Miracle-dz/UniFAR-FTUs huggingface dataset:
Observer variability in the interpretation of HER2/neu immunohistochemical expression with unaided and computer-aided digital microscopy.

CONTEXT Observer variability in digital microscopy and the effect of computer-aided digital microscopy are underexamined areas in need of further research, considering the increasing use and future role of digital imaging in pathology. A reduction in observer variability using computer aids could enhance the statistical power of studies designed to determine the utility of new biomarkers and accelerate their incorporation in clinical practice. OBJECTIVES To quantify interobserver and intraobserver variability in immunohistochemical analysis of HER2/neu with digital microscopy and computer-aided digital microscopy, and to test the hypothesis that observer agreement in the quantitative assessment of HER2/neu immunohistochemical expression is increased with the use of computer-aided microscopy. DESIGN A set of 335 digital microscopy images extracted from 64 breast cancer tissue slides stained with a HER2 antibody, were read by 14 observers in 2 reading modes: the unaided mode and the computer-aided mode. In the unaided mode, HER2 images were displayed on a calibrated color monitor with no other information, whereas in the computer-aided mode, observers were shown a HER2 image along with a corresponding feature plot showing computer-extracted values of membrane staining intensity and membrane completeness for the particular image under examination and, at the same time, mean feature values of the different HER2 categories. In both modes, observers were asked to provide a continuous score of HER2 expression. RESULTS Agreement analysis performed on the output of the study showed significant improvement in both interobserver and intraobserver agreement when the computer-aided reading mode was used to evaluate preselected image fields. CONCLUSION The role of computer-aided digital microscopy in reducing observer variability in immunohistochemistry is promising.
UVA-340 as Energy Source, Mimicking Natural Sunlight, Activates the Transcription Factor AP-1 in Cultured Fibroblasts: Evidence for Involvement of Protein Kinase-C¶

Abstract Ultraviolet radiation (UVR) is known to affect a variety of cellular functions, including gene expression. A number of signaling pathways have been suggested to mediate these effects, including the participation of activator protein-1 (AP-1), activator protein-2 (AP-2) and nuclear factor-κB (NF-κB). The divergent results from previous studies could be explained, at least in part, by the source of UVR with different spectral characteristics as well as the type of cells employed as targets. In this study we have utilized UVA-340 as an energy source with output which closely matches the spectrum of natural sunlight over the range of 295–350 nm for irradiation of cultured fibroblasts. Combination of electrophoretic mobility shift assays and Northern analyses revealed activation of AP-1 but not NF-κB or AP-2. Inhibition studies further suggested the participation of protein kinase-C, but not protein kinase-A, and that an inhibitor of mitogen-activated protein kinase (MEK-1/2) did not alter the AP-1 activation. Free radical quenchers, sodium azide and N-acetylcysteine, did not affect the AP-1 binding activity. Finally, UVA-340 was shown to enhance transcriptional expression of the type-VII collagen gene (COL7A1), which is endogenously expressed in dermal fibroblast in an AP-1 dependent manner. Introduction of a mutation into the AP-1 site of the COL7A1 promoter abolished this activation. Thus, our results obtained by utilizing a novel energy source, UVA-340, mimicking natural sunlight at UVB and lower UVA range indicate a role for AP-1 in mediating the enhanced gene expression by UVR. Collectively, these results suggest that AP-1 is an important mediator of UVR action in fibroblasts.
Expert Systems With Applications

Argumentation mining is a recent challenge concerning the automatic extraction of arguments from unstructured textual corpora. Argumentation mining technologies are rapidly evolving and show a clear potential for application in diverse areas such as recommender systems, policy-making and the legal domain. There is a long-recognised need for tools that enable users to browse, visualise, search, and manipulate arguments and argument structures. There is, however, a lack of widely accessible tools. In this article we describe the technology behind MARGOT, the first online argumentation mining system designed to reach out to the wider community of potential users of these new technologies. We evaluate its performance and discuss its possible application in the analysis of content from various domains. ©
Influence of Caffeine and Other Inotropic Interventions on the Onset of Unloaded Shortening Velocity in Mammalian Heart Muscle: Time Course of Activation

The onset of maximum unloaded shortening velocity was measured in cat papillary muscles by analyzing velocity with respect to time and length after zero load clamps imposed at different times. Unloaded shortening velocity rose rapidly to a constant level by 20% of the time to peak force under all conditions studied except with application of 10 mM caffeine, which markedly slowed its onset. Load-clamping experiments showed that the force-velocity-length interrelationship which characterizes shortening remained constant throughout most of shortening except with caffeine, which delayed the onset of steady state. It is suggested that the time course of the force-velocity-length interrelationship usefully describes velocity active state, the onset of which can be measured independently of force generation at zero load. In afterloaded contractions, manifestation of velocity active state may be delayed by the slower time course of force generation which precedes shortening. It is concluded that velocity active state normally rises rapidly to a constant level which describes the contractile state. Caffeine slows the onset of velocity active state, and valid time-independent force-peak velocity curves cannot be obtained in the presence of this drug.
Pursuing Sustainability with the Balanced Scorecard: Between Shareholder Value and Multiple Goal Optimisation

A rising awareness about the limitations of measuring organisational success merely with financial metrics has motivated researchers and practitioners to call for more holistic performance management and measurement systems. The balanced scorecard (BSC) as proposed by Kaplan and Norton is maybe the most popular framework which aims at a balance between multiple performance dimensions and objectives. Moreover, the increasing strategic importance of environmental and social aspects have led to the suggestion of a so called sustainability balanced scorecard (SBSC), which promises the consideration of even further performance dimensions. More specific, the SBSC aims at balancing financial objectives with environmental and social objectives. However, the SBSC approaches proposed strongly differ in the way they deal with managing multiple objectives. Against this background, we conduct a systematic review of the research field dealing with the SBSC in order to advance the knowledge on managing multiple corporate objectives. As part of our results, we first give a brief description of the research field using bibliographical analysis. Second, we derive a typology of generic SBSC architectures showing that the architecture is contingent on the value system the organisation chooses to operate in (profit driven, care driven, systemic driven) and the corporate sustainability strategy opted for (defence, accommodation, proaction). We further show that the architectures can generally be applied by various types of organisations (public listed, large private, and small and medium-sized companies), but that some combinations are more likely than others. Implications for management and research are also derived.
ADAR1 Interacts with PKR during Human Immunodeficiency Virus Infection of Lymphocytes and Contributes to Viral Replication

ABSTRACT The interferon-induced protein kinase RNA activated (PKR) is activated after virus infection. This activation is transient during the human immunodeficiency virus type 1 (HIV-1) infection of lymphocytes, and the protein is not activated at the peak of infection. We observed that interferon-induced adenosine deaminase acting on RNA 1-p150 (ADAR1-p150) and ADAR1-p110 expression increases while the virus replicates actively. Furthermore, both forms of ADAR1 show enhanced interactions with PKR at the peak of HIV infection, suggesting a role for this protein in the regulation of PKR activation. We observed that ADAR1-p150, as previously shown for the TAR RNA binding protein (TRBP), reverses the PKR inhibition of HIV expression and production in HEK 293T cells. This activity requires the Z-DNA binding motif and the three double-stranded RNA binding domains but not the catalytic domain. In astrocytic cells, ADAR1-p150 increased HIV expression and production to an extent similar to that of TRBP. Small interfering RNAs against ADAR1-p150 moderately decreased HIV production. These results indicate that two interferon-induced proteins, ADAR1 and PKR, have antagonistic functions on HIV production. They suggest that ADAR1 and TRBP belong to a multiprotein complex that inhibits PKR during the HIV infection of lymphocytes.
An Analysis of Trimming in Digital Social Networks

The study of network sizes in digital social networks is a research question of significant interest. Here, we explore the phenomenon of trimming, which is the decrease in the size of one’s network, and analyze if the rules of social exchange theory – namely, status consistency and reciprocity- can affect trimming. To this end, we use a Hidden Markov Model to investigate the relationship between the frequency of interaction and one’s network size, in which we are able to control for the current size of one’s digital social network. We find that there are significant patterns in sharing tendencies in digital social networks. One is that users who do not share enough are the group that is most likely to be trimmed from a network. Another is that users prefer to have moderate sized networks, i.e. networks with 500 – 1000 friends and prefer friends with moderate sharing tendencies (sharing approximately once a week). We also find that one’s sharing preferences over time tend to align with moderate sharing.
Metaphors and Categories

Despite the obvious affinity between the study of metaphor and the study of categorization, the link between these two fields of research has received little attention in cognitive psychology or in other disciplines. The purpose of the present study is precisely to establish and develop that link between those two research fields. After outlining the main recent developments in the modern study of categorization, focusing on the introduction of ad hoc categories, six major observations made in recent studies of metaphor comprehension (concerning, for example, the distinction between metaphors and non-metaphors, the asymmetry of metaphors, interpretation preference in metaphors, and the aptness of metaphors) are introduced. The main argument holds that these observations can be accounted for in a parsimonious and coherent way by assuming that metaphor comprehension is, in fact, a process of (ad hoc) category formation. The final section relates this proposal to alternative theories.
The Hsp60-(p.V98I) Mutation Associated with Hereditary Spastic Paraplegia SPG13 Compromises Chaperonin Function Both in Vitro and in Vivo*

We have previously reported the association of a mutation (c.292G > A/p.V98I) in the human HSPD1 gene that encodes the mitochondrial Hsp60 chaperonin with a dominantly inherited form of hereditary spastic paraplegia. Here, we show that the purified Hsp60-(p.V98I) chaperonin displays decreased ATPase activity and exhibits a strongly reduced capacity to promote folding of denatured malate dehydrogenase in vitro. To test its in vivo functions, we engineered a bacterial model system that lacks the endogenous chaperonin genes and harbors two plasmids carrying differentially inducible operons with human Hsp10 and wild-type Hsp60 or Hsp10 and Hsp60-(p.V98I), respectively. Ten hours after shutdown of the wild-type chaperonin operon and induction of the Hsp60-(p.V98I)/Hsp10 mutant operon, bacterial cell growth was strongly inhibited. No globally increased protein aggregation was observed, and microarray analyses showed that a number of genes involved in metabolic pathways, some of which are essential for robust aerobic growth, were strongly up-regulated in Hsp60-(p.V98I)-expressing bacteria, suggesting that the growth arrest was caused by defective folding of some essential proteins. Co-expression of Hsp60-(p.V98I) and wild-type Hsp60 exerted a dominant negative effect only when the chaperonin genes were expressed at relatively low levels. Based on our in vivo and in vitro data, we propose that the major effect of heterozygosity for the Hsp60-(p.V98I) mutation is a moderately decreased activity of chaperonin complexes composed of mixed wild-type and Hsp60-(p.V98I) mutant subunits.
An emancipatory research on CBR and the barriers faced by persons with disabilities

Abstract Purpose: The aim of this research was to understand the barriers faced by persons with disabilities in their daily lives and the role of CBR projects in overcoming them. Method: A group of persons with disabilities involved in CBR activities was identified and trained in participatory research methodologies. Research was carried out, with support from a scientific advisory group, through sharing of life stories in residential meetings focusing on specific themes. These meetings were attended by 368 persons with disabilities. Results: The barriers identified ranged from isolation, neglect, abuse and violence to lack of access to social, health, education and livelihood opportunities. People faced their first barriers in their own families. Families also played an important role in overcoming some barriers at the individual level. CBR projects assisted people in overcoming barriers mainly by providing information, by facilitating access to existing support and by helping persons in communities to take collective action against the barriers. The research also stimulated DPOs and CBR projects to identify some gaps in tackling the barriers and to start action to overcome them. Conclusions: CBR projects can play a role in overcoming some barriers faced by persons with disabilities. Emancipatory research yields rich data, facilitates ownership and possibly future sustainability. Implications for Rehabilitation Community-based rehabilitation (CBR) programmes can promote mainstreaming and helping in overcoming some barriers faced by persons with disabilities in the communities. CBR programmes can facilitate collective action by persons with disabilities in overcoming barriers to inclusion and participation. Participatory research approaches such as emancipatory research can play a role in understanding disability issues and at the same time, help CBR programmes to identify gaps and strengthen activities.
Cloning, Expression, and Purification of the K5 Capsular Polysaccharide Lyase (KflA) from Coliphage K5A: Evidence for Two Distinct K5 Lyase Enzymes

ABSTRACT The Escherichia coli K5 capsular polysaccharide [-4)-βGlcA-(1,4)-αGlcNAc-(1-] is a receptor for the capsule-specific bacteriophage K5A. Associated with the structure of bacteriophage K5A is a polysaccharide lyase which degrades the K5 capsule to expose the underlying bacterial cell surface. The bacteriophage K5A lyase gene (kflA) was cloned and sequenced. The kflA gene encodes a polypeptide with a predicted molecular mass of 66.9 kDa and which exhibits amino acid homology with ElmA, a K5 polysaccharide lyase encoded on the chromosome of E. coli SEBR 3282. There was only limited nucleotide homology between the kflA and elmA genes, suggesting that these two genes are distinct and either have been derived from separate progenitors or have diverged from a common progenitor for a considerable length of time. Southern blot analysis revealed that kflA was not present on the chromosome of theE. coli strains examined. In contrast, elmA was present in a subset of E. coli strains. Homology was observed between DNA flanking the kflA gene of bacteriophage K5A and DNA flanking a small open reading frame (ORFL) located 5′ of the endosialidase gene of the E. coli K1 capsule-specific bacteriophage K1E. The DNA homology between these noncoding sequences indicated that bacteriophages K5A and K1E were related. The deduced polypeptide sequence of ORFLin bacteriophage K1E exhibited homology to the N terminus of KflA from bacteriophage K5A, suggesting that ORFL is a truncated remnant of KflA. The presence of this truncated kflA gene implies that bacteriophage K1E has evolved from bacteriophage K5A by acquisition of the endosialidase gene and subsequent loss of functionalkflA. A (His)6-KflA fusion protein was overexpressed in E. coli and purified to homogeneity with a yield of 4.8 mg per liter of bacterial culture. The recombinant enzyme was active over a broad pH range and NaCl concentration and was capable of degrading K5 polysaccharide into a low-molecular-weight product.
Select the Valid and Relevant Moments: A One-Step Procedure for GMM with Many Moments

This paper considers the selection of valid and relevant moments for the generalized method of moments (GMM) estimation. For applications with many candidate moments, our asymptotic analysis ccommodates a diverging number of moments as the sample size increases. The proposed procedure achieves three objectives in one-step: (i) the valid and relevant moments are selected simultaneously rather than sequentially; (ii) all desired moments are selected together instead of in a stepwise manner; (iii) the parameter of interest is automatically estimated with all selected moments as opposed to a post-selection estimation. The new moment selection method is achieved via an information-based adaptive GMM shrinkage estimation, where an appropriate penalty is attached to the standard GMM criterion to link moment selection to shrinkage estimation. The penalty is designed to signal both moment validity and relevance for consistent moment selection and efficient estimation. The asymptotic analysis allows for non -smooth sample moments and weakly dependent observations, making it generally applicable. For practical implementation, this one-step procedure is computationally attractive.
How do humans process and recognize speech?

Until the performance of automatic speech recognition (ASR) hardware surpasses human performance in accuracy and robustness, we stand to gain by understanding the basic principles behind human speech recognition (HSR). This problem was studied exhaustively at Bell Labs between the years of 1918 and 1950 by Harvey Fletcher and his colleagues. The motivation for these studies was to quantify the quality of speech sounds in the telephone plant to both improve speech intelligibility and preference. To do this he and his group studied the effects of filtering and noise on speech recognition accuracy for nonsense consonant-vowel-consonant (CVC) syllables, words, and sentences. Fletcher used the term "articulation" as the probability of correct recognition for nonsense sounds, and "intelligibility" as the probability of correction recognition for words (sounds having meaning). In 1919, Fletcher found a way to transform articulation data for filtered speech into an additive density function D(f) and found a formula that accurately predicts the average articulation. The area under D(S) is called the "articulation index. " Fletcher then went on to find relationships between the recognition errors for the nonsense speech sounds, words, and sentences. This work has recently been reviewed and partially replicated by Boothroyd and by Bronkhorst, et al. (1980). Taken as a whole, these studies tell us a great deal about how humans process and recognize speech sounds. >
COMPLETE CONTROLLABILITY OF SEMILINEAR STOCHASTIC SYSTEMS WITH DELAY IN BOTH STATE AND CONTROL

This paper deals with the complete controllability of semilinear stochastic systems with delay in both state and control under the assumption that the corresponding linear system is completely controllable. The control function for this system is suitably constructed by using the controllability operator. With this control function, the sufficient conditions for the complete controllability of the proposed problem in finite dimensional are established. The results are obtained by using Banach fixed point theorem. Finally, one example is provided to illustrate the application of the obtained results.
Topology simplification strategy for connected multi-agent systems

Some applications of multi-agent systems require the whole group of agents to be spread into the environment from initially compact connection configurations; as a result, the group connection topology tends to be sparser as the agents move. On the other hand, preserving group connectedness is often regarded as a fundamental necessity for networked operations. To take requirements of both dispersion and connectedness into consideration, a distributed algorithm of 'cutting off' redundant edges based on local information is developed in this paper. With this algorithm, a simplified connection graph is extracted from the actual communication topology, which keeps the connectedness of the actual topology with less but robust communication links. The performance of the algorithm is analysed and simulated. Finally, we apply this distributed algorithm in solving a connected dispersion problem which spreads out the agents while simultaneously maintaining their connectedness; and its effectiveness is shown by simulations.
SVM-based road verification with partly non-representative training data

In this paper we present a SVM-based method for automatic quality control of a road database in urban areas. The road verification is carried out by comparing the database objects to high-resolution aerial imagery. The method is trimmed to produce reliable results even if the training data selection is partly non-epresentative. A reliability metric is assigned to the SVM decision that is based on the distance of a test object to the training data. This metric can be applied to any SVM-based classification task. Our experiments show that the classifier is very reliable in only accepting road objects that are actually correct.
Site-specific integration of a transgene mediated by a hybrid adenovirus/adeno-associated virus vector using the Cre/loxP-expression-switching system.

As vectors, adenoviruses (Ads) have many attractive advantages for in vivo gene therapy. However, Ads do not usually integrate into the host genome and gene expression is, thus, transient. Adeno-associated virus (AAV) integrates into a specific locus (AAVS1) on the human host's chromosome 19, while conventional recombinant AAV (rAAV) vectors do not possess this property because such vectors lack the rep gene. AAV vectors carrying the rep gene do not have enough space for insertion of a transgene. We have constructed a hybrid adenovirus/adeno-associated virus (Ad/AAV) vector which has the advantages of both Ads and AAVs. Given that the rep gene products inhibit propagation of Ads, we used the Cre/loxP-expression-switching system to regulate the expression of the rep gene. The Ad/AAV vector easily propagates, can efficiently infect a broad range of cell types, and can integrate into a specific locus on host chromosomes.
Performance of buffered banyan networks under nonuniform traffic patterns

An analytical method of evaluating the performance of the buffered banyan packet-switching network under nonuniform traffic patterns is presented. It is shown that nonuniform traffic can have a detrimental effect on the performance of the network. The analytical model is extended to evaluate the performance of multibuffer and parallel banyan networks. These modified networks are shown to have better throughput capacity and delay performance than the single-buffer banyan network. >