Miracle-dz/UniFAR-FTUs huggingface dataset:
The grade of pancreatic ductal carcinoma is an independent prognostic factor and is superior to the immunohistochemical assessment of proliferation

Tumour grade is one of the prognostic factors in pancreatic ductal adenocarcinoma, but its value is controversial. In this study, the predictive value and the reproducibility of the WHO grading system were reconsidered and the possibility of supplementing it with the immunohistochemically assessed proliferative activity was investigated. Seventy resected ductal adenocarcinomas of the head of the pancreas were evaluated. A total of 60 HPF fields on two to four sections per tumour were screened for glandular differentiation, mucin production, mitosis, and nuclear atypia by two observers with different degrees of experience. Each criterion was scored and the grade was calculated from the mean value of all single scores. Corresponding slides were immunohistochemically stained with the proliferation marker Ki‐S5. The percentage of positive nuclei was assessed and a proliferation index (PI) assigned (<10%=1; 10–50%=2; >50%=3). Multivariate analysis (Cox regression) identified grade and R stage as the most significant factors for predicting survival. The PI determined on the basis of Ki‐S5 staining did not prove to be an independent prognostic factor. In 30 of 70 carcinomas, it correlated with the tumour grade. Within a given tumour grade, the cases with the least favourable prognosis could be distinguished on the basis of their PI. The inter‐observer variability was considerable, with the main differences occurring in the group of G1 tumours. According to the refined WHO criteria, the histopathological grade of pancreatic ductal carcinoma is an important independent prognostic factor, but reproducibility depends on the expertise of the observer. Criteria that relate to cellular and structural differentiation seem to be more predictive than those related to proliferation. Copyright © 2000 John Wiley & Sons, Ltd.
The RNA component of human telomerase

Eukaryotic chromosomes are capped with repetitive telomere sequences that protect the ends from damage and rearrangements. Telomere repeats are synthesized by telomerase, a ribonucleic acid (RNA)-protein complex. Here, the cloning of the RNA component of human telomerase, termed hTR, is described. The template region of hTR encompasses 11 nucleotides (5'-CUAACCCUAAC) complementary to the human telomere sequence (TTAGGG)n. Germline tissues and tumor cell lines expressed more hTR than normal somatic cells and tissues, which have no detectable telomerase activity. Human cell lines that expressed hTR mutated in the template region generated the predicted mutant telomerase activity. HeLa cells transfected with an antisense hTR lost telomeric DNA and began to die after 23 to 26 doublings. Thus, human telomerase is a critical enzyme for the long-term proliferation of immortal tumor cells.
The creative environment scales: Work environment inventory

Abstract: The Creative Environment Scales Work Environment Inventory (WEI) is a new paper‐and‐pencil instrument designed to assess stimulants and obstacles to creativity in the work environment. Unlike many instruments that are designed as comprehensive descriptions of the work environment, the WEI focuses on those factors in the work environment that are most likely to influence the expression and development of creative ideas. Designed to be used at any level within any function of an organization, the WEI is intended as an organizational development instrument to improve the climate for creativity. Conceptually grounded in previous empirical and theoretical work on creativity and innovation, the WEI has been administered to 645 respondents drawn from five different groups. Factor analyses, scale reliabilities (internal consistencies), and between/within scale correlations indicate a high degree of integrity in the WEI scales. Furthermore, test‐retest reliability is high. Preliminary validity analyses i.
Door-to-balloon time in primary percutaneous coronary intervention: is the 90-minute gold standard an unreachable chimera?

Over the past decade, primary percutaneous coronary intervention (PCI) has emerged as an effective treatment strategy for acute ST-segment–elevation myocardial infarction (STEMI). Compared with thrombolytic therapy, the benefits of primary PCI include a reduction in the frequency of total stroke and hemorrhagic stroke, a reduction in the frequency of reinfarction, and an increase in the frequency of infarct-related artery patency, resulting in improved in-hospital and long-term survival.1 In addition, the availability of primary PCI provides a valid alternative for patients who have contraindications to thrombolytic therapy. Article p 1079 These observations have led many institutions to select primary PCI as the preferred treatment strategy for patients with acute STEMI. In addition, after the publication of several reports on the safety and efficacy of primary PCI in centers without cardiac surgery on site,2,3 several state regulatory agencies have changed local regulations by allowing primary PCI for acute STEMI in centers without cardiac surgery on site. Thus, it is likely that the next decade will be characterized by further expansion of primary PCI for acute STEMI in hospitals with cardiac catheterization laboratories. As previously shown for thrombolytic therapy, time to treatment also plays a key role in survival with primary PCI. In the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb) substudy,4 the lowest 30-day mortality rate was observed in patients undergoing primary PCI within 60 minutes from presentation to the emergency room, whereas the highest mortality rate was observed in patients undergoing PCI >90 minutes from presentation (1.0% versus 6.4%). Similar compelling data were reported in an analysis of data from the National Registry of Acute Myocardial Infarction (NRMI). In that analysis, which included 27 080 patients, the lowest mortality rate again was observed in patients undergoing PCI within 60 minutes from presentation, …
RMSProp and equilibrated adaptive learning rates for non-convex optimization

Parameter-specific adaptive learning rate methods are computationally efficient ways to reduce the ill-conditioning problems encountered when training large deep networks. Following recent work that strongly suggests that most of the critical points encountered when training such networks are saddle points, we find how considering the presence of negative eigenvalues of the Hessian could help us design better suited adaptive learning rate schemes, i.e., diagonal preconditioners. We show that the optimal preconditioner is based on taking the absolute value of the Hessian's eigenvalues, which is not what Newton and classical preconditioners like Jacobi's do. In this paper, we propose a novel adaptive learning rate scheme based on the equilibration preconditioner and show that RMSProp approximates it, which may explain some of its success in the presence of saddle points. Whereas RMSProp is a biased estimator of the equilibration preconditioner, the proposed stochastic estimator, ESGD, is unbiased and only adds a small percentage to computing time. We find that both schemes yield very similar step directions but that ESGD sometimes surpasses RMSProp in terms of convergence speed, always clearly improving over plain stochastic gradient descent.
Widespread Genomic Incompatibilities in Caenorhabditis elegans

In the Bateson-Dobzhansky-Muller (BDM) model of speciation, incompatibilities emerge from the deleterious interactions between alleles that are neutral or advantageous in the original genetic backgrounds, i.e., negative epistatic effects. Within species such interactions are responsible for outbreeding depression and F2 (hybrid) breakdown. We sought to identify BDM incompatibilities in the nematode Caenorhabditis elegans by looking for genomic regions that disrupt egg laying; a complex, highly regulated, and coordinated phenotype. Investigation of introgression lines and recombinant inbred lines derived from the isolates CB4856 and N2 uncovered multiple incompatibility quantitative trait loci (QTL). These QTL produce a synthetic egg-laying defective phenotype not seen in CB4856 and N2 nor in other wild isolates. For two of the QTL regions, results are inconsistent with a model of pairwise interaction between two loci, suggesting that the incompatibilities are a consequence of complex interactions between multiple loci. Analysis of additional life history traits indicates that the QTL regions identified in these screens are associated with effects on other traits such as lifespan and reproduction, suggesting that the incompatibilities are likely to be deleterious. Taken together, these results indicate that numerous BDM incompatibilities that could contribute to reproductive isolation can be detected and mapped within C. elegans.
Optimal Incentive Contracts in the Presence of Career Concerns: Theory and Evidence

This paper studies optimal incentive contracts when workers have career concerns--concerns about the effects of current performance on future compensation. We show that the optimal compensation contract optimizes total incentives: the combination of the implicit incentives from career concerns and the explicit incentives from the compensation contract. Thus the explicit incentives from the optimal compensation contract should be strongest for workers close to retirement because career concerns are weakest for these workers. We find empirical support for this prediction in the relation between chief executive compensation and stock market performance.
Presentation and Representation in Design Problem Solving.

Abstract : Two experimental studies of design problem solving are presented. Eighty-one subjects worked on one of two design problems that were isomorphic in structure: a schedule for stages in a manufacturing process or a layout for a business office. In Experiment 1, a difference between problem isomorphs is obtained: the 'spatial' office layout problem obtains better performance and shorter solution times than the 'temporal' scheduling problem. In Experiment 2, this difference attenuates when subjects are provided with a graphic representation in both isomorph conditions. The availability of a graphic representation is discussed as an aid for procedural design. (Author)
Antecedents of employee performance: an empirical investigation in India

Purpose – The purpose of this paper is to examine the relationship between psychological climate, and transformational leadership, with employee performance. The paper builds on relevant research in this area, and extends such research to the Indian context.Design/methodology/approach – Data were gathered from 357 participants in Indian organizations, who responded to questions regarding their work environment and perceived supervisory support. The respondents' demographic data were treated as control variables.Findings – As predicted, it was found that organizational psychological climate, and transformational leadership, predicted job satisfaction. Job satisfaction, in turn, predicted employee performance, a composite measure of in‐role and extra‐role performance.Research limitations/implications – All data were collected from the participants at one point of time – as such, causality cannot be inferred, and the results may be subject to common method bias.Practical implications – From a practical persp.
Fimbria-like hemagglutinin of Escherichia coli O75 strains

Fifteen strains of Escherichia coli O75 from human feces and patients with urinary tract infections were analyzed for their hemagglutinative properties, production of hemolysin and colicin, and plasmid contents. Fourteen strains produced type-1 fimbriae in broth culture. Nine of the strains agglutinated human P1 and p erythrocytes, i.e., possessed an X adhesin (X hemagglutinin). All but one of the X+ strains agglutinated human but not sheep or rabbit erythrocytes. Of the 15 strains, 4 had P fimbriae; one strain had both X hemagglutinin and P fimbriae. A coli-like structure was found by electron microscopy on the surface of the X+ strains. This structure was purified from two strains and characterized chemically and serologically. It was a protein consisting of subunits with an apparent molecular weight of 16,000. The amounts of hydrophobic amino acids in proteins purified from strains IH11033 and IH11128 were 35 and 39%, respectively. The amino acid content of the proteins was quite similar; only glutamine-glutamate and tyrosine contents were different. The radiolabeled protein bound to human erythrocytes, but it differed morphologically from typical E. coli fimbriae. Several methods showed the hemagglutinin, termed O75-X, to be serologically related in all the O75 X+ strains. The eight X+ O75:K5:H- strains had type-1 fimbriae and an identical outer membrane protein pattern, lacked P fimbriae and hemolytic activity, and are proposed to represent a clonal group.
Hidden Implementation Dependencies in High Assurance and Critical Computing Systems

Critical and catastrophic failures in high assurance and critical computing systems can arise from unfounded assumptions of independence between system components, requirements, and constraints (work product sections), which can stem from misunderstandings and miscommunication between system engineers, managers, and operators and from inadequate or incomplete traceability between system work products. In this article, we propose a formal framework for the effective implementation of traceability between work product sections along with a technique for discovering potential causes of critical failures in high assurance and critical computing system models. We introduce a new abstraction of interrelated work product sections called implementation meta-work product and describe how our technique finds these meta-work products. We also demonstrate how this technique can be used to help analysts discover potential causes of safety-related errors in high assurance and critical computing systems by applying it to one case study of a known critical error and to one case study where we anticipate potential safety hazards
Structural basis for antibody recognition of the NANP repeats in Plasmodium falciparum circumsporozoite protein

Significance The Plasmodium falciparum circumsporozoite protein (CSP) has been studied for decades as a potential immunogen, but little structural information is available on how antibodies recognize the immunodominant NANP repeats within CSP. The most advanced vaccine candidate is RTS,S, which includes multiple NANP repeats. Here, we analyzed two functional antibodies from an RTS,S trial and determined the number of repeats that interact with the antibody Fab fragments using isothermal titration calorimetry and X-ray crystallography. Using negative-stain electron microscopy, we also established how the antibody binds to the NANP repeat region in a recombinant CSP construct. The structural features outlined here provide a rationale for structure-based immunogen design to improve upon the efficacy of the current RTS,S vaccine. Acquired resistance against antimalarial drugs has further increased the need for an effective malaria vaccine. The current leading candidate, RTS,S, is a recombinant circumsporozoite protein (CSP)-based vaccine against Plasmodium falciparum that contains 19 NANP repeats followed by a thrombospondin repeat domain. Although RTS,S has undergone extensive clinical testing and has progressed through phase III clinical trials, continued efforts are underway to enhance its efficacy and duration of protection. Here, we determined that two monoclonal antibodies (mAbs 311 and 317), isolated from a recent controlled human malaria infection trial exploring a delayed fractional dose, inhibit parasite development in vivo by at least 97%. Crystal structures of antibody fragments (Fabs) 311 and 317 with an (NPNA)3 peptide illustrate their different binding modes. Notwithstanding, one and three of the three NPNA repeats adopt similar well-defined type I β-turns with Fab311 and Fab317, respectively. Furthermore, to explore antibody binding in the context of P. falciparum CSP, we used negative-stain electron microscopy on a recombinant shortened CSP (rsCSP) construct saturated with Fabs. Both complexes display a compact rsCSP with multiple Fabs bound, with the rsCSP–Fab311 complex forming a highly organized helical structure. Together, these structural insights may aid in the design of a next-generation malaria vaccine.
Moving beyond developmental paradigms: A case study and analysis of a TfD workshop in Bangladesh

The authors give a personal account of a one week Theatre for Development Workshop held in Manmathapur in Northern Bangladesh, sponsored by the British Council. The practice of short, workshops facilitated by urban ‘experts’ in impoverished rural areas is heavily critiqued. This opens into a broader critique of the manipulative and paternalistic attitudes which often undermine the effectiveness of post-colonial development communications, due to global power imbalances. Modesty is urged for the strategizing and practice of such workshops through a return to the participatory principles of Paulo Freire. The paper describes the advantages of ‘Barter Theatre’ as a methodology which attempts to ensure equality in the exchange of skills and ideas between marginalized, host communities and visiting facilitators. The potential of such intercultural ‘bartering’ is linked both to the injustices caused by, and potential resistance to, globalized communications.
Detecting Community Structure by Using a Constrained Label Propagation Algorithm

Community structure is considered one of the most interesting features in complex networks. Many real-world complex systems exhibit community structure, where individuals with similar properties form a community. The identification of communities in a network is important for understanding the structure of said network, in a specific perspective. Thus, community detection in complex networks gained immense interest over the last decade. A lot of community detection methods were proposed, and one of them is the label propagation algorithm (LPA). The simplicity and time efficiency of the LPA make it a popular community detection method. However, the LPA suffers from instability detection due to randomness that is induced in the algorithm. The focus of this paper is to improve the stability and accuracy of the LPA, while retaining its simplicity. Our proposed algorithm will first detect the main communities in a network by using the number of mutual neighbouring nodes. Subsequently, nodes are added into communities by using a constrained LPA. Those constraints are then gradually relaxed until all nodes are assigned into groups. In order to refine the quality of the detected communities, nodes in communities can be switched to another community or removed from their current communities at various stages of the algorithm. We evaluated our algorithm on three types of benchmark networks, namely the Lancichinetti-Fortunato-Radicchi (LFR), Relaxed Caveman (RC) and Girvan-Newman (GN) benchmarks. We also apply the present algorithm to some real-world networks of various sizes. The current results show some promising potential, of the proposed algorithm, in terms of detecting communities accurately. Furthermore, our constrained LPA has a robustness and stability that are significantly better than the simple LPA as it is able to yield deterministic results.
Staphylococcus aureus-Induced Plasmacytoid Dendritic Cell Activation Is Based on an IgG-Mediated Memory Response1

Type I IFNs represent a major antimicrobial defense mechanism due to their property of enhancing immune responses by priming both innate and adaptive immune cells. Plasmacytoid dendritic cells (pDC) are the major source of type I IFN in the human body and represent innate immune cells involved in first-line defense against invading pathogens. Although pDC activation has been extensively studied upon stimulation with synthetic TLR ligands, viruses, and intracellular bacteria, there is only scarce information on extracellular bacteria. In this study we show that the triggering of human pDC-derived IFN-α secretion by Staphylococcus aureus is independent of TLR2 and specific for coagulase-positive staphylococci. Specificity of the pDC response to S. aureus is independent of the bacterial virulence factors protein A and α-toxin but is mediated by Ag-specific IgG and CD32. S. aureus-induced pDC activation can be blocked by inhibitory DNA oligonucleotides and chloroquine, suggesting that engagement of TLR7/9 by bacterial nucleic acids after CD32-mediated uptake of these compounds may play a central role in this process. Altogether, we propose that in marked contrast to nonselective TLR2-dependent activation of most innate immune cells, pDC activation by S. aureus represents an Ag-specific memory response since it requires the presence of class-switched immunoglobulins.
Mining software repositories using topic models

Software repositories, such as source code, email archives, and bug databases, contain unstructured and unlabeled text that is difficult to analyze with traditional techniques. We propose the use of statistical topic models to automatically discover structure in these textual repositories. This discovered structure has the potential to be used in software engineering tasks, such as bug prediction and traceability link recovery. Our research goal is to address the challenges of applying topic models to software repositories.
Disorders of Emotions: Clarification, Elaboration, and Future Directions

It is a rare privilege indeed to have 13 of the leading authorities in the world attend carefully to one's work. Among this illustrious group, I would single out Hans Eysenck, who has influenced me deeply since my student days, both clinically and scientifically. Joining Eysenck and my other distinguished colleagues in the world of ideas is a stimulating experience indeed. Before responding to substantive issues, I note that it is not surprising that several of the commentators found the model outlined in my article unclear in places. The necessity of condensing a description of ideas and hypotheses into these
Denial of Service / Distributed Denial of Service MANAGING DoS ATTACKS

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Stable Computation of the CS Decomposition: Simultaneous Bidiagonalization

Since its discovery in 1977, the CS decomposition (CSD) has resisted computation, even though it is a sibling of the well-understood eigenvalue and singular value decompositions. Several algorithms have been developed for the reduced 2-by-1 form of the decomposition, but none have been extended to the complete 2-by-2 form of the decomposition in Stewart's original paper. In this article, we present an algorithm for simultaneously bidiagonalizing the four blocks of a unitary matrix partitioned into a 2-by-2 block structure. This serves as the first, direct phase of a two-stage algorithm for the CSD, much as Golub-Kahan-Reinsch bidiagonalization serves as the first stage in computing the singular value decomposition. Backward stability is proved.