccine induced neutralising antibodies and cell-mediated immunity (including CTLs) mitigated CMV disease in seronegative renal transplant recipients and protected against a low-dose virulent CMV challenge in normal volunteers but did not prevent infection in mothers of children excreting CMV. Immunisation with gB/MF59 resulted in high levels of neutralising antibodies in seronegative subjects. ALVAC-CMV(gB) did not induce neutralising antibodies but primed the immune system to a Towne strain challenge, while ALVAC-CMV(pp65) induced long-lasting CTL responses in all originally seronegative volunteers, with CTL precursor frequency similar to naturally seropositive individuals. These results suggest that CMV diseases can be prevented or attenuated and that a vaccine combining ALVAC-CMV(pp65) with gB/MF59 may induce sufficient CTLs and neutralising antibodies to protect against CMV diseases. Meanwhile, other approaches such as DNA peptide and dense body vaccines, should enter Phase I trials. All candidate vaccines will have to demonstrate that immunogenicity provides protection. Combined vaccines containing canarypox (ALVAC) vectors to express CMV-pp65 to induce CTLs and of subunit gB, given together with an appropriate adjuvant to induce neutralising antibodies, should be tested in a target population for the prevention of CMV infection and disease.
Understanding in Seeing: a discourse perspective on image metaphor

The present paper focuses on the type of metaphor known as image metaphor as it is used by architects to describe and evaluate built space in building reviews. Drawing insights from earlier research dealing with the presence and role of metaphor in a 95-text corpus, here it is suggested that image metaphor (a) motivates a large amount of architectural jargon and lexico-grammatical patterns and, therefore, can become conventionalised, (b) may involve the mapping of both images and concepts and, therefore, allows for inferencing processes, and (c) has a role at different stages of the rhetorical structure of building reviews. Together with drawing attention to the impact that the visual concerns of architects have on the metaphors articulating their thought and language, in this paper it is suggested that the differences between conceptual and image metaphors may be less dramatic than often thought, and that their characterisation cannot be effected unless the different discourse contexts where they may play a role are also taken into account.
The characterization of uncertainty for steady state multiphase flow models in pipelines

Steady state multiphase flow models are used for the design and operation of pipelines that are used in the oil and gas industry. The predictions obtained with these models contain uncertainties, which arise from model assumptions and simplifications, and from uncertainties in the input parameters. In this thesis we investigate the effect of uncertainties in the input parameters (such as the wall roughness or the superficial velocities) on two main quantities of interest in steady state multiphase flow in pipelines: the liquid holdup and the pressure drop. The approach that we take is to describe the uncertain input parameters by probability density functions (PDFs), propagate these through the steady state models, and obtain a PDF for the quantities of interest. We use two methodologies from the field of Uncertainty Quantification (UQ) to perform the propagation step: Monte Carlo sampling, the current standard in the literature, and Polynomial Chaos Expansion (PCE), our proposed approach. Furthermore, we use Sobol indices to perform a sensitivity analysis that ranks the input parameters depending on their contribution to the output. Our proposed UQ methodology is applied on two commonly used multiphase flow models in the oil and gas industry: a 0-D model, the Shell Flow Correlations (SFC), and a 1-D model, PIPESIM. First, application to the SFC reveals that PCE is much more efficient than Monte Carlo sampling, and an improvement of several orders of magnitude is achieved in terms of the number of samples required for a given accuracy, while the evaluation of a single sample requires the same computation time for the two methods. Furthermore, with UQ the flow pattern maps commonly used in industry can now be displayed in a probabilistic way. This allows the quantification of the probability that a flow regime (e.g. slug, stratified) occurs under given conditions. These are significant improvements compared to existing work that handles uncertainties in multiphase flow models. Second, application of PCE to a multiphase pipeline, known as Goldeneye, modelled in PIPESIM revealed that several uncertain variables, namely the wall roughness, the ambient temperature and the outlet pressure, play a role in determining the liquid holdup and the pressure drop. This is in contrast to what was assumed in an earlier benchmarking study. Furthermore, our probabilistic approach allows us to make predictions under uncertainty. For instance, we can now predict that the liquid holdup of the Goldeneye pipeline will have a 65% probability to be lower than the value of 1496 m3, the value obtained when using a deterministic setting.
Feature Reduction for High-Precision Text Classification

Processing high dimensional features is the key of documents analysis and text classification. Traditional technologies for selecting or extracting rely heavily on the distribution of term features in the set of documents. It generally needs high computation cost to find the significant features. In this paper, we propose a new feature reduction method based on the analysis of discriminant coefficient for text classification. The main term features called the log-scaled discriminant coefficients are designed and generated efficiently. The original feature dimension of term frequency is then converted into a small size feature set. The reduced document features are used to learn classifiers using support vector machine. The experimental results show that the proposed feature reduction approach is effectiveness in comparison with the other methods. Especially, there is an obviously great improvement in precision of text classification.
A case study for the verification of complex timed circuits: IPCMOS

The verification of a n-stage pulse-driven IPCMOS pipeline, for any n>0, is presented. The complexity of the system is 32n transistors and delay information is provided at the level of transistor The correctness of the circuit highly depends on the timed behavior of its components and the environment. To verify the system, three techniques have been combined: (1) relative-timing-based verification from absolute timing information, (2) assume-guarantee reasoning to verify untimed abstractions of timed components and (3) mathematical induction to verify pipelines of any length. Even though the circuit can interact with pulse-driven environments, the internal behavior between stages commits a handshake protocol that enables the use of untimed abstractions. The verification not only reports a positive answer about the correctness of the system, but also gives a set of sufficient relative-timing constraints that determine delay slacks under which correctness can be maintained.
Diversity Arrays Technology (DArT) for Pan-Genomic Evolutionary Studies of Non-Model Organisms

Background High-throughput tools for pan-genomic study, especially the DNA microarray platform, have sparked a remarkable increase in data production and enabled a shift in the scale at which biological investigation is possible. The use of microarrays to examine evolutionary relationships and processes, however, is predominantly restricted to model or near-model organisms. Methodology/Principal Findings This study explores the utility of Diversity Arrays Technology (DArT) in evolutionary studies of non-model organisms. DArT is a hybridization-based genotyping method that uses microarray technology to identify and type DNA polymorphism. Theoretically applicable to any organism (even one for which no prior genetic data are available), DArT has not yet been explored in exclusively wild sample sets, nor extensively examined in a phylogenetic framework. DArT recovered 1349 markers of largely low copy-number loci in two lineages of seed-free land plants: the diploid fern Asplenium viride and the haploid moss Garovaglia elegans. Direct sequencing of 148 of these DArT markers identified 30 putative loci including four routinely sequenced for evolutionary studies in plants. Phylogenetic analyses of DArT genotypes reveal phylogeographic and substrate specificity patterns in A. viride, a lack of phylogeographic pattern in Australian G. elegans, and additive variation in hybrid or mixed samples. Conclusions/Significance These results enable methodological recommendations including procedures for detecting and analysing DArT markers tailored specifically to evolutionary investigations and practical factors informing the decision to use DArT, and raise evolutionary hypotheses concerning substrate specificity and biogeographic patterns. Thus DArT is a demonstrably valuable addition to the set of existing molecular approaches used to infer biological phenomena such as adaptive radiations, population dynamics, hybridization, introgression, ecological differentiation and phylogeography.
Optical Fiber Networks for Remote Fiber Optic Sensors

This paper presents an overview of optical fiber sensor networks for remote sensing. Firstly, the state of the art of remote fiber sensor systems has been considered. We have summarized the great evolution of these systems in recent years; this progress confirms that fiber-optic remote sensing is a promising technology with a wide field of practical applications. Afterwards, the most representative remote fiber-optic sensor systems are briefly explained, discussing their schemes, challenges, pros and cons. Finally, a synopsis of the main factors to take into consideration in the design of a remote sensor system is gathered.
Thoracic gamma irradiation-induced obesity in C57BL/6 female mice

Abstract Purpose: To investigate the late effects of thoracic region irradiation (TRI) on mouse body weight. Materials and methods: Female C57BL/6 mice were divided into nonirradiated, 5 Gy total body irradiation, 9 Gy sub-total body irradiation, and 12.5 Gy thoracic region irradiation (TRI) groups. Changes in mouse weight were monitored every other week at similar time points for 12 months. The anatomical characteristics of abdominal visceral fat distribution were recorded, and mitochondrial DNA copy number in the hearts and livers and lipid metabolic signaling in the liver were analyzed. Data were analyzed by one-way analysis of variance and a student’s t-test. Results: TRI led to a significant increase (p < .001) in body weight that was dependent on time and individuals [42.1% of mice were overweight (50% increase in body weight) 4 months post-TRI and 100% of mice were overweight at 10 months post-TRI]. Gross anatomical features of abdominal visceral fat distribution and storage in radiation-induced overweight/severely overweight mice were similar to those of high fat diet-induced overweight/severely overweight mice. The mitochondrial genome of heart and liver tissues from overweight/severely overweight mice had significantly (p < .05) decreased functional mitochondrial DNA copy number (ratios decreased from 1 to 0.71 or 0.49, respectively) and significantly (p < .05) increased mitochondrial DNA mutations (ratios increased from 1 to 3.21 or 1.83, respectively). CPT1 and IRS2 lipid metabolic signaling was significantly (p < .05–.01) decreased for both mRNA (fold decrease from 1 to 0.60 or 0.55, respectively) and protein (fold decrease from 1 to 0.62 or 0.19, respectively). Conclusions: TRI can cause mice to gain weight. These findings indicate that TRI can result in lipid metabolic abnormalities and provide a model to study the factors that result in these abnormalities.
Using Convolutional Neural Networks and Transfer Learning to Perform Yelp Restaurant Photo Classification

For the Yelp Image Classification Kaggle Challenge, we use a modified VGGNet to make predictions on 9 specific attributes of restaurants based on images by performing transfer learning. We explore two approaches to making these predictions: a naive model that assigns the attributes of the restaurant to each picture, and a more sophisticated method called multiple instance learning. With our naive model, we achieved a mean F1 score of 0.533, while our MIL model achieved a mean F1 score of 0.618. We then explore and evaluate other past methods attempted for this challenge and note various methods of improvement on our current models.
Impact neighborhood indexing (INI) in diffusion graphs

A graph neighborhood consists of a set of nodes that are nearby or otherwise related to each other. While existing definitions consider the structure (or topology) of the graph, we note that they fail to take into account the information propagation and diffusion characteristics, such as decay and reinforcement, common in many networks. In this paper, we first define the propagation efficiency of nodes and edges. We use this to introduce the novel concept of zero-erasure (or impact) neighborhood (ZEN) of a given node, n, consisting of the set of nodes that receive information from (or are impacted by) n without any decay. Based on this, we present an impact neighborhood indexing (INI) algorithm that creates data structures to help quickly identify impact neighborhood of any given node. Experiment results confirm the efficiency and effectiveness of the proposed INI algorithms.
Moving the Weber Fraction: The Perceptual Precision for Moment of Inertia Increases with Exploration Force

How does the magnitude of the exploration force influence the precision of haptic perceptual estimates? To address this question, we examined the perceptual precision for moment of inertia (i.e., an object's “angular mass”) under different force conditions, using the Weber fraction to quantify perceptual precision. Participants rotated a rod around a fixed axis and judged its moment of inertia in a two-alternative forced-choice task. We instructed different levels of exploration force, thereby manipulating the magnitude of both the exploration force and the angular acceleration. These are the two signals that are needed by the nervous system to estimate moment of inertia. Importantly, one can assume that the absolute noise on both signals increases with an increase in the signals' magnitudes, while the relative noise (i.e., noise/signal) decreases with an increase in signal magnitude. We examined how the perceptual precision for moment of inertia was affected by this neural noise. In a first experiment we found that a low exploration force caused a higher Weber fraction (22%) than a high exploration force (13%), which suggested that the perceptual precision was constrained by the relative noise. This hypothesis was supported by the result of a second experiment, in which we found that the relationship between exploration force and Weber fraction had a similar shape as the theoretical relationship between signal magnitude and relative noise. The present study thus demonstrated that the amount of force used to explore an object can profoundly influence the precision by which its properties are perceived.
A 500 MHz, 68% efficient, fully on-die digitally controlled buck Voltage Regulator on 22nm Tri-Gate CMOS

A fully on-die, digitally controlled, 500MHz switching, 250mA rated output buck Voltage Regulator (VR) implemented in 22nm Tri-Gate CMOS is presented. The silicon measured a peak efficiency of 68% and consumed an area of 0.6mm2 (without output decoupling) with a power density of about 410 mW/mm2. The paper also demonstrates a controller bandwidth of 43MHz; the highest reported to date for any digital controller, resulting in output voltage ramp rates as high as 10V/μsec.
Statistical Consistency of Ranking Methods in A Rank-Differentiable Probability Space

This paper is concerned with the statistical consistency of ranking methods. Recently, it was proven that many commonly used pairwise ranking methods are inconsistent with the weighted pairwise disagreement loss (WPDL), which can be viewed as the true loss of ranking, even in a low-noise setting. This result is interesting but also surprising, given that the pairwise ranking methods have been shown very effective in practice. In this paper, we argue that the aforementioned result might not be conclusive, depending on what kind of assumptions are used. We give a new assumption that the labels of objects to rank lie in a rank-differentiable probability space (RDPS), and prove that the pairwise ranking methods become consistent with WPDL under this assumption. What is especially inspiring is that RDPS is actually not stronger than but similar to the low-noise setting. Our studies provide theoretical justifications of some empirical findings on pairwise ranking methods that are unexplained before, which bridge the gap between theory and applications.
The Intestine Plays a Substantial Role in Human Vitamin B6 Metabolism: A Caco-2 Cell Model

Background Vitamin B6 is present in various forms (vitamers) in the diet that need to be metabolized to pyridoxal phosphate (PLP), the active cofactor form of vitamin B6. In literature, the liver has been reported to be the major site for this conversion, whereas the exact role of the intestine remains to be elucidated. Objective To gain insight into the role of the intestine in human vitamin B6 metabolism. Materials and Methods Expression of the enzymes pyridoxal kinase (PK), pyridox(am)ine phosphate oxidase (PNPO) and PLP-phosphatase was determined in Caco-2 cells and in lysates of human intestine. Vitamin B6 uptake, conversion and excretion were studied in polarized Caco-2 cell monolayers. B6 vitamer concentrations (pyridoxine (PN), pyridoxal (PL), PLP, pyridoxamine (PM), pyridoxamine phosphate (PMP)) and pyridoxic acid (PA) were quantified by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) using stable isotope-labeled internal standards. Results The enzymatic system involved in vitamin B6 metabolism (PK, PNPO and PLP-phosphatase) is fully expressed in Caco-2 cells as well as in human intestine. We show uptake of PN, PM and PL by Caco-2 cells, conversion of PN and PM into PL and excretion of all three unphosphorylated B6 vitamers. Conclusion We demonstrate, in a Caco-2 cell model, that the intestine plays a substantial role in human vitamin B6 metabolism.
Biology and treatment of childhood T-lineage acute lymphoblastic leukemia.

ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) is the most prevalent type of cancer, as well as the most common form of leukemia in children. [1][1] This lymphoid malignancy, manifested by the proliferation of lymphopoietic blast cells, represents a heterogeneous group of diseases that vary with respect to
ServerCast: efficient cooperative bulk data distribution scheme for content distribution networks

We study bulk data distribution schemes for content distribution networks (CDNs) using application-level overlay. Given the outbound bandwidth of all the CDN edge servers, a fluid-flow based analytical model is constructed to derive the optimal bandwidth allocations at the origin server and among all the edge servers. From which, a lower bound on the content update time is obtained. In order to have an efficient and practical scheme for bulk data distribution, ServerCast is designed to take advantages of the analytical results. Simulations are conducted to evaluate the performance of ServerCast. We show that ServerCast not only outperforms the two existing schemes, fastreplica and multiple unicast, but also yields a content update time within 18% of the derived lower bound.
Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis

BIBF 1000 is a small molecule inhibitor targeting the receptor kinases of platelet-derived growth factor (PDGF), basic fibroblast growth factor and vascular endothelial growth factor, which have known roles in the pathogenesis of pulmonary fibrosis. The anti-fibrotic potential of BIBF 1000 was determined in a rat model of bleomycin-induced lung fibrosis and in an ex vivo fibroblast differentiation assay. Rats exposed to a single intra-tracheal injection of bleomycin were treated with BIBF 1000 starting 10 days after bleomycin administration. To gauge for anti-fibrotic activity, collagen deposition and pro-fibrotic growth factor gene expression was analysed in isolated lungs. Furthermore, the activity of BIBF 1000 was compared with imatinib mesylate (combined PDGF receptor, c-kit and c-abl kinase inhibitor) and SB-431542 (transforming growth factor (TGF)-β receptor I kinase inhibitor) in an ex vivo TGF-β-driven fibroblast to myofibroblast differentiation assay, performed in primary human bronchial fibroblasts. Treatment of rats with BIBF 1000 resulted in the attenuation of fibrosis as assessed by the reduction of collagen deposition and the inhibition of pro-fibrotic gene expression. In the cellular assay both SB-431542 and BIBF 1000 showed dose-dependent inhibition of TGF-β-induced differentiation, whereas imatinib mesylate was inactive. BIBF 1000, or related small molecules with a similar kinase inhibition profile, may represent a novel therapeutic approach for the treatment of idiopathic pulmonary fibrosis.