Miracle-dz/UniFAR-FTUs huggingface dataset:
Antiproliferative Effects of Continued Mitogen-Activated Protein Kinase Pathway Inhibition following Acquired Resistance to BRAF and/or MEK Inhibition in Melanoma

Inhibitors of the mitogen-activated protein kinases (MAPK), BRAF, and MAP–ERK kinase (MEK) induce tumor regression in the majority of patients with BRAF-mutant metastatic melanoma. The clinical benefit of MAPK inhibitors is restricted by the development of acquired resistance with half of those who benefit having progressed by 6 to 7 months and long-term responders uncommon. There remains no agreed treatment strategy on disease progression in these patients. Without published evidence, fears of accelerated disease progression on inhibitor withdrawal have led to the continuation of drugs beyond formal disease progression. We now show that treatment with MAPK inhibitors beyond disease progression can provide significant clinical benefit, and the withdrawal of these inhibitors led to a marked increase in the rate of disease progression in two patients. We also show that MAPK inhibitors retain partial activity in acquired resistant melanoma by examining drug-resistant clones generated to dabrafenib, trametinib, or the combination of these drugs. All resistant sublines displayed a markedly slower rate of proliferation when exposed to MAPK inhibitors, and this coincided with a reduction in MAPK signaling, decrease in bromodeoxyuridine incorporation, and S-phase inhibition. This cytostatic effect was also associated with diminished levels of cyclin D1 and p-pRb. Two short-term melanoma cultures generated from resistant tumor biopsies also responded to MAPK inhibition, with comparable inhibitory changes in proliferation and MAPK signaling. These data provide a rationale for the continuation of BRAF and MEK inhibitors after disease progression and support the development of clinical trials to examine this strategy. Mol Cancer Ther; 12(7); 1332–42. ©2013 AACR.
. Two roles for attention in

This paper presents MetriCat , a structural description model of the human capacity to recognize objects both as members of a general class (e.g., "chair") and as specific instances ("my office chair"). MetriCat codes the attributes of an object's parts and their relations in a nonlinear fashion that captures the desirable properties of both categorical and metric representations of shape, and provides a natural basis for recognition at both the class and instance levels. Like previous structural description models (e.g., Hummel & Biederman, 1992), MetriCat represents part attributes and relations independently, dynamically binding them into structural descriptions. The resulting representation suggests two roles for visual attention in shape recognition: attention for binding and attention for signal-to-noise control. MetriCat implements both functions as special cases of a single mechanism for controlling the synchrony relations among units representing separate object parts. The model accounts for the time course of class-and instance-level classification, and makes several predictions about the relationships between attention, time, and levels of classification.
Errors in Variables and Panel Data: The Labour Demand Response to Permanent Changes in Output

This paper examines panel data modelling with latent variables in analyzing log-linear relations between inputs and output of firms. Our particular focus is on (i) the "increasing returns to scale puzzle" for labour input and (ii) the GMM estimation in the context of errors-in-variables and panel data. The IV's used for the observed log-differenced output are log output (in level form) for other years than those to which the difference(s) refer. Flexible assumptions are made about the second order moments of the errors, the random coefficients, and other latent variables, allowing, inter alia, for arbitrary heteroskedasticity and autocorrelation up to the first order of the errors-in-variables. We compare OLS, 2SLS, and GMM estimates of the average input response elasticity (which in some cases can be interpreted as an average inverse scale elasticity), and investigate whether year specific estimates differ substantially from those obtained when data for all years are combined. The results confirm the "increasing returns to scale puzzle" for labour input (measured in three different ways), but indicate approximately constant returns to scale when we consider the material input response. This indicates non-homotheticity of the production technology.
Risk Factors for Recurrence of Symptomatic Common Bile Duct Stones after Cholecystectomy

Purpose. The recurrence of CBD stone is still observed in a considerable number of patients. The study was to evaluate the risk factors for recurrence of symptomatic CBD stone in patients who underwent cholecystectomy after the removal of CBD stone. Methods. The medical records of patients who underwent removal of CBD stone with subsequent cholecystectomy were reviewed. The risk factors for the recurrence of symptomatic CBD stone were compared between the recurrence and the nonrecurrence group. Results. The mean follow-up period was 40.6 months. The recurrence of symptomatic CBD stones was defined as the detection of bile duct stones no sooner than 6 months after complete clearance of CBD stones, based on symptoms or signs of biliary complication. 144 patients (68 males, 47.2%) were finally enrolled and their mean age was 59.8 (range: 26~86) years. The recurrence of CBD stone occurred in 15 patients (10.4%). The mean period until first recurrence was 25.9 months. The presence of type 1 or 2 periampullary diverticulum and multiple CBD stones were the independent risk factors. Conclusion. For the patients with type 1 or 2 periampullary diverticulum or multiple CBD stones, careful followup is needed for the risk in recurrence of symptomatic CBD stone.
Methylation-Associated Gene Silencing of RARB in Areca Carcinogens Induced Mouse Oral Squamous Cell Carcinoma

Regarding oral squamous cell carcinoma (OSCC) development, chewing areca is known to be a strong risk factor in many Asian cultures. Therefore, we established an OSCC induced mouse model by 4-nitroquinoline-1-oxide (4-NQO), or arecoline, or both treatments, respectively. These are the main two components of the areca nut that could increase the occurrence of OSCC. We examined the effects with the noncommercial MCGI (mouse CpG islands) microarray for genome-wide screening the DNA methylation aberrant in induced OSCC mice. The microarray results showed 34 hypermethylated genes in 4-NQO plus arecoline induced OSCC mice tongue tissues. The examinations also used methylation-specific polymerase chain reaction (MS-PCR) and bisulfite sequencing to realize the methylation pattern in collected mouse tongue tissues and human OSCC cell lines of different grades, respectively. These results showed that retinoic acid receptor β (RARB) was indicated in hypermethylation at the promoter region and the loss of expression during cancer development. According to the results of real-time PCR, it was shown that de novo DNA methyltransferases were involved in gene epigenetic alternations of OSCC. Collectively, our results showed that RARB hypermethylation was involved in the areca-associated oral carcinogenesis.
Selecting Superior De Novo Transcriptome Assemblies: Lessons Learned by Leveraging the Best Plant Genome

Whereas de novo assemblies of RNA-Seq data are being published for a growing number of species across the tree of life, there are currently no broadly accepted methods for evaluating such assemblies. Here we present a detailed comparison of 99 transcriptome assemblies, generated with 6 de novo assemblers including CLC, Trinity, SOAP, Oases, ABySS and NextGENe. Controlled analyses of de novo assemblies for Arabidopsis thaliana and Oryza sativa transcriptomes provide new insights into the strengths and limitations of transcriptome assembly strategies. We find that the leading assemblers generate reassuringly accurate assemblies for the majority of transcripts. At the same time, we find a propensity for assemblers to fail to fully assemble highly expressed genes. Surprisingly, the instance of true chimeric assemblies is very low for all assemblers. Normalized libraries are reduced in highly abundant transcripts, but they also lack 1000s of low abundance transcripts. We conclude that the quality of de novo transcriptome assemblies is best assessed through consideration of a combination of metrics: 1) proportion of reads mapping to an assembly 2) recovery of conserved, widely expressed genes, 3) N50 length statistics, and 4) the total number of unigenes. We provide benchmark Illumina transcriptome data and introduce SCERNA, a broadly applicable modular protocol for de novo assembly improvement. Finally, our de novo assembly of the Arabidopsis leaf transcriptome revealed ~20 putative Arabidopsis genes lacking in the current annotation.
Making the News

Increasingly, scholars have come to see the news media as playing a pivotal role in shaping whether social movements are able to bring about broader social change. By drawing attention to movements’ issues, claims, and supporters, the news media can shape the public agenda by influencing public opinion, authorities, and elites. Why are some social movement organizations more successful than others at gaining media coverage? Specifically, what organizational, tactical, and issue characteristics enhance media attention? We combine detailed organizational survey data from a representative sample of 187 local environmental organizations in North Carolina with complete news coverage of those organizations in 11 major daily newspapers in the two years following the survey (2,095 articles). Our analyses reveal that local news media favor professional and formalized groups that employ routine advocacy tactics, mobilize large numbers of people, and work on issues that overlap with newspapers’ focus on local economic growth and well-being. Groups that are confrontational, volunteer-led, or advocate on behalf of novel issues do not garner as much attention in local media outlets. These findings have important implications and challenge widely held claims about the pathways by which movement actors shape the public agenda through the news media.
The Econometrics of the Hodrick-Prescott Filter

Abstract The Hodrick-Prescott (HP) filter is a commonly used tool in macroeconomics used to extract a trend component from a time series. In this paper, we derive a new representation of the transformation of the data that is implied by the HP filter. This representation highlights that the HP filter is a symmetric weighted average plus a number of adjustments that are important near the beginning and end of the sample. The representation allows us to carry out a rigorous analysis of properties of the HP filter without using the ARMA-based approximation that has been used previously in the literature. Using this new representation, we characterize the large T behavior of the HP filter and find conditions under which it is asymptotically equivalent to a symmetric weighted average with weights independent of sample size. We also find that the cyclical component of the HP filter possesses weak dependence properties when the HP filter is applied to a stationary mixing process, a linear deterministic trend process, or a process with a unit root. This provides the first formal justification of the use of the HP filter as a tool to achieve weak dependence in a time series. In addition, a large smoothing parameter approximation to the HP filter is derived, and using this approximation, we find an alternative justification for the procedure given in Ravn and Uhlig (2002) for adjusting the smoothing parameter for the data frequency.
Reduced transduction efficiency of adenoviral vectors expressing human p53 gene by repeated transduction into glioma cells in vitro.

PURPOSE Recombinant adenoviral vectors are widely used in clinical and experimental studies to treat malignant tumors. Recently, host immune responses have been proposed as a major limitation in using adenoviral vectors for repeated gene delivery. We demonstrate another limitation unrelated to host immunity. EXPERIMENTAL DESIGN We repeatedly transduced an adenoviral vector expressing the human p53 gene (AxCIhp53) into U373MG, a p53-susceptible cell line, and established the AxCIhp53-resistant cell line U373R. Most U373R cells survived even after AxCIhp53 treatment due to reduced transduction efficiency. Expression levels of adenovirus receptors were estimated to investigate the cause of reduced transduction efficiency. The mutant vector was used to overcome the resistance. RESULTS The transduction efficiency of an adenoviral vector possessing the reporter LacZ gene (AxCAZ2-F/wt) for U373R cells was 25.4-fold less than that for parent cells. The expression levels of integrins alpha(v)beta(3) and alpha(v)beta(5) were found to be decreased in U373R cells without affecting the expression levels of Coxsackievirus and adenovirus receptor. The mutant vector AxCAZ2-F/K20, with a linker and a stretch of 20 lysine residues at the COOH-terminal of the fiber protein, improved the transduction efficiency of U373R cells to 12.6-fold of that of AxCAZ2-F/wt. A mutant vector carrying the p53 gene, AxCAhp53-F/K20, dramatically induced apoptosis in U373R cells. CONCLUSIONS Glioma cells expressing low levels of adenovirus receptors might survive and proliferate to recur after repeated adenoviral transduction, even if the adenoviral transduction is effective at first. Changing the tropism of vectors is a potent method to overcome resistance.
The price of flexibility

Flexibility and customizability are central to the perceived advantages of the growth in technological powers. But this and other vectors of t ethnological change, when used clumsily, create new burdens and complexities for beleaguered human practitioners responsible for achieving goals within some field of activity. “Intelligent interfaces” are sometimes seen as a solution to the growing demands of highly technological and highly automat ed fields of activity. However, data from a variety of sources indicates that a technology driven approach to the development of intelligent interfaces is likely to provide the illusion of assistance while creating a new layer of burdens and complexities. What distinguishes technological flexibilities that are used to increase the range of practitioner adaptive response to the variability y resident in the field of activity from technological flexibilities that simply create new burdens on the practitioner especially at high tempo, high criticality y periods?
Structural Brain Changes Following Left Temporal Low-Frequency rTMS in Patients with Subjective Tinnitus

Repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has been used to treat patients with subjective tinnitus. While rTMS is known to induce morphological changes in healthy subjects, no study has investigated yet whether rTMS treatment induces grey matter (GM) changes in tinnitus patients as well, whether these changes are correlated with treatment success, and whether GM at baseline is a useful predictor for treatment outcome. Therefore, we examined magnetic resonance images of 77 tinnitus patients who were treated with rTMS of the left temporal cortex (10 days, 2000 stimuli/day, 1 Hz). At baseline and after the last treatment session high-resolution structural images of the brain were acquired and tinnitus severity was assessed. For a subgroup of 41 patients, additional brain scans were done after a follow-up period of 90 days. GM changes were analysed by means of voxel based morphometry. Transient GM decreases were detectable in several brain regions, especially in the insula and the inferior frontal cortex. These changes were not related to treatment outcome though. Baseline images correlated with change in tinnitus severity in the frontal cortex and the lingual gyrus, suggesting that GM at baseline might hold potential as a possible predictor for treatment outcome.
The effect of affective response to corporate social irresponsibility on consumer resistance behaviour: validation of a dual-channel model

ABSTRACT This paper delineates a dual-channel model of consumer resistance towards corporate social irresponsibility. The model assumes a conditional mediational relationship among affective response to corporate social irresponsibility and ethical judgement as drivers of consumers’ inclination towards boycotting, protesting and negative word-of-mouth. Mediation-analysis results are largely in line with the model hypotheses: Affective response to corporate social irresponsibility solely has a significant direct effect on resistance inclination of consumers with a low preference for ethical products. Moreover, contractualistic and moral equity (utilitarian) judgement mediate(s) the effect of affective response on resistance intention for consumers with high (low) ethical product preferences. Based on the empirical findings, the paper presents practical implications and avenues for future research.
GIS and Students as Scientists Constructivist Approaches to Science Curriculum Restructuring

Introduction This paper considers student use of geographical information system software as a tool for teachers to restructure components of their middle school science curriculum from constructivist perspectives. The paper begins with a rational for adopting such teaching and learning approaches which is followed by a description of a current curriculum case in a Texas middle school. Following this is an outline of an approach to restructuring science teaching in this case, supplemented by a separate document utilizing these approaches and theory in the form of activities for a middle school science teacher. This independent document, entitled GIS and Students as Scientists: Constructivist Approaches to Science Curriculum Restructuring-Inservice Supplement, is a stand alone inservice activity workbook. Finally, a description of barriers to consider in utilizing such an approach to curriculum restructuring is presented. Pedagogy in the United States has been dominated by the behavioristic model, according to many cognitive psychologists (Yager, 1995), despite Piaget's research on cognitive operations (Duit & Treagust, 1998). Behavioristic approaches to teaching and learning follow a theory that focuses primarily on objectively observable behaviors and leaves little room for cognitive activity and understanding. Learning, in the behavioristic paradigm, is simply the acquisition of new behavior based on stimuli and reinforcements provided by the teacher (Yager, 1995; On Purpose, 1998). Behaviorism uses conditioning to develop responses. The most common examples of conditioning include classic conditioning as seen in 'Pavlov's dogs' and operant conditioning, as seen in B. F. Skinner's demonstrations of teaching pigeons to dance (On Purpose, 1998). However, if "understanding, interpretation, synthesis, and the ability to use information in new situations is our goal in education, a behaviorist approach is not successful" (Yager, 1995, p. 39). Yager stated, "there is little evidence that meaning can be transferred directly to learners unless learners engage themselves in a thought process—often initiated by a problem or discrepant event" (1995, p. 37). Learning is less dependent upon teacher presentations, than it is upon how a student processes information s/he encounters and assimilates that information based on preconceived notions and personal mental models of science concepts each having a different perception of the world, mental models that vary, and different social conditions, need a variety of opportunities to "achieve a more 'scientific' understanding of a new concept" (Ward, 1995, p. 9). It is through a student's "dynamic process of building, organizing, and elaborating" (Glynn & Duit, 1995, p. 3) upon their …
A Fast Algorithm for Sparse Reconstruction Based on Shrinkage, Subspace Optimization, and Continuation

We propose a fast algorithm for solving the $\ell_1$-regularized minimization problem $\min_{x\in\mathbb{R}^n}\mu\|x\|_1+\|Ax-b\|^2_2$ for recovering sparse solutions to an undetermined system of linear equations $Ax=b$. The algorithm is divided into two stages that are performed repeatedly. In the first stage a first-order iterative “shrinkage” method yields an estimate of the subset of components of $x$ likely to be nonzero in an optimal solution. Restricting the decision variables $x$ to this subset and fixing their signs at their current values reduces the $\ell_1$-norm $\|x\|_1$ to a linear function of $x$. The resulting subspace problem, which involves the minimization of a smaller and smooth quadratic function, is solved in the second phase. Our code FPC_AS embeds this basic two-stage algorithm in a continuation (homotopy) approach by assigning a decreasing sequence of values to $\mu$. This code exhibits state-of-the-art performance in terms of both its speed and its ability to recover sparse signals.
An information literacy teaching model for Vietnam’s schools

Purpose This study aims to identify the ways in which information literacy (IL) in-practice initiatives are framed for Vietnam’s upper secondary students and to suggest an appropriate IL teaching model for schools in the country. Design/methodology/approach The research used a qualitative multiple case study approach, including two phases of data collection. The first phase gathered data from semi-structured student interviews. The second phase included semi-structured professional interviews and an analysis of documents. Findings The research found that time pressure, teaching method, resource issues, students’ awareness of IL and support from family are challenges for the development of IL programmes. These factors impinge upon the development of an IL teaching model for Vietnam’s upper secondary schools. Research limitations/implications The focus of this study was limited to two schools to gain the depth of data needed to provide a holistic picture of the practice of IL teaching in Vietnam’s upper secondary schools. Practical implications This study could provide some guidance to the Ministry of Education and Training in the development of educational policies and initiatives through identifying the possible contributions of IL to Vietnam’s education system. Originality/value The study provides an understanding of the development of IL in the education system in transition, from a didactic to a constructivist approach.
SHIV : Reducing Supervisor Burden using Support Vectors for Efficient Learning from Demonstrations in High Dimensional State Spaces

Online learning from demonstration algorithms, such as DAgger, can learn policies for problems where the system dynamics and the cost function are unknown. However, during learning, they impose a burden on supervisors to respond to queries each time the robot encounters new states while executing its current best policy. Algorithms such as MMD-IL reduce supervisor burden by filtering queries with insufficient discrepancy in distribution and maintaining multiple policies. We introduce the SHIV algorithm (Svm-based reduction in Human InterVention), which converges to a single policy and reduces supervisor burden in non-stationary high dimensional state distributions. To facilitate scaling and outlier rejection, filtering is based on distance to an approximate level set boundary defined by a One Class support vector machine. We report on experiments in three contexts: 1) a driving simulator with a 27,936 dimensional visual feature space, 2) a push-grasping in clutter simulation with a 22 dimensional state space, and 3) physical surgical needle insertion with a 16 dimensional state space. Results suggest that SHIV can efficiently learn policies with equivalent performance requiring up to 70% fewer queries.