Miracle-dz/UniFAR-FTUs huggingface dataset:
High resolution analysis of cellular immune responses in resolved and persistent hepatitis C virus infection.

BACKGROUND & AIMS Cellular immune responses are thought to play a key role in the resolution of primary HCV infection. Although it has been consistently shown that CD4+ T-cell responses are maintained in those with spontaneous resolution but lost in those with persistent infection, the role of CD8+ T-cell responses remains controversial. Previous studies have largely focused on limited HLA alleles and predefined CD8+ T-cell epitopes, and, thus, comprehensive studies remain to be performed. METHODS To understand the composition of the immune response associated with spontaneous resolution, we comprehensively mapped CD8+ T-cell responses in 20 HLA-diverse persons with resolved HCV infection, using HCV peptides spanning the entire genome. We analyzed the magnitude, breadth, function, and phenotype using ELISpot, class-I tetramers, intracellular cytokine staining, and cytolytic assays. We studied in parallel HCV-specific responses and viral sequence variation in persistent infection. RESULTS Responses in individuals with resolved infection were strong and broad with robust proliferation in response to antigen. Responses in those persistently infected were rarely detected ex vivo and, when present, were narrowly directed and weak. However, they also proliferated in vitro. Dominant target epitopes differed among individuals in both cohorts, despite frequently shared HLA-alleles. CONCLUSIONS These data indicate that persisting, strong CD8+ T-cell responses are observed in the majority of persons with resolved HCV infection and provide support for strategies to boost CD8+ T-cell responses for the prevention or treatment of HCV infection but also highlight the diversity of responses that may need to be elicited to provide protection.
Using Semantic Web Tools for Context Interchange

The Context Interchange Strategy (COIN) is an approach to solving the problem of interoperability of semantically heterogeneous data sources through context mediation. The existing implementation of COIN uses its own notation and syntax for representing ontologies. More recently, the OWL Web Ontology Language is becoming established as the W3C recommended ontology language. A bridge is needed between these two areas and an explanation on how each of the two approaches can learn from each other. We propose the use of the COIN strategy to solve context disparity and ontology interoperability problems in the emerging Semantic Web both at the ontology level and at the data level. In this work we showcase how the problems that arise from context-dependent representation of facts can be mitigated by Semantic Web techniques, as tools of the conceptual framework developed over 15 years of COIN research.
The specific recognition by macrophages of CD8+,CD45RO+ T cells undergoing apoptosis: a mechanism for T cell clearance during resolution of viral infections

During viral infections, CD8+,CD45RO+ T populations expand. These primed cells express abundant levels of cytoplasmic granules that contain perforin and TIA-1. Recent work has suggested that the majority of this CD8+ population downregulates Bcl-2 protein expression and is destined to undergo apoptosis. In this study we have investigated the elimination of these apoptotic CD8+ T cells by both human monocyte- derived and murine bone marrow macrophages. We have found that these phagocytes recognize and ingest both apoptotic CD8+ and CD4+ T cells using an alpha v beta 3 (vitronectin receptor)/CD36/thrombospondin recognition system, with the same receptors being used in the recognition of apoptotic neutrophils. These data provide new evidence for a mechanism that enables the clearance of greatly increased populations of CD8+ effector cells which are found during viral infections. This enables cellular homeostasis to occur in the host upon resolution of viral diseases in vivo.
Enhanced challenge-response set and secure usage scenarios for ordering-based ring oscillator-physical unclonable functions

The number of applicable challenge–response pairs (CRPs) in physical unclonable functions (PUFs) is critical especially for authentication protocols in security systems. Ideally, full read-out of all CRPs should be infeasible and CRPs should be independent from each other for a highly secure system. CRP concept is not defined in ordering-based ring oscillator (RO) PUFs presented in the literature. In this paper, the authors propose two methods for enhanced CRP set in ordering-based RO-PUFs and analyse their performance in terms of uniqueness and area efficiency. Next, they propose three secure usage scenarios based on enhanced CRP set methods, preventing the CRPs from leaking information about each other. With the proposed systems, 100% robust, area and power efficient and secure PUF structures with exponential number of CRPs become possible that are very convenient especially for authentication protocols.
The Role of Design Thinking and Physical Prototyping in Social Software Engineering

Social Software Engineering (Social SE), that is SE aiming to promote positive social change, is a rapidly emerging area. Here, software and digital artefacts are seen as tools for social change, rather than end products or 'solutions'. Moreover, Social SE requires a sustained buy-in from a range of stakeholders and end-users working in partnership with multidisciplinary software development teams often at a distance. This context poses new challenges to software engineering: it requires both an agile approach for handling uncertainties in the software development process, and the application of participatory, creative design processes to bridge the knowledge asymmetries and the geographical distances in the partnership. This paper argues for the role of design thinking in Social SE and highlights its implications for software engineering in general. It does so by reporting on the contributions that design thinking - and in particular physical design - has brought to (1) the problem space definition, (2) user requirements capture and (3) system feature design of a renewable energy forecasting system developed in partnership with a remote Scottish Island community.
Real-time parallel distributed compensation of an inverted pendulum via exact Takagi-Sugeno models

This paper presents simulation and real-time results of a fuzzy control scheme better known as parallel distributed compensation (PDC) for stabilization of an inverted pendulum on a cart. In contrast with traditional fuzzy schemes, the nonlinear model of the plant is fully taken into account for control design. The nonlinear model is recast as an exact convex sum of linear models via the sector nonlinearity approach; the resulting structure fits the class of the well-known Takagi-Sugeno (TS) models. Control laws are thus derived by means of the direct Lyapunov method, which along with the model convexity produce conditions in the form of linear matrix inequalities (LMIs). In contrast with PID tuning techniques, LMI conditions are optimally solved by commercially available software and allow a natural inclusion of specifications on input/output constraints and convergence rate. Simulation as well as real-time implementation issues are discussed.
Random projection based clustering for population genomics

Recent data revolution in population genomics for bacteria has increased the size of aligned sequence data sets by two-to-three orders of magnitude. This trend is expected to continue in the near future, putting an emphasis on applicability of big data techniques to leverage biologically important insights. Moreover, with the increasing density of sampling, it may also be necessary to consider alignment-free sequence analysis techniques combined with clustering to yield a sufficient insight to data. This leads to ultra high-dimensional data with tens of millions of variables, which can no longer be handled by the existing population genomic methods. Using the largest bacterial sequence data sets published to date, we demonstrate that random projection based clustering provides a highly accurate and several orders of magnitude faster approach to the analysis of both alignment-based and alignment-free genome data sets, compared with the Bayesian model-based analysis that is currently considered as the state-of-the-art. Hence, clustering methods for big data harbor considerable potential for important applications in genomics and could pave way for novel analysis pipelines even in the online setting when executed in a massively parallel computing environment.
Structural Intervention Distance for Evaluating Causal Graphs

Abstract Causal inference relies on the structure of a graph, often a directed acyclic graph (DAG). Different graphs may result in different causal inference statements and different intervention distributions. To quantify such differences, we propose a (pre-)metric between DAGs, the structural intervention distance (SID). The SID is based on a graphical criterion only and quantifies the closeness between two DAGs in terms of their corresponding causal inference statements. It is therefore well suited for evaluating graphs that are used for computing interventions. Instead of DAGs, it is also possible to compare CPDAGs, completed partially DAGs that represent Markov equivalence classes. The SID differs significantly from the widely used structural Hamming distance and therefore constitutes a valuable additional measure. We discuss properties of this distance and provide a (reasonably) efficient implementation with software code available on the first author’s home page.
Multilaboratory Testing of Two-Drug Combinations of Antifungals against Candida albicans, Candida glabrata, and Candida parapsilosis

ABSTRACT There are few multilaboratory studies of antifungal combination testing to suggest a format for use in clinical laboratories. In the present study, eight laboratories tested quality control (QC) strain Candida parapsilosis ATCC 22019 and clinical isolates Candida albicans 20533.043, C. albicans 20464.007, Candida glabrata 20205.075, and C. parapsilosis 20580.070. The clinical isolates had relatively high azole and echinocandin MICs. A modified CLSI M27-A3 protocol was used, with 96-well custom-made plates containing checkerboard pairwise combinations of amphotericin B (AMB), anidulafungin (AND), caspofungin (CSP), micafungin (MCF), posaconazole (PSC), and voriconazole (VRC). The endpoints were scored visually and on a spectrophotometer or enzyme-linked immunosorbent assay (ELISA) reader for 50% growth reduction (50% inhibitory concentration [IC50]). Combination IC50s were used to calculate summation fractional inhibitory concentration indices (FICIs) (ΣFIC) based on the Lowe additivity formula. The results revealed that the IC50s of all drug combinations were lower or equal to the IC50 of individual drugs in the combination. A majority of the ΣFIC values were indifferent (ΣFIC = 0.51 to 2.0), but no antagonism was observed (ΣFIC ≥ 4). Synergistic combinations (ΣFIC ≤ 0.5) were found for AMB-PSC against C. glabrata and for AMB-AND and AMB-CSP against C. parapsilosis by both visual and spectrophotometric readings. Additional synergistic interactions were revealed by either of the two endpoints for AMB-AND, AMB-CSP, AMB-MCF, AMB-PSC, AMB-VRC, AND-PSC, CSP-MCF, and CSP-PSC. The percent agreements among participating laboratories ranged from 37.5% (lowest) for AND-CSP and POS-VOR to 87.5% (highest) for AMB-MCF and AND-CSP. Median ΣFIC values showed a wide dispersion, and interlaboratory agreements were less than 85% in most instances. Additional studies are needed to improve the interlaboratory reproducibility of antifungal combination testing.
Unraveling Additional O-Methylation Steps in Benzylisoquinoline Alkaloid Biosynthesis in California Poppy (Eschscholzia californica)

California poppy (Eschscholzia californica), a member of the Papaveraceae family, produces many biologically active benzylisoquinoline alkaloids (BIAs), such as sanguinarine, macarpine and chelerythrine. Sanguinarine biosynthesis has been elucidated at the molecular level, and its biosynthetic genes have been isolated and used in synthetic biology approaches to produce BIAs in vitro. However, several genes involved in the biosynthesis of macarpine and chelerythrine have not yet been characterized. In this study, we report the isolation and characterization of a novel O-methyltransferase (OMT) involved in the biosynthesis of partially characterized BIAs, especially chelerythrine. A search of the RNA sequence database from NCBI and PhytoMetaSyn for the conserved OMT domain identified 68 new OMT-like sequences, of which the longest 22 sequences were selected based on sequence similarity. Based on their expression in cell lines with different macarpine/chelerythrine profiles, we selected three OMTs (G2, G3 and G11) for further characterization. G3 expression in Escherichia coli indicated O-methylation activity of the simple benzylisoquinolines, including reticuline and norreticuline, and the protoberberine scoulerine with dual regio-reactivities. G3 produced 7-O-methylated, 3'-O-methylated and dual O-methylated products from reticuline and norreticuline, and 9-O-methylated tetrahydrocolumbamine, 2-O-methylscoulerine and tetrahydropalmatine from scoulerine. Further enzymatic analyses suggested that G3 is a scoulerine-9-O-methyltransferase for the biosynthesis of chelerythrine in California poppy. In the present study, we discuss the physiological role of G3 in BIA biosynthesis.
Preference for Well-Balanced Saliency in Details Cropped from Photographs

Photographic cropping is the act of selecting part of a photograph to enhance its aesthetic appearance or visual impact. It is common practice with both professional (expert) and amateur (non-expert) photographers. In a psychometric study, McManus et al. (2011b) showed that participants cropped photographs confidently and reliably. Experts tended to select details from a wider range of positions than non-experts, but other croppers did not generally prefer details that were selected by experts. It remained unclear, however, on what grounds participants selected particular details from a photograph while avoiding other details. One of the factors contributing to cropping decision may be visual saliency. Indeed, various saliency-based computer algorithms are available for the automatic cropping of photographs. However, careful experimental studies on the relation between saliency and cropping are lacking to date. In the present study, we re-analyzed the data from the studies by McManus et al. (2011a,b), focusing on statistical image properties. We calculated saliency-based measures for details selected and details avoided during cropping. As expected, we found that selected details contain regions of higher saliency than avoided details on average. Moreover, the saliency center-of-mass was closer to the geometrical center in selected details than in avoided details. Results were confirmed in an eye tracking study with the same dataset of images. Interestingly, the observed regularities in cropping behavior were less pronounced for experts than for non-experts. In summary, our results suggest that, during cropping, participants tend to select salient regions and place them in an image composition that is well-balanced with respect to the distribution of saliency. Our study contributes to the knowledge of perceptual bottom-up features that are germane to aesthetic decisions in photography and their variability in non-experts and experts.
Visually Augmented POMDP for Indoor Robot Navigation

This paper presents a new approach to robustly track a robot’s location in indoor environments using a partially observable Markov model. This model is constructed from topological representation of the environment, plus actuator an sensor characteristics. The system takes into account various sources of uncertainty to maintain a probability distribution over all possible locations of the robot. A novel feature of our approach is the integration of visual information to augment the robustness of the system. We show the first results of this approach in localizing an actual mobile robot navigating corridors.
Action and cognition. Cognitive and motor Skills in a developmental perspective

In this chapter we discuss the relationships between motor and cognitive skills in a developmental perspective, usually considered as two separate categories of behavior. We have try to demonstrate that the processes and mechanisms underlying motor and cognitive skills have similarities. For the purpose of this chapter, we have considered cognitive and motor skills separately. Particular attention will be paid to "seriation skills", from both a motor point of view and a cognitive one. A large number of studies have been done from the cognitive point of view in order to discover how children succeed in seriating objects or events according to a given property (size, weight, etc.). We have studied, from a motor point of view, how children manage to adjust certain parameters of their actions (velocity, amplitude, force, etc) in relation to the variations of different properties of the objects. The major problem is to know whether plans (cognitive labels) and programs (motor labels) have the same underlying mechanisms or whether, on the contrary, they have different kinds of processing systems.
Review Article

The publication of Geneviève Sellier and Noël Burch’s La Drôle de guerre des sexes du cinéma français in 1996 marked a turning point in French cinema studies by bringing gender to the fore as a category of analysis and by blending sociology with the structuralist and psychoanalytical approaches that had dominated the discipline during the 1970s and ’80s. In so doing, the book complemented a parallel wave of interpretative and methodological revisionism already well underway in the field of history (Scott 1988; Hunt 1991, 1992). In particular, La Drôle de guerre des sexes provided a basis for rethinking aesthetically-constituted categories such as poetic realism by refuting the longstanding claim that there was an essential thematic and formal continuity between French cinema of the 1930s and that of the Occupation (Jeancolas 1983; Garçon 1984). Instead, Sellier and Burch argued compellingly that the symbolic emasculation of France in 1940 at the hands of the Germans and the hypertraditionalist gender politics of the Vichy regime prompted a radical shift in cinema’s representation of male/female power relations, with the seemingly unshakeable authority of pre-war patriarchs usurped by proactive, often dangerous younger women. Though the authors’ French peers were slow to build on their pioneering work, Anglophone scholars embraced gender and interdisciplinarity as tools for rethinking the
Associations between socioeconomic status and cortical thickness in prefrontal cortical subregions

Childhood socioeconomic status (SES) is highly predictive of a wide range of life outcomes, ranging from cognitive ability and academic achievement to physical and mental health. Recent work investigating more specific correlates of SES has identified SES disparities in executive function performance and measures of prefrontal cortical function, but little is known about the structural correlates of childhood socioeconomic status. Structural MRI and demographic data from a sample of 283 healthy children in the first wave of the NIH MRI Study of Normal Brain Development were used to systematically investigate the relationship between SES and frontal cortical thickness. Specifically, we assessed the association between two principal measures of childhood SES, family income and parental education, on grey matter thickness in specific subregions of prefrontal cortex and on the asymmetry of these areas. After correcting for multiple comparisons and controlling for potentially confounding variables, parental education significantly predicted cortical thickness in the right anterior cingulate gyrus and left superior frontal gyrus. These results suggest that brain structure in frontal regions may provide a meaningful link between SES and cognitive function among healthy, typically developing children. 3 There is a clear link between socioeconomic status (SES) and cognitive outcomes: children who grow up in poverty tend to have lower IQs and academic achievement scores, are less likely to graduate high school, and are less likely to develop basic reading and mathematics proficiency than their higher-clinically meaningful, reflect the combined influence of many specific neurocognitive systems. It is these underlying systems that mediate the association between SES and cognitive performance and provide possible targets for interventions designed to reduce SES disparities. The methods of cognitive neuroscience, such as neuropsychological testing and structural brain imaging, may make it possible to identify specific neurocognitive systems that vary along socioeconomic gradients. The goal of the present study is to investigate the relation between SES and prefrontal cortical thickness in healthy normal children. We focus on prefrontal cortex for three reasons. First, this brain region is essential for executive function, which is associated with academic environmental factors including stress (McEwen & Gianaros, 2011), suggest that differences in the experiences of lower and higher SES children could impact prefrontal development. Third, and most directly relevant, many studies have found SES differences in executive function and in prefrontal activity. In children ranging from infancy to adolescence, SES has been found to correlate with executive function as measured by many …
Tracking cyclones in regional model data: the future of Mediterranean storms

Abstract. With the advent of regional climate modelling, there are high-resolution data available for regional climatological change studies. Automatic tracking of cyclones in these datasets encounters problems with high spatial resolution due to cyclone substructure. Watershed segmentation, a technique from image analysis, has been used to obtain estimates for the spatial extent of cyclones, enabling better tracking and precipitation analysis. In this study we have used data from a 0.5° Regional Model (REMO) climatological model run for the period from 1961-2099, following the International Panel on Climate Change Special Report on Emissions Scenarios (IPCC SRES) B2 forcing. The resulting hourly mean sea level pressure (MSLP) fields have been analysed for cyclone numbers and tracks in the Mediterranean region. According to the results, the total number of cyclones in the Mediterranean seems to be increasing in the future, in spite of a general decrease of the numbers of stronger systems. In Summer, the increase in each gridbox seems to be proportional to the total number of cyclones in that box, whereas in Winter there is a slight proportional decrease. As concerns track properties and precipitation estimates along tracks, no significant change could be detected.
Preconditioned Low-Rank Methods for High-Dimensional Elliptic PDE Eigenvalue Problems

Abstract We consider elliptic PDE eigenvalue problems on a tensorized domain, discretized such that the resulting matrix eigenvalue problem Ax=λx exhibits Kronecker product structure. In particular, we are concerned with the case of high dimensions, where standard approaches to the solution of matrix eigenvalue problems fail due to the exponentially growing degrees of freedom. Recent work shows that this curse of dimensionality can in many cases be addressed by approximating the desired solution vector x in a low-rank tensor format. In this paper, we use the hierarchical Tucker decomposition to develop a low-rank variant of LOBPCG, a classical preconditioned eigenvalue solver. We also show how the ALS and MALS (DMRG) methods known from computational quantum physics can be adapted to the hierarchical Tucker decomposition. Finally, a combination of ALS and MALS with LOBPCG and with our low-rank variant is proposed. A number of numerical experiments indicate that such combinations represent the methods of choice.