Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab.

CONTEXT Patients with metastatic colorectal cancer who have KRAS codon 12- or KRAS codon 13-mutated tumors are presently excluded from treatment with the anti-epidermal growth factor receptor monoclonal antibody cetuximab. OBJECTIVE To test the hypothesis that KRAS codon 13 mutations are associated with a better outcome after treatment with cetuximab than observed with other KRAS mutations. DESIGN, SETTING, AND PATIENTS We studied the association between KRAS mutation status (p.G13D vs other KRAS mutations) and response and survival in a pooled data set of 579 patients with chemotherapy-refractory colorectal cancer treated with cetuximab between 2001 and 2008. Patients were included in the CO.17, BOND, MABEL, EMR202600, EVEREST, BABEL, or SALVAGE clinical trials or received off-study treatment. Univariate and multivariate analyses, adjusting for possible prognostic factors and data set, were performed. The effect of the different mutations was studied in vitro by constructing isogenic cell lines with wild-type KRAS, p.G12V, or p.G13D mutant alleles and treating them with cetuximab. MAIN OUTCOME MEASURES The main efficacy end point was overall survival. Secondary efficacy end points were response rate and progression-free survival. RESULTS In comparison with patients with other KRAS-mutated tumors, patients with p.G13D-mutated tumors (n = 32) treated with cetuximab had longer overall survival (median, 7.6 [95% confidence interval {CI}, 5.7-20.5] months vs 5.7 [95% CI, 4.9-6.8] months; adjusted hazard ratio [HR], 0.50; 95% CI, 0.31-0.81; P = .005) and longer progression-free survival (median, 4.0 [95% CI, 1.9-6.2] months vs 1.9 [95% CI, 1.8-2.8] months; adjusted HR, 0.51; 95% CI, 0.32-0.81; P = .004). There was a significant interaction between KRAS mutation status (p.G13D vs other KRAS mutations) and overall survival benefit with cetuximab treatment (adjusted HR, 0.30; 95% CI, 0.14-0.67; P = .003). In vitro and mouse model analysis showed that although p.G12V-mutated colorectal cells were insensitive to cetuximab, p.G13D-mutated cells were sensitive, as were KRAS wild-type cells. CONCLUSIONS In this analysis, use of cetuximab was associated with longer overall and progression-free survival among patients with chemotherapy-refractory colorectal cancer with p.G13D-mutated tumors than with other KRAS-mutated tumors. Evaluation of cetuximab therapy in these tumors in prospective randomized trials may be warranted.
Design and control of tapping mode atomic force microscope in liquid utilizing optical pickup system

In this work, we propose a fluid tapping mode atomic force microscopy (AFM) implemented by a DVD pickup head. The use of DVD pickup head minimizes the volume of the hardware system, and thus reduces the measurement error caused by heat expansion. In order to realize the system mentioned above, we design a Q-controller to modulate the interaction force between the tip and the sample. Increasing the quality factor will overcome the problem with high damping ratio in the fluid which makes the probe hard to oscillate. Because of the reduction of the tip-sample force, the sample surface will not be hurt by the tip. Therefore, we can use the AFM to scan soft sample, and obtain more realistic topography. Traditionally, people use proportion-integration controller to control the system. Users need to tune this kind of controller manually, and hence the quality of the scan images is highly related to userspsila experiences. To overcome this problem, we design an adaptive sliding-mode controller to improve the scanning capability and robustness. For testing the system capability, we will have a series of numerical simulations.
Do Not Panic! Enhancing Service Recovery of Nursing Services

Service recovery has been an important issue due to broader social and economic context that shows greater demand for health, care and support which can be concluded that it is critical to study the health care services. Predicting that factors such as top management leadership, teamwork, empowerment, training and commitment is critical to be understood because all these factors will affect the motivation and attitude of employees toward service recovery. Furthermore, employee is one of the source of sustainable competitive advantage to organisations. Nursing staffs are the ones who have variety of jobs to perform and need to juggle with many jobs at many places in the medical profession. Hence, there is no doubt that failure in their service might occur and service recovery is very crucial to make sure that nurses will perform better in-service recovery. This study, therefore, aims to determine the factors influencing service recovery among public nurses. Nurses from various public hospitals in Seberang Perai Utara, Pulau Pinang were chosen as respondents for this study. A total number of 400 questionnaires were distributed to respondents using simple random sampling method. Only 368 questionnaires were returned and used for analysis. The results of correlation analysis and regression analysis have shown that three independent variables (empowerment, training and commitment) had a significant relationship and influenced service recovery. In conclusion, the findings in this study revealed that nurse’s commitment is the most critical factors in service recovery.
Randomized Phase II trial of paclitaxel plus valproic acid vs paclitaxel alone as second-line therapy for patients with advanced gastric cancer

The standard regimen of second-line chemotherapy for patients with unresectable gastric cancer has not been established. However, weekly paclitaxel (wPTX) has become the preferable second-line chemotherapy in Japan. Histone deacetylase (HDAC) inhibitors have been shown to have antiproliferative activity through cell-cycle arrest, differentiation, and apoptosis in gastric cancer cells. One HDAC inhibitor, valproic acid (VPA), also inhibits tumor growth by inducing apoptosis, and enhances the efficacy of paclitaxel in a mouse xenograft model of gastric cancer. wPTX plus VPA as a second-line chemotherapy is expected to improve survival in gastric cancer patients. A multicenter randomized Phase II study was conducted to compare the effects of wPTX plus VPA and wPTX alone. A total of 66 patients participated in this study. The primary end point of the study was overall survival, and secondary end points were progression-free survival, response rate, and assessment of peripheral neuropathy.
A Structural Basis for BRD2/4-Mediated Host Chromatin Interaction and Oligomer Assembly of Kaposi Sarcoma-Associated Herpesvirus and Murine Gammaherpesvirus LANA Proteins

Kaposi sarcoma-associated herpesvirus (KSHV) establishes a lifelong latent infection and causes several malignancies in humans. Murine herpesvirus 68 (MHV-68) is a related γ2-herpesvirus frequently used as a model to study the biology of γ-herpesviruses in vivo. The KSHV latency-associated nuclear antigen (kLANA) and the MHV68 mLANA (orf73) protein are required for latent viral replication and persistence. Latent episomal KSHV genomes and kLANA form nuclear microdomains, termed ‘LANA speckles’, which also contain cellular chromatin proteins, including BRD2 and BRD4, members of the BRD/BET family of chromatin modulators. We solved the X-ray crystal structure of the C-terminal DNA binding domains (CTD) of kLANA and MHV-68 mLANA. While these structures share the overall fold with the EBNA1 protein of Epstein-Barr virus, they differ substantially in their surface characteristics. Opposite to the DNA binding site, both kLANA and mLANA CTD contain a characteristic lysine-rich positively charged surface patch, which appears to be a unique feature of γ2-herpesviral LANA proteins. Importantly, kLANA and mLANA CTD dimers undergo higher order oligomerization. Using NMR spectroscopy we identified a specific binding site for the ET domains of BRD2/4 on kLANA. Functional studies employing multiple kLANA mutants indicate that the oligomerization of native kLANA CTD dimers, the characteristic basic patch and the ET binding site on the kLANA surface are required for the formation of kLANA ‘nuclear speckles’ and latent replication. Similarly, the basic patch on mLANA contributes to the establishment of MHV-68 latency in spleen cells in vivo. In summary, our data provide a structural basis for the formation of higher order LANA oligomers, which is required for nuclear speckle formation, latent replication and viral persistence.
Influence of Excess 1/f Noise on Channel Capacity

This paper deals with new analytical and experimental aspects of a channel’s capacity in the presence of excess nonwhite Gaussian noise with long-range dependencies described by the Hurst parameter H . Shannon’s theory of information based on the assumptions given by the Boltzmann | Gibbs extensive thermodynamical basis, does not allow description of many different phenomena directly connected with the ideas of a complex systems approach. This theory is also a basis of many considerations in communication, but a new approach to transmission channels is needed. The transmission channels are no longer simple systems built with only one wire connection, but consist of many different transmission media. For each type of partial connection in such channels there are many various interferences that influence some parts of the channel in different ways. We suggest that in many cases the real capacity of the whole channel can no longer be determined by Shannon’s equation without taking into account the problem of excess 1 ë f noise, which appears as an intrinsic feature of dynamically packet switched networks. The ideas presented in this paper show how the complex system approach can provide a good perspective for analyzing the whole transmission channel.
Scientific Sketching for Collaborative VR Visualization Design

We present four studies investigating tools and methodologies for artist-scientist-technologist collaboration in designing multivariate virtual reality (VR) visualizations. Design study 1 identifies the promise of 3D interfaces for rapid VR design and also establishes limitations of the particular tools tested with respect to precision and support for animation. Design study 2 explores animating artist-created visualization designs with scientific 3D fluid flow data. While results captured an accurate sense of flow that was advantageous as compared to the results of study 1, the potential for visual exploration using the design tools tested was limited. Design study 3 reveals the importance of a new 3D interface that overcomes the precision limitation found in study 1 while remaining accessible to artist collaborators. Drawing upon previous results, design study 4 engages collaborative teams in a design process that begins with traditional paper sketching and moves to animated interactive VR prototypes "sketched" by designers in VR using interactive 3D tools. Conclusions from these four studies identify important characteristics of effective artist-accessible VR visualization design tools and lead to a proposed formalized methodology for successful collaborative design that we expect to be useful in guiding future collaborations. We call this proposed methodology scientific sketching.
Title CHOLESTEROL MODIFIES WATER CONCENTRATION AND DYNAMICS IN PHOSPHOLIPID-BILAYERS-A FLUORESCENCE STUDY USING LAURDAN PROBE Permalink

The effect of cholesterol on the gel, the liquid-crystalline, and mixed phospholipid phases has been studied using the fluorescence properties of 2-dimethylamino-6-lauroyinaphthalene (Laurdan). Laurdan sensitivity to the polarity and to the dynamics of its environment reveals that cholesterol affects phospholipid bilayers in the gel phase by expelling water and by increasing the amount of dipolar relaxation. In the liquid-crystalline phase, the effect of cholesterol is of a reduction of both water concentration and amount of dipolar relaxation. Detailed studies of Laurdan excitation and emission spectral contours as a function of cholesterol concentration show that there are some cholesterol concentrations at which Laurdan spectral properties changes discontinuously. These peculiar cholesterol concentrations are in agreement with recent observations of other workers showing the formation of local order in the liquid-crystalline phase of phospholipids upon addition of phospholipid derivatives of pyrene. A local organization of phospholipids around cholesterol molecule seems to be produced by the presence of peculiar concentrations of cholesterol itself. This local organization is stable enough to be observed during the excited state lifetime of Laurdan of approximately 5-6 ns.
The Impacts of Environmental Regulation on the U.S. Economy

Concern regarding the economic impacts of environmental regulations has been part of the public dialogue since the beginning of the U.S. EPA. Even as large improvements in environmental quality occurred, government and academia began to examine the potential consequences of regulation for economic growth and productivity. In general, early studies found measurable but not severe effects on the overall national economy. While price increases due to regulatory requirements outweighed the stimulative effect of investments in pollution abatement, they nearly offset one another. However, these studies also highlighted potentially substantial effects on local labor markets due to the regional and industry concentration of plant closures. More recently, a substantial body of work examined industry-specific effects of environmental regulation on the productivity of pollution-intensive firms most likely to face pollution control costs, as well as on plant location and employment decisions within firms. Most econometric-based studies found relatively small or no effect on sector-specific productivity and employment, though firms were less likely to open plants in locations subject to more stringent regulation compared to other U.S. locations. In contrast, studies that used economy-wide models to explicitly account for sectoral linkages and intertemporal effects found substantial sector-specific effects due to environmental regulation, including in sectors that were not directly regulated. It is also possible to think about the overall impacts of environmental regulation on the economy through the lens of benefit-cost analysis. While this type of approach does not speak to how the costs of regulation are distributed across sectors, it has the advantage of explicitly weighing the benefits of environmental improvements against their costs. If benefits are greater than costs, then overall social welfare is improved. When conducting such exercises, it is important to anticipate the ways in which improvements in environmental quality may either directly improve the productivity of economic factors – such as through the increased productivity of outdoor workers – or change the composition of the economy as firms and households change their behavior. If individuals are healthier, for example, they may choose to reallocate their time between work and leisure. While introducing a role for pollution in production and household behavior can be challenging, studies that have partially accounted for this interconnection have found substantial impacts of improvements in environmental quality on the overall economy.
Stochastic Complexity of Bayesian Networks

Bayesian networks arc now used in enormous fields, for example. system diagnosis. data mining, clusterings etc. In spite of wide range of their applications, the statistical properties have not yet bcen clarified because the models are nonidentifiable and non-regular. In a Bayesian network. the set of parameters for a smaller model is an analytic set with singularities in the parameter space of a large model. Because of these singularities, the Fisher information matrices are not positive definite. In other words, the mathematical foundation for learning has not been constructed. In recent years, however, we have developed a method to analyze nonregular models by using algebraic geometry. This method revealed the relation between model's singularities and its statistical properties. In this paper, applying this method to Bayesian networks with latent variables, we clarify the orders of the stochastic complexities. Our result shows that their upper bound is smaller than thc dimension of the parameter space. This means that the Bayesian generalization error is also far smaller than that of a regular model, and that Schwarz's model selection criterion BIC needs to be improved for Bayesian networks.
Aalborg Universitet Parking Space Verification Improving Robustness Using A Convolutional Neural Network

With the number of privately owned cars increasing, the issue of locating an available parking space becomes apparant. This paper deals with the verification of vacant parking spaces, by using a vision based system looking over parking areas. In particular the paper proposes a binary classifier system, based on a Convolutional Neural Network, that is capable of determining if a parking space is occupied or not. A benchmark database consisting of images captured from different parking areas, under different weather and illumination conditions, has been used to train and test the system. The system shows promising performance on the database with an accuracy of 99.71 % overall and is robust to the variations in parking areas and weather conditions.
When Hard Times Take a Toll

Using two waves of data from a national survey of working Americans (N = 1,122), we examine the associations among economic hardship, negative life events, and psychological distress in the context of the family-work interface. Our findings demonstrate that family-to-work conflict mediates the effects of economic hardship and negative events to significant others on distress (net of baseline distress and hardship). Moreover, economic hardship and negative events to significant others moderate the association between family-to-work conflict and distress. While negative events to others exacerbate the positive effect of family-to-work conflict on distress, we find the opposite for economic hardship: The positive association between hardship and distress is weaker at higher levels of family-to-work conflict. These patterns hold across an array of family, work, and sociodemographic conditions. We discuss how these findings refine and extend ideas of the stress process model, including complex predictions related to processes of stress-buffering, resource substitution, and role multiplication.
J ul 2 00 1 Optimal immunisation of complex networks

Complex networks such as the sexual partnership web or the Internet often show a high degree of redundancy and heterogeneity in their connectivity properties. This peculiar connectivity, however, provides an ideal environment for the spreading of biological or digital infective agents. Here we show that the random uniform immu-nisation of individuals does not lead to the eradication of infections in all complex networks. Namely, networks with scale-free properties do not acquire global immunity from major epidemic outbreaks even in the presence of unrealistically high densities of randomly immunised individuals. The absence of any critical immunisation threshold is due to the unbounded connectivity fluctuations of scale-free networks. Successful immunisation strategies can be developed only by taking into account the inhomogeneous connectivity properties of scale-free networks. In particular, targeted immunisation programmes, based on the nodes' connectivity hierarchy, sharply lower the network's vulnerability to epidemic attacks.
CÉLULAS DE OSTEOSSARCOMA HUMANO CYTOTOXIC EFFECT OF SULFORAPHANE IN HUMAN OSTEOSARCOMA CELLS

Osteosarcoma is the most common type of malignant bone tumor. This disease shows high incidence in children and adolescents. Additionally, metastases occurring mainly at the lungs affect a considerable percentage of osteosarcoma patients. Current treatments include surgical resection, chemotherapy, and radiotherapy, but osteosarcoma patients show poor responsiveness to these treatment options. Thus, it is urgent to develop novel treatment approaches. Sulforaphane is a phytochemical that displays chemopreventive and chemotherapeutic activity. Many studies have been shown that sulforaphane modulates many cancer-related events, as susceptibility to carcinogenic agents, cell cycle, apoptosis, angiogenesis, and metastasis. Although well characterized in several tumors, the effects of sulforaphane are still poorly understood in osteosarcoma, as well as the underlying mechanism of action. The aim of this dissertation was to evaluate the potential cytostatic and apoptotic effects of sulforaphane and to unveil the mechanism of action behind these effects. In order to do that, the human osteosarcoma cell line MG-63 was exposed to sulforaphane (in the 0 to 20 μM range) for 24 and 48 h. Parameters as confluence, cell morphology, cell viability, cell cycle, clastogenicity, apoptosis, caspase specific activity, and expression of cell cycle-related genes were analyzed after sulforaphane treatment. Cultures exposed to sulforaphane showed a decrease in confluence, accompanied by alterations in cell morphology. Sulforaphane also induced a doseand time-dependent impairment of cell viability, which can be explained by an increase of apoptotic cells and cytostaticity with G2/M phase arrest. This cell cycle blockage was mediated by Chk2 and CDC25C downregulation, and probably CCNB1 as well as CDK2 downregulation. A clastogenic effect was also detected after 48 h of sulforaphane treatment. These data suggest that sulforaphane should be considered as a chemotherapeutic agent candidate in osteosarcoma treatment, although more studies are needed to shed insight on signaling pathways modulated by sulforaphane, as well as the possible cytotoxicity of this phytochemical on normal osteoblasts. Part of the work described within this dissertation has been submitted for publication in Toxicology and Applied Pharmacology as part of the manuscript Remédios, C. , Costa, M. , Pinto, P., Pinho, F. , Pedrosa, T. , Pinho, S. , Rosár io, F. , Ferreira de Oliveira, J.M. P., Oliveira, H. and Santos, C. (2012) Sulforaphane-ind uced DNA Damage in Osteosarcoma Cells: A Correlation with Oxidative Stress, Cell Cy cle Arrest and Apoptosis.
Runtime detection of activated polychronous neuronal group towards its spatiotemporal analysis

Due to the precise spike timing in neural coding, spiking neural network (SNN) possesses richer spatiotemporal dynamics compared to neural networks with firing rate coding. One of the distinct features of SNN, polychronous neuronal group (PNG), receives much attention from both computational neuroscience and machine learning communities. However, all existing algorithms detect PNGs from the spike recording collected after simulation in an offline manner. There is currently no algorithm that detects PNGs actually being activated in runtime (online manner), which could be potentially used as inputs to higher level neural processing. We propose a runtime detection algorithm particularly for activated PNGs, using PNG readout neurons, to fill this gap. The proposed algorithm can reveal the spatiotemporal PNG patterns embedded in spike trains, which is higher level neuronal dynamics. We demonstrate through an example that for composed input patterns, new PNGs except the constituent PNGs can be easily found using the proposed algorithm. As an important interpretation, we give further insights on how to use PNG readout neurons to construct layered network structure.