Miracle-dz/UniFAR-FTUs huggingface dataset:
Why do clinical trials fail? The problem of measurement error in clinical trials: time to test new paradigms?

A recent review 1 of the Food and Drug Administration data sets including 45 trials found that 36% of these studies failed to show superiority of a standard antidepressant over placebo. (In the case of new antidepressants, the failure rate was 52%). In addition, it has become increasingly difficult for trials with known effective drugs to show signal detection with similar numbers of patients as trials conducted in the 1960s, 1970s, or early 1980s. This increasingly high rate of failed central nervous system trials, as well as the smaller effect sizes observed in positive studies, continues to receive much attention. We believe that poor reliability of measurement, poor interview quality (which extends to evaluation and diagnosis), and rater bias are largely to blame for this problem and that this problem can be remedied. Although clinician-administered rating scales form the building blocks upon which the entire clinical trial rests, only recently have factors associated with the clinical assessment process come under closer scrutiny as a possible source of trial failure and poor signal detection. As Fleiss has said, ‘‘The most elegant design of a clinical study will not overcome the damage caused by unreliable or imprecise measurement. ’’ A variety of studies illustrate how factors associated with clinician ratings (ie, interrater reliability, interview quality, and rater bias) can significantly impact signal detection and study outcome. In what follows, we consider these problems, which have been the object of recent research. Questions around diagnostic validity and/or shifts in patient populations remain to be evaluated.
2-[18f]-2-deoxy-d-glucose (fdg) uptake in human tumor cells is related to the expression of glut-1 and hexokinase ii

Background: The uptake of 2-[18F]-2-deoxy-D-glucose (18F-FDG) is widely used as a marker of increased glucose metabolism to monitor progression of cancers with positron emission tomography (PET). Many tumors have been shown to overexpress facilitated glucose transporters, especially GLUT-1 and a glycolytic enzyme, hexokinase II. Purpose: To define whether a quantitative relationship exists between the expression levels of GLUT-1 and hexokinase II, and 18F-FDG uptake in human cancer xenografts. Material and Methods: We determined the expression levels of both GLUT-1 and hexokinase II in normal cells and in five different human cancer cell lines (AGS, A431, A549, Colo 320 HSR, and HepG2) using Western blot analysis. In vitro assays of 18F-FDG uptake in cultures were performed, and subsequently representative cell lines were inoculated onto the flanks of severe combined immunodeficient (SCID) mice. To establish an orthotopic model of human hepatocellular carcinoma (HCC), cells were injected into the intraportal vein of SCID mice. 18F-FDG uptake in vivo was assessed by subjecting mice to PET imaging. Results: All cell lines were shown to express higher amounts of GLUT-1 and hexokinase II compared with fibroblast controls. Our results from in vitro 18F-FDG uptake assays also correlated with the Western blot results. All xenografts gave highly positive results at microPET imaging, and a strong correlation (R 2=0.88, P<0.001) was found between the maximum standardized uptake values (SUVmax) and the expression of GLUT-1 proteins. Conclusion: Our data indicate that the expression levels of GLUT-1 and hexokinase II as well as in vitro assays of FDG uptake serve as good screening tests to evaluate the feasibility of cell lines to be further developed into xenograft cancer models for small-animal PET imaging.
Scalable Statistical Relational Learning for NLP

: Statistical Relational Learning (SRL) is an interdisciplinary research area that combines first­order logic and machine learning methods for probabilistic inference. Although many Natural Language Processing (NLP) tasks (including text classification, semantic parsing, information extraction, coreference resolution, and sentiment analysis) can be formulated as inference in a first­order logic, most probabilistic first­order logics are not efficient enough to be used for large­scale versions of these tasks. In this tutorial, we provide a gentle introduction to the theoretical foundation of probabilistic logics, as well as their applications in NLP. We describe recent advances in designing scalable probabilistic logics, with a special focus on ProPPR. Finally, we provide a hands­on demo about scalable probabilistic logic programming for solving practical NLP problems
PSM Peptides of Staphylococcus aureus Activate the p38–CREB Pathway in Dendritic Cells, Thereby Modulating Cytokine Production and T Cell Priming

The challenging human pathogen Staphylococcus aureus has highly efficient immune evasion strategies for causing a wide range of diseases, from skin and soft tissue to life-threatening infections. Phenol-soluble modulin (PSM) peptides are major pathogenicity factors of community-associated methicillin-resistant S. aureus strains. In previous work, we demonstrated that PSMs in combination with TLR2 ligand from S. aureus induce tolerogenic dendritic cells (DCs) characterized by the production of high amounts of IL-10, but no proinflammatory cytokines. This in turn promotes the activation of regulatory T cells while impairing Th1 response; however, the signaling pathways modulated by PSMs remain elusive. In this study, we analyzed the effects of PSMs on signaling pathway modulation downstream of TLR2. TLR2 stimulation in combination with PSMα3 led to increased and prolonged phosphorylation of NF-κB, ERK, p38, and CREB in mouse bone marrow–derived DCs compared with single TLR2 activation. Furthermore, inhibition of p38 and downstream MSK1 prevented IL-10 production, which in turn reduced the capacity of DCs to activate regulatory T cells. Interestingly, the modulation of the signaling pathways by PSMs was independent of the known receptor for PSMs, as shown by experiments with DCs lacking the formyl peptide receptor 2. Instead, PSMs penetrate the cell membrane most likely by transient pore formation. Moreover, colocalization of PSMs and p38 was observed near the plasma membrane in the cytosol, indicating a direct interaction. Thus, PSMs from S. aureus directly modulate the signaling pathway p38–CREB in DCs, thereby impairing cytokine production and in consequence T cell priming to increase the tolerance toward the pathogen.
Riding the Waves of Investment Returns

It is common knowledge that economic activity follows cyclical processes of different length like the business cycle or seasonal patterns throughout a calendar year. These cyclical patterns are usually distorted by noise and singular events that influence financial markets over the short term. This paper shows how one can filter out the cyclical patterns of investment returns and use this information in order to create superior active investment returns. It is shown that the filtered data will be a good indication of return trends for the asset class considered. In the long run (that is an investment horizon of more than four years) the short term noise should be of negligible importance for the investment performance. This implies that a portfolio that dynamically allocates the portfolio weights according to the expected future filtered returns should be able to add value for long term investors. Here, a simple dynamic portfolio asset allocation process is developed based on the future returns as calculated from the filtered data. The performance of this model portfolio is compared to a passive benchmark portfolio with fixed portfolio weights and maximum Sharpe ratio for the sampling period as well as to an active portfolio that allocates the portfolio weights with a simple momentum approach. The results of our in sample as well as our out of the sample tests show that the model portfolio that relies only on medium to long term cyclical economic activity does outperform both the passive benchmark and the actively managed momentum portfolio in terms of absolute return and in terms of risk adjusted returns (Sharpe ratio). The outperformance is high enough (generally between 1.5% and 5% per annum) to persist even when transaction costs are considered in the model. Also, the Information Ratios of the Model Portfolios are generally in the region between 0.4 and 0.7 for the out of sample data which is an excellent value for a purely quantitative approach. Finally, the superior performance appears to be stable over investment horizons of more than four years.
Considering the Effects of Time on Leadership Development

As local governments across the United States adapt to economic shifts, workforce reshaping, and continued demand for services, training to confront these challenges has become more important. However, training resources are limited, investment in these programs is not always prioritized, and evaluating outcomes is difficult. This study analyzes data from a local government leadership development program to examine training impacts over time. It focuses on leadership skills and the ways in which individual’s self-assessments change over time. The findings indicate that although leadership training is an important factor in the development of both conceptual and interpersonal leadership skills, the long-term effects of training on these two types of skills vary significantly. Understanding the training effect decay associated with leadership skills development can help human resource managers and public organizations strategically plan, evaluate, and invest in these training activities to better prepare their workforce to meet future challenges.
Theoretical Models of Microvascular Oxygen Transport to Tissue

To improve understanding of microvascular O2 transport, theoretical modeling has been pursued for many years. The large number of studies in this area attests to the complexities (i.e., biochemical, structural, and hemodynamic) involved. This article focuses on theoretical studies from the last two decades and, in particular, on models of O2 transport to tissue by discrete microvessels. A brief discussion of intravascular O2 transport is first given, highlighting the physiological importance of intravascular resistance to blood‐tissue O2 transfer. This is followed by a description of the Krogh tissue cylinder model of O2 transport by a single capillary, which is shown to remain relevant in modified forms that relax many of the original biophysical assumptions. However, there are many geometric and hemodynamic complexities that require the consideration of microvascular arrays and networks. Multivessel models are discussed that have shown the physiological importance of heterogeneities in vessel spacing, O2 supply, red blood cell flow path, as well as interactions between capillaries and arterioles. These realistic models require sophisticated methods for solving the governing partial differential equations, and a range of solution techniques are described. Finally, the issue of experimental validation of microvascular O2 delivery models is discussed, and new directions in O2 transport modeling are outlined.
Effect of Regional Cellular Uncoupling in presence of LQTS2 in a 2D Cardiac Tissue

Ischemia in presence of drug induced long QT syndrome 2 (LQTS2) predisposes the tissue to Torsade de pointes (TdP). Reentrant arrhythmias occurring during phase 1B of ischemia have been primarily associated with areas of cellular uncoupling and hyperkalaemia. This study aims to investigate how a region of lowered gap junction conductance (GJC) in presence of LQTS2 can initiate a TdP. Here, a discrete grid of 250x100 cells interconnected using GJCs is taken representing a portion of the transmural wall with anisotropic conduction velocities. LQTS2 is introduced by reducing the potassium current (IKr) of all cells to 50%. An ischemic zone is located almost in the centre of the mid myocardium layer in the form of an elliptic inhomogeneity with varying percentage reduction of GJC compared to the surrounding. Results show that reduction of intercellular conductance in a midmyocardial island can cause a non-sustained reentrant arrhythmia to develop due to premature pacing beats. Addition of hyperkalaemic conditions in the ischemic zone has the effect of prolonging the arrhythmia.
Approximate Stochastic Stability with an Application to the Survival of Walrasian Conjectures in Cournot Oligopoly

This paper presents a general framework for analysing stochastic stability in models with evolution at two levels. Under certain conditions these two levels can be disentangled and studied separately. In such cases the limit distribution at one level can be used to approximate the limit distribution of the entire dynamics. A precise upper bound of this approximation is given. The states in the support of this approximation are the approximate stochastically stable states. The approach is applied to a model of conjectural variation and imitation in Cournot oligopoly. If behavioural change takes place infrequently, the Walrasian conjecture and quantity is the unique approximate stochastically stable state.
Service quality determinants of the container haulage industry: an empirical study in Malaysia

The international shipping trade has emerged to be a growth enabler of globalisation, playing a crucial role in the economy and development of many countries, such as Malaysia. To support the industry, the Malaysian Government liberalised policies to develop the container haulage industry, but some issues still exist. The present study focuses on retention behaviour of consignees who use container haulage services in major Malaysian ports. The findings reveal that customers retain the same container haulage company provided overall service quality is maintained at an acceptable standard. The safety and security of goods transported by haulage companies are the highest priorities of customers. However, customers also reported that haulage service providers need to show professionalism in human resources competency, employee-customer relations, appropriate pricing for expected service delivery, and information databases.
Genesis and fate of the perireticular thalamic nucleus during early development

A striking feature of the internal capsule during early development is that it is full of small neurones. Later, this group of neurones, called the perireticular thalamic nucleus, appears to have reduced in size, and only a few scattered cells are seen. In an effort to understand better the developmental history of the perireticular nucleus this study examines: i) the period of cell generation in the nucleus, ii) the magnitude of cell loss in the nucleus, and iii) the subsequent fate of cells in the nucleus during development.
Nanomaterials for Engineering Stem Cell Responses

Recent progress in nanotechnology has stimulated the development of multifunctional biomaterials for tissue engineering applications. Synergistic interactions between nanomaterials and stem cell engineering offer numerous possibilities to address some of the daunting challenges in regenerative medicine, such as controlling trigger differentiation, immune reactions, limited supply of stem cells, and engineering complex tissue structures. Specifically, the interactions between stem cells and their microenvironment play key roles in controlling stem cell fate, which underlines therapeutic success. However, the interactions between nanomaterials and stem cells are not well understood, and the effects of the nanomaterials shape, surface morphology, and chemical functionality on cellular processes need critical evaluation. In this Review, focus is put on recent development in nanomaterial–stem cell interactions, with specific emphasis on their application in regenerative medicine. Further, the emerging technologies based on nanomaterials developed over the past decade for stem cell engineering are reviewed, as well as the potential applications of these nanomaterials in tissue regeneration, stem cell isolation, and drug/gene delivery. It is anticipated that the enhanced understanding of nanomaterial–stem cell interactions will facilitate improved biomaterial design for a range of biomedical and biotechnological applications.
Modeling and simulation of chemomechanics at the cell-matrix interface

Chemomechanical characteristics of the extracellular materials with which cells interact can have a profound impact on cell adhesion and migration. To understand and modulate such complex multiscale processes, a detailed understanding of the feedback between a cell and the adjacent microenvironment is crucial. Here, we use computational modeling and simulation to examine the cell-matrix interaction at both the molecular and continuum lengthscales. Using steered molecular dynamics, we consider how extracellular matrix (ECM) stiffness and extracellular pH influence the interaction between cell surface adhesion receptors and extracellular matrix ligands, and we predict potential consequences for focal adhesion formation and dissolution. Using continuum-level finite element simulations and analytical methods to model cell-induced ECM deformation as a function of ECM stiffness and thickness, we consider the implications toward design of synthetic substrata for cell biology experiments that intend to decouple chemical and mechanical cues.
Image Characterization by Morphological Hierarchical Representations

Cette these porte sur l'extraction de descripteurs hierarchiques et multi-echelles d'images, en vue de leur interpretation, caracterisation et segmentation. Elle se decompose en deux parties.La premiere partie expose des elements theoriques et methodologiques sur l'obtention de classifications hierarchiques des nœuds d'un graphe value aux aretes. Ces methodes sont ensuite appliquees a des graphes representant des images pour obtenir differentes methodes de segmentation hierarchique d'images. De plus, nous introduisons differentes facons de combiner des segmentations hierarchiques. Nous proposons enfin une methodologie pour structurer et etudier l'espace des hierarchies que nous avons construites en utilisant la distance de Gromov-Hausdorff entre elles.La seconde partie explore plusieurs applications de ces descriptions hierarchiques d'images. Nous exposons une methode pour apprendre a extraire de ces hierarchies une bonne segmentation de facon automatique, etant donnes un type d'images et un score de bonne segmentation. Nous proposons egalement des descripteurs d'images obtenus par mesure des distances inter-hierarchies, et exposons leur efficacite sur des donnees reelles et simulees. Enfin, nous etendons les potentielles applications de ces hierarchies en introduisant une technique permettant de prendre en compte toute information spatiale a priori durant leur construction.
Bidirectional data transfer based asynchronous VLSI system using multiple-valued current mode logic

A new asynchronous data transfer scheme using multiple-valued 2-color 1-phase coding, called a bidirectional data transfer scheme, is proposed for a high-performance and low-power VLSI system. Valid data signals of "0" or "1" are represented by binary dual-rail complementary codes, (0,1) and (1,0), and "ODD" and "EVEN" colors are represented by binary dual-rail codes, (0,0) and (1,1), respectively. Control signals from both a transmitter and a receiver are represented by dual-rail multiple-valued coding with superposition of data and color signals. The use of dual-rail coding makes it easy to detect EVEN and ODD information by calculating the sum of dual-rail codes, even when data and color information are mixed on the same wires in asynchronous data transfer Since a linear-summation can be implemented by wiring without active devices in multiple-valued bidirectional current-mode circuitry, the proposed circuit for asynchronous control becomes simple. It is evaluated in a 0.18 /spl mu/m CMOS technology that the switching speed of the proposed asynchronous data transfer scheme is about 1.6-times faster than that of the corresponding binary CMOS implementation under the normalized power dissipation.
Tough Teammates: Training Grit and Optimism Together Improves Performance in Professional Footballers

Many psychological constructs under the heading of Positive Psychology are important to the careers of athletes and other high level performers. Grit and optimism have both been linked to performance outcomes in multiple disciplines, and interventions have been trialed to develop these factors in individuals and groups, with varying levels of success. Using an adapted version of the Penn Resiliency Program (PRP) and Master Resilience Training (MRT) programs used to train resilience in both education and military settings, we implemented a mental toughness training intervention with a group of professional football players (n = 22) and also followed a control group (n = 13) in the same team. Results show the training was effective at increasing optimism but not grit, and had a positive impact on performance over the following season that was moderated by previous performance levels. Correlations and regression models also showed that optimism and grit together were subsequently predictive of consistency and performance. We discuss the moderating effects of the player’s pre-training level of ability as well as potential leadership effects, and offer recommendations for future research into the links between optimism, grit and performance.
(In)securitization and illiberal practices on the fringe of the EU

ABSTRACT Illiberal practices of liberal regimes have been extensively studied by critical security studies. The literature on risk emphasises the idea of imminent dangers and the logic of worst-case scenarios, which eventually unsettle the balance between security and liberty by always favouring the former in its most coercive and exceptional forms. This paper, by drawing on (in)securitization theory, attempts to explain how particular illiberal practices with respect to the control and management of immigration on the fringe of the EU become normalised. It argues that (in)securitization of immigration and illiberal practices are effects of the very functioning of a transnational field of (in)security professionals that are produced through the structural competition between different actors of this field over the definition of security and the appropriate control and management of immigration. In this respect, it uses Greece as a case study and draws on material gathered through interviews with Greek security professionals in Athens, Lesvos, Orestiada, and Alexandroupoli, and analysis of their discourse in dissertations they prepared during their study in police academies.
An Investigation of Gen-Y's Online Hotel Information Search: The Case of Hong Kong

The Internet has made searching for hotel room information and making online reservations common practices among hotel guests. Despite constantly changing consumer behavior and widespread application of online hotel information sources, limited studies have been conducted to examine the online sources used frequently by customers and the related attributes of such sources. As such, drawing from an online questionnaire survey with 205 respondents, findings in this study indicate that there are no socio-demographic effects on future purchase intention of Generation (Gen) Y travelers. Moreover, websites of suppliers (e.g. official websites of hotels), travel intermediaries (e.g. Hotels.com), and social media (e.g. TripAdvisor) are the three major types of websites used by Gen Y hotel guests. Travel intermediary websites are often used to search for hotel information, whereas social media websites are used to make reservations. Based on these findings, implications for hotel managers are discussed.