Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of putative virulence factors of Streptococcus pyogenes in mouse models of long-term throat colonization and pneumonia

To investigate the role of putative virulence factors of Streptococcus pyogenes (group A streptococcus; GAS) in causing disease, we introduced specific mutations in GAS strain B514, a natural mouse pathogen, and tested the mutant strains in two models of infection. To study late stages of disease, we used our previously described mouse model (C3HeB/FeJ mice) in which pneumonia and systemic spread of the streptococcus follow intratracheal inoculation. To study the early stages of disease, we report here a model of long-term (at least 21 days) throat colonization following intranasal inoculation of C57BL/10SnJ mice. When the three emm family genes of GAS strain B514-Sm were deleted, the mutant showed no significant difference from the wild type in induction of long-term throat colonization or pneumonia. We inactivated the scpA gene, which encodes a complement C5a peptidase, by insertion of a nonreplicative plasmid and found no significant difference from the wild type in the incidence of throat colonization. However, there was a small but statistically significant decrease in the incidence of pneumonia caused by the scpA mutant. Finally, we demonstrated a very important effect of the hyaluronic acid capsule in both models. Following intranasal inoculation of mice with a mutant in which a nonreplicative plasmid was inserted into the hasA gene, which encodes hyaluronate synthase, we found that all bacteria recovered from the throats of the mice were encapsulated revertants. Following intratracheal inoculation with the hasA mutant, the incidence of pneumonia within 72 h was significantly reduced from that of the control strain (P = 0.006). These results indicate that the hyaluronic acid capsule of S. pyogenes B514 confers an important selective advantage for survival of the bacteria in the upper respiratory tract and is also an important determinant in induction of pneumonia in our model system.
Ligand‐independent transforming growth factor‐β type I receptor signalling mediates type I collagen‐induced epithelial–mesenchymal transition

Evidence suggests epithelial–mesenchymal transition (EMT) as one potential source of fibroblasts in idiopathic pulmonary fibrosis. To assess the contribution of alveolar epithelial cell (AEC) EMT to fibroblast accumulation in vivo following lung injury and the influence of extracellular matrix on AEC phenotype in vitro, Nkx2.1‐Cre;mT/mG mice were generated in which AECs permanently express green fluorescent protein (GFP). On days 17–21 following intratracheal bleomycin administration, ∼4% of GFP‐positive epithelial‐derived cells expressed vimentin or α‐smooth muscle actin (α‐SMA). Primary AECs from Nkx2.1‐Cre;mT/mG mice cultured on laminin‐5 or fibronectin maintained an epithelial phenotype. In contrast, on type I collagen, cells of epithelial origin displayed nuclear localization of Smad3, acquired spindle‐shaped morphology, expressed α‐SMA and phospho‐Smad3, consistent with activation of the transforming growth factor‐β (TGFβ) signalling pathway and EMT. α‐SMA induction and Smad3 nuclear localization were blocked by the TGFβ type I receptor (TβRI, otherwise known as Alk5) inhibitor SB431542, while AEC derived from Nkx2.1‐Cre;Alk5$^{\rm{flox/KO}}$ mice did not undergo EMT on collagen, consistent with a requirement for signalling via Alk5 in collagen‐induced EMT. Inability of a pan‐specific TGFβ neutralizing antibody to inhibit effects of collagen together with absence of active TGFβ in culture supernatants is consistent with TGFβ ligand‐independent activation of Smad signalling. These results support the notion that AECs can acquire a mesenchymal phenotype following injury in vivo and implicate type I collagen as a key regulator of EMT in AECs through signalling via Alk5, likely in a TGFβ ligand‐independent manner. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Web-Based Question Answering: A Decision-Making Perspective

We investigate the use of probabilistic models and cost-benefit analyses to guide the operation of a Web-based question-answering system. We first provide an overview of research on questionanswering systems. Then, we present details about AskMSR, a prototype question-answering system that synthesizes answers from the results of queries to a Web search engine. We describe Bayesian analyses of the quality of answers generated by the system and show how we can endow the system with the ability to make decisions about the nature and number of queries that should be issued, by considering the expected value and cost of submitting the queries. Finally, we review the results of a set of experiments.
Collagen (COL4A) mutations are the most frequent mutations underlying adult focal segmental glomerulosclerosis.

BACKGROUND Multiple genes underlying focal segmental glomerulosclerosis (FSGS) and/or steroid-resistant nephrotic syndrome (SRNS) have been identified, with the recent inclusion of collagen IV mutations responsible for Alport disease (AD) or thin basement membrane nephropathy (TBMN). We aimed to investigate the distribution of gene mutations in adult patients with primary FSGS/SRNS by targeted next generation sequencing (NGS). METHODS Eighty-one adults from 76 families were recruited; 24 families had a history of renal disease. A targeted NGS panel was designed and applied, covering 39 genes implicated in FSGS/SRNS including COL4A3-5. RESULTS Confirmed pathogenic mutations were found in 10 patients (6 with family history) from 9 families (diagnostic rate 12%). Probably pathogenic mutations were identified in an additional six patients (combined diagnostic rate 20%). Definitely pathogenic mutations were identified in 22% of patients with family history and 10% without. Mutations in COL4A3-5 were present in eight patients from six families, representing 56% of definitely pathogenic mutations, and establishing a diagnosis of AD in six patients and TBMN in two patients. Collagen mutations were identified in 38% of families with familial FSGS, and 3% with sporadic FSGS, with over half the mutations occurring in COL4A5. Patients with collagen mutations were younger at presentation and more likely to have family history, haematuria and glomerular basement membrane abnormalities. CONCLUSIONS We show that collagen IV mutations, including COL4A5, frequently underlie FSGS and should be considered, particularly with a positive family history. Targeted NGS improves diagnostic efficiency by investigating many candidate genes in parallel.
Towards Wiki-based Dense City Modeling

This work reports on the advances and on the current status of a terrestrial city modeling approach, which uses images contributed by end-users as input. Hence, the Wiki principle well known from textual knowledge databases is transferred to the goal of incrementally building a virtual representation of the occupied habitat. In order to achieve this objective, many state-of-the-art computer vision methods must be applied and modified according to this task. We describe the utilized 3D vision methods and show initial results obtained from the current image database acquired by in-house participants.
Bi-Memory Model for Guiding Exploration by Pre-existing Knowledge

Reinforcement learning agents explore their environment in order to collect reward that allows them to learn what actions are good or bad in what situations. The exploration is performed using a policy that has to keep a balance between getting more information about the environment and exploiting what is already known about it. This paper presents a method for guiding exploration by pre-existing knowledge expressed by e.g. heuristic rules. A dual memory model is used where the value function is stored in long-term memory while the heuristic rules for guiding exploration act on the weights in a short-term memory. Experimental results from two “toy domains” illustrate that exploration is significantly improved when guidance can be provided by pre-existing knowledge.
Independently Evolving Species in Asexual Bdelloid Rotifers

Asexuals are an important test case for theories of why species exist. If asexual clades displayed the same pattern of discrete variation as sexual clades, this would challenge the traditional view that sex is necessary for diversification into species. However, critical evidence has been lacking: all putative examples have involved organisms with recent or ongoing histories of recombination and have relied on visual interpretation of patterns of genetic and phenotypic variation rather than on formal tests of alternative evolutionary scenarios. Here we show that a classic asexual clade, the bdelloid rotifers, has diversified into distinct evolutionary species. Intensive sampling of the genus Rotaria reveals the presence of well-separated genetic clusters indicative of independent evolution. Moreover, combined genetic and morphological analyses reveal divergent selection in feeding morphology, indicative of niche divergence. Some of the morphologically coherent groups experiencing divergent selection contain several genetic clusters, in common with findings of cryptic species in sexual organisms. Our results show that the main causes of speciation in sexual organisms, population isolation and divergent selection, have the same qualitative effects in an asexual clade. The study also demonstrates how combined molecular and morphological analyses can shed new light on the evolutionary nature of species.
Are the Con Artists Back? A Preliminary Analysis of Modern Phone Frauds

Phishing is the practice of eliciting a person's confidential information such as name, date of birth or credit card details. Typically, the phishers use simple technologies (e.g., e-mailing) to spread social engineering attacks with the goal of persuading a large amount of victims into voluntarily disclose sensitive data. Phishing based on e-mail and web technologies is certainly the most popular form. It has indeed received ample attention and some mitigation measures have been implemented. In this paper we describe our study on \emph{vishing} (voice phishing), a form of phishing where the scammers exploit the phone channel to ask for sensitive information, rather than sending e-mails and cloning trustworthy websites. In some sense, the traditional a-l\'a-Mitnick phone scams are streamlined by attackers using techniques that are typical of modern, e-mail-based phishing. We detail our analysis of an embryonic, real-world database of vishing attacks reported by victims through a publicly-available web application that we build for this purpose. The vishing activity that we registered in our preliminary analysis is targeted against the U.S. customers. According to our samples, we analyzed to what extent the criminals rely on automated responders to streamline the vishing campaigns. In addition, we analyzed the content of the conversations and found that words such as ``credit'', ``press'' (a key) or ``account'' are fairly popular. In addition, we describe the data collection infrastructure and motivate why gathering data about vishing is more difficult than for regular e-mail phishing.
Probing the reactivity of different forms of azurin by flavin photoreduction

The reactivity of a variant of the blue copper protein, azurin from Pseudomonas aeruginosa, was investigated with laser flash photolysis and compared with the reactivity of the wild‐type (WT) protein. The variant was obtained by changing the Cu ligating His117 for a glycine. The mutation creates a gap in the ligand shell of the Cu that can be filled with external ligands or water molecules. The crystal structure of the H117G variant is reported. It shows that the immediate surrounding of the Cu site in the variant exhibits less rigidity than in the WT protein and that the loop containing the Cu ligands Cys112, His117 and Met121 in the WT protein has gained flexibility in the H117G variant. Flash photolysis experiments were performed with 5‐deazariboflavin and 8α‐imidazolyl‐(N‐propylyl)‐amino riboflavin as electron donors to probe the reactivity of WT and H117G azurin, and of H117G azurin for which the gap in the Cu co‐ordination shell was filled with imidazole. 8α‐Imidazolyl‐(N‐propylyl)‐amino riboflavin appears one to two orders less efficient as a photo‐flash reductant than 5‐deazariboflavin. The reactivity of the H117G variant in the absence of external ligands appears to be 2.5‐fold lower than the WT reactivity (second‐order rate constants of 51 ± 2 × 107 m−1·s−1 versus 21 ± 1 × 107 m−1·s−1), whereas the addition of imidazole restores reactivity to above the WT level (71 ± 4 × 107 m−1·s−1). The differences are discussed in terms of structural modifications and changes in reorganizational energy and electronic coupling.
Effects and side effects of Flemish school inspection

Despite the increased importance of school inspection in recent years, the current knowledge base does not provide a clear view on the effects and side effects of being inspected. More evidence is needed in more diverse educational contexts. This article responds to this need with a quantitative study on the effects and side effects of school inspections on Flemish schools. In total 2624 respondents from 130 primary and secondary schools participated in the study. The article discusses the conceptual, instrumental, symbolic and strategic effects of inspection and its impact on self-efficacy and collective efficacy. Regarding side effects, the emotional impact is discussed alongside disturbing effects, misleading activities by schools and individual teachers and the impact on staff members’ personal lives. Furthermore the article distinguishes between the responses of staff members from schools with a positive inspection judgement and those with a less favourable judgement, and between the responses of teachers and of members of the school management teams. This study is embedded in the Flemish educational context. The results of our study are put in perspective next to results of studies in other educational contexts. Several particularities of the Flemish educational context (and how they may have affected our results) are discussed.
Newton-Krylov-Schwarz methods for Richards' equation

Abstract : This paper discusses the design and implementation of a Newton-Krylov-Schwarz solver for the implicit temporal integration on an unstructured three-dimensional spatial mesh of Richards' equation for groundwater flow in unsaturated porous media. We use aggregation techniques from the algebraic multigrid literature to construct a coarse mesh for two-level Schwarz methods. Our coarse mesh differs from other constructions in that no coarse mesh geometry need be created and we do not need geometric information about the subdomains. We report on a computational example to illustrate the performance of the preconditioner.
The effects of dynamic lighting on office workers : first-year results of a longitudinal field study

Dynamic lighting is designed to have positive effects on wellbeing and performance. In a field experiment we tested whether these effects are detectable and stable over time when employed in actual work settings. This 2-year study consists of two tranches, one following a monthly alternating experimental design, the other a yearly alternating one. This paper reports on the first tranche. In a fully counterbalanced design, office workers experienced dynamic or static lighting according to an a-b-a scheme over 3 consecutive periods (N=142, 90, and 83). Questionnaire data suggest no significant differences for need for recovery, vitality, alertness, headache and eyestrain, mental health, sleep quality, or subjective performance, although employees were more satisfied with dynamic lighting. Yet it is too early to discard the hypotheses and claims made about dynamic lighting altogether. Its effects may still emerge in environments with limited daylight, over a longer time period, or when more pronounced or differently shaped lighting patterns are applied.
Security Policy Enforcement in the OSGi Framework Using Aspect-Oriented Programming

The lifecycle mismatch between vehicles and their IT system poses a problem for the automotive industry. Such systems need to be open and extensible to provide customised functionalities and services. What is less clear is how to achieve this with quality and security guarantees. Recent studies in language-based security - the use of programming language technology to enforce application specific security policies - show that security policy enforcement mechanisms such as Mined reference monitors provide a potential solution for security in extensible systems. In this paper we study the implementation of security policy enforcement using aspect-oriented programming for the OSGi (Open Services Gateway initiative) framework. We identify classes of reference monitor-style policies that can be defined and enforced using AspectJ, a well-known aspect-oriented programming language. We demonstrate the use of security states to describe history-based policies. We also introduce and implement various levels of security states in Java to describe session level history versus global application level history. We illustrate the effectiveness of the implementation by deploying the security policy enforcement solution in an example scenario of software downloading in a standard vehicle system.
The Language of Search

This paper is concerned with a class of algorithms that perform exhaustive search on propositional knowledge bases. We show that each of these algorithms defines and generates a propositional language. Specifically, we show that the trace of a search can be interpreted as a combinational circuit, and a search algorithm then defines a propositional language consisting of circuits that are generated across all possible executions of the algorithm. In particular, we show that several versions of exhaustive DPLL search correspond to such well-known languages as FBDD, OBDD, and a precisely-defined subset of d-DNNF. By thus mapping search algorithms to propositional languages, we provide a uniform and practical framework in which successful search techniques can be harnessed for compilation of knowledge into various languages of interest, and a new methodology whereby the power and limitations of search algorithms can be understood by looking up the tractability and succinctness of the corresponding propositional languages.
The Stuff of Bits: An Essay on the Materialities of Information

An argument that the material arrangements of information -- how it is represented and interpreted -- matter significantly for our experience of information and information systems. Virtual entities that populate our digital experience, like e-books, virtual worlds, and online stores, are backed by the large-scale physical infrastructures of server farms, fiber optic cables, power plants, and microwave links. But another domain of material constraints also shapes digital living: the digital representations sketched on whiteboards, encoded into software, stored in databases, loaded into computer memory, and transmitted on networks. These digital representations encode aspects of our everyday world and make them available for digital processing. The limits and capacities of those representations carry significant consequences for digital society. In The Stuff of Bits, Paul Dourish examines the specific materialities that certain digital objects exhibit. He presents four case studies:emulation, the creation of a "virtual" computer inside another; digital spreadsheets and their role in organizational practice; relational databases and the issue of "the databaseable"; and the evolution of digital networking and the representational entailments of network protocols. These case studies demonstrate how a materialist account can offer an entry point to broader concerns -- questions of power, policy, and polity in the realm of the digital.
Agent-based network intrusion detection system using data mining approaches

Most of the existing commercial NIDS products are signature-based but not adaptive. In this paper, an adaptive NIDS using data mining technology is developed. Data mining approaches are used to accurately capture the actual behavior of network traffic, and portfolio mined is useful for differentiating "normal" and "attack" traffics. On the other hand, most of the current researches are using only one engine for detection of various attacks; the proposed system is constructed by a number of agents, which are totally different in both training and detecting processes. Each of the agents has its own strength on capturing a kind of network behavior and hence the system has strength on detecting different types of attack. In addition, its ability on detecting new types of attack as well as a higher tolerant to fluctuations were shown. The experimental results showed that the frequent patterns mined from the audit data could be used as reliable agents, which outperformed from traditional signature-based NIDS.
View-based maintenance of graphical user interfaces

One difficulty in software maintenance is that the relationship between observed program behavior and source code is not always clear. In this paper we are concerned specifically with the maintenance of graphical user interfaces (GUIs). User interface code can crosscut the decomposition of applications making GUIs hard to maintain. A popular approach to develop and maintain GUIs is to use "What you see is what you get" editors. They allow developers to work directly with a graphical design view instead of scattered source elements. Unfortunately GUI editors are limited by their ability to statically reconstruct dynamic collaborations between objects. In this paper we investigate the combination of a hybrid dynamic and static approach to allow for view-based maintenance of GUIs. Dynamic analysis reconstructs object relationships, providing a concrete context in which maintenance can be performed. Static checking restricts that only changes in the design view which can meaningfully be translated back to source are allowed. We implemented a prototype IDE plug-in and evaluate our approach by applying it to five open source projects.
Accurate identification of alternatively spliced exons using support vector machine

MOTIVATION Alternative splicing is a major component of the regulatory action on mammalian transcriptomes. It is estimated that over half of all human genes have more than one splice variant. Previous studies have shown that alternatively spliced exons possess several features that distinguish them from constitutively spliced ones. Recently, we have demonstrated that such features can be used to distinguish alternative from constitutive exons. In the current study, we used advanced machine learning methods to generate robust classifier of alternative exons. RESULTS We extracted several hundred local sequence features of constitutive as well as alternative exons. Using feature selection methods we find seven attributes that are dominant for the task of classification. Several less informative features help to slightly increase the performance of the classifier. The classifier achieves a true positive rate of 50% for a false positive rate of 0.5%. This result enables one to reliably identify alternatively spliced exons in exon databases that are believed to be dominated by constitutive exons.