Miracle-dz/UniFAR-FTUs huggingface dataset:
Protein Kinase D as a Potential Chemotherapeutic Target for Colorectal Cancer

Protein kinase D (PKD) signaling plays a critical role in the regulation of DNA synthesis, proliferation, cell survival, adhesion, invasion/migration, motility, and angiogenesis. To date, relatively little is known about the potential role of PKD in the development and/or progression of human colorectal cancer. We evaluated the expression of different PKD isoforms in colorectal cancer and investigated the antitumor activity of PKD inhibitors against human colorectal cancer. PKD2 was the dominant isoform expressed in human colon cancer cells. PKD3 expression was also observed but PKD1 expression, at both the RNA and protein levels, was not detected. Suppression of PKD using the small molecule inhibitors CRT0066101 and kb-NB142-70 resulted in low micromolar in vitro antiproliferative activity against multiple human colorectal cancer cell lines. Drug treatment was associated with dose-dependent suppression of PKD2 activation. Incubation with CRT0066101 resulted in G2–M phase arrest and induction of apoptosis in human colorectal cancer cells. Further studies showed that CRT0066101 treatment gave rise to a dose-dependent increase in expression of cleaved PARP and activated caspase-3, in addition to inhibition of AKT and ERK signaling, and suppression of NF-κB activity. Transfection of PKD2-targeted siRNAs resulted in similar effects on downstream pathways as observed with small molecule inhibitors. Daily administration of CRT0066101 resulted in significant inhibition of tumor growth in HCT116 xenograft nude mice. Taken together, our studies show that PKD plays a significant role in mediating growth signaling in colorectal cancer and may represent a novel chemotherapeutic target for the treatment of colorectal cancer. Mol Cancer Ther; 13(5); 1130–41. ©2014 AACR.
Recursive neural network based word topology model for hierarchical phrase-based speech translation

Recursive word topology structure is commonly found in natural language sentences, and discovering this structure can help us to not only identify the units that a sentence contains but also how they interact to form a whole. In this paper, we explore a novel recursive neural network (RNN) based word topology model (WordTM) for hierarchical phrase-based (HPB) speech translation, which captures the topological structure of the words on the source side in a syntactically and semantically meaningful order. Experiments show that our WordTM significantly outperforms the state-of-the-art soft syntactic constraints.
The practical side of working with parent–child interaction therapy with preschool children with language impairments

A common early intervention approach for preschool children with language problems is parent–child interaction therapy (PCIT). PCIT has positive effects for children with expressive language problems. It appears that speech and language therapists (SLTs) conduct this therapy in many different ways. This might be because of the variety of approaches available, the diverse set of families SLTs work with or the different organizational structures. Understanding the critical components of PCIT would enable SLTs to map the variations that are implemented and researchers to evaluate the effects of such variation. This study aimed to identify the potentially critical components of PCIT based on the practical experience of SLTs and to identify SLTs’ rationales for the way they structure PCIT. Both parameters are important for the long term goal, that is, to develop a framework that can be used to support practice. Semi-structured interviews were conducted with 10 SLTs who had at least one year experience in delivering PCIT with preschool children with language impairment. The interviews were transcribed and analysed, using thematic analysis. Analysis of the SLT interview data identified four potentially critical components that underpin the teaching of strategies to parents: parents’ engagement, parents’ understanding, parents’ reflection and therapists’ skills. SLTs suggested that all four components are needed for the successful delivery of PCIT. The reasons that SLTs give for the way in which they structure PCIT are mainly based on organizational constraints, family needs and practicalities. SLTs consider PCIT to be valuable but challenging to implement. A framework that makes explicit these components may be beneficial to support practice.
Alternative energy resource from electric transportation

Electric vehicles, whether powered by batteries, fuel cells, or petrol hybrids, have within them the energy source and power electronics capable of producing the AC electricity that powers our homes and offices. When bidirectional connections are added to allow this electricity to flow from cars to power lines and vice versa, this is referred to as "vehicle-to-grid" power, or V2G . The electric vehicles can then become mobile distributed generation resources, which can be valuable, particularly during peak hour. The Electric Power Research Institute predicts that power from electric-drive vehicles could reduce the global requirement for central station generation capacity by up to 20 percent by the year 2050. The paper describes a power electronics system that can be used to provide the bidirectional power transfer capability of the charger. The proposed bidirectional power converter can also provide reactive power and voltage support which theoretically does not make use of the energy of the energy storage in the EV.
Multi-Agent Planning with Baseline Regret Minimization

We propose a novel baseline regret minimization algorithm for multi-agent planning problems modeled as finite-horizon decentralized POMDPs. It guarantees to produce a policy that is provably at least as good as a given baseline policy. We also propose an iterative belief generation algorithm to efficiently minimize the baseline regret, which only requires necessary iterations so as to converge to the policy with minimum baseline regret. Experimental results on common benchmark problems confirm the benefits of the algorithm compared with the state-of-the-art approaches.
1 Rectal Cancer Epidemiology

Colorectal cancer is the fourth most common cancer in men and the third most common one in women worldwide (Parkin, 2004; Parkin et al., 2005), accounting for approximately 436,000 incident cases and 212,000 deaths in 2008 (Quirke et al., 2011). This cancer has an important economic impact, estimating that in the initial, continuing and last year of life phases of care a total of more than $7 billion were spent (Yabroff et al., 2008). Randomized trials have shown that systematic screening of a target population of suitable age can reduce colorectal cancer by detecting asymptomatic lesions (Center et al., 2009). Although there are differences in the etiologies and epidemiology of colon and rectal cancer (Giovannucci & Wu, 2006), the majority of the studies chose to examine colon and rectum cancers combined. However, a better understanding of these diseases nowadays, shows that these differences have an important impact in their approaches. First of all, the location of the tumours may determines different locations of metastisation. Unlike colon cancers, distal rectal tumours may first metastasize to the lungs because the inferior rectal veins drain into the inferior vena cava rather than into the portal venous system. The histological type can also vary. The vast majority of colorectal tumours are adenocarcinomas but 11-17% are mucinous carcinomas. This type, which has a penchant for the rectum and sigmoid colon, tends to be present at a more advanced stage (Consorti et al., 2000). The carcinoid tumours have a different clinical presentation too, depending on whether they appear in the rectum or in the colon (Marshall & Badnarchuk 1993; Spread et al., 1994). The rectum carcinoids develop at a young age, most of which are less than 2 cm and tend to be indolent. In contrast, colonic carcinoid tumours can be clinically aggressive and often metastise. With a more accurate review, we can see that many habits could influence the development of rectal cancers and not colon cancers. Some studies support the view that family history, as well as the level of physical activity, is a stronger contributor to colon cancer relative to rectal cancer (Wei et al., 2004). The Women’s Health Initiative (a large cohort study) (Paskett et al., 2007) also found a significant link between active cigarette smoking (not passive exposure to cigarette smoke) and rectal but not colon cancer. These differences are important in terms of monitoring and have implications in treatment options, as well. Compared to colon cancers, the sensitivity of CT scan for detection of
Regularized Multivariate Analysis Framework for Interpretable High-Dimensional Variable Selection

Multivariate Analysis (MVA) comprises a collection of tools that play a fundamental role in statistical data analysis. These techniques have become increasingly popular since the proposal of Principal Component Analysis (PCA) in 1901 [1]. PCA was proposed as a simple and efficient way to reduce data dimension by projecting the data over the largest variance directions. As illustrated in Fig. 1, PCA learns from a given dataset a set of projection vectors, so that data can be represented in a low-dimensional space that preserves the directions of the input space where the data shows the largest variance. A typical example to illustrate PCA is face recognition, where the projection vectors are known as eigenfaces [2]. Nevertheless, PCA has been used in many other applications, and can indeed be considered as one of the most widely-used tools for feature extraction.
The Role of mGlu Receptors in Hippocampal Plasticity Deficits in Neurological and Psychiatric Disorders: Implications for Allosteric Modulators as Novel Therapeutic Strategies

Long-term potentiation (LTP) and long-term depression (LTD) are two distinct forms of synaptic plasticity that have been extensively characterized at the Schaffer collateral-CA1 (SC-CA1) synapse and the mossy fiber (MF)-CA3 synapse within the hippocampus, and are postulated to be the molecular underpinning for several cognitive functions. Deficits in LTP and LTD have been implicated in the pathophysiology of several neurological and psychiatric disorders. Therefore, there has been a large effort focused on developing an understanding of the mechanisms underlying these forms of plasticity and novel therapeutic strategies that improve or rescue these plasticity deficits. Among many other targets, the metabotropic glutamate (mGlu) receptors show promise as novel therapeutic candidates for the treatment of these disorders. Among the eight distinct mGlu receptor subtypes (mGlu1-8), the mGlu1,2,3,5,7 subtypes are expressed throughout the hippocampus and have been shown to play important roles in the regulation of synaptic plasticity in this brain area. However, development of therapeutic agents that target these mGlu receptors has been hampered by a lack of subtype-selective compounds. Recently, discovery of allosteric modulators of mGlu receptors has provided novel ligands that are highly selective for individual mGlu receptor subtypes. The mGlu receptors modulate the multiple forms of synaptic plasticity at both SC-CA1 and MF synapses and allosteric modulators of mGlu receptors have emerged as potential therapeutic agents that may rescue plasticity deficits and improve cognitive function in patients suffering from multiple neurological and psychiatric disorders.
Rapamycin Inhibition of the G1 to S Transition Is Mediated by Effects on Cyclin D1 mRNA and Protein Stability*

The immunosuppressant rapamycin has been shown previously to inhibit the G1/S transition in several cell types by prolonging the G1 phase of the cell cycle. This process appears to be controlled, in part, by the rapamycin-sensitive FK506-binding protein-rapamycin-associated protein-p70 S6 kinase (p70S6k) pathway and the cyclin-dependent kinases (Cdk). We now show that in serum-stimulated NIH 3T3 cells, rapamycin treatment delays the accumulation of cyclin D1 mRNA during progression through G1. Rapamycin also appears to affect stability of the transcript. The combined transcriptional and post-transcriptional effects of the drug ultimately result in decreased levels of cyclin D1 protein. Moreover, degradation of newly synthesized cyclin D1 protein is accelerated by rapamycin, a process prevented by inclusion of the proteasome inhibitor, N-acetyl-Leu-Leu-norleucinal. The overall effect of rapamycin on cyclin D1 leads, in turn, to impaired formation of active complexes with Cdk4, a process which triggers retargeting of the p27Kip1 inhibitor to cyclin E/Cdk2. In view of this novel experimental evidence, we discuss a possible mechanism for the rapamycin-induced cell cycle arrest at the G1/S transition.
Fluoxetine Up-Regulates Bcl-xL Expression in Rat C6 Glioma Cells

Objective To analyze both differentially expressed genes and the Bcl-xL protein expression after acute and chronic treatment with fluoxetine in rat C6 glioma cells. Methods C6 glioma cells were cultured for 24 h or 72 h after treatment with 10 µM fluoxetine, and gene expression patterns were observed using microarray and qRT-PCR. Then, cells were cultured for 6 h, 24 h, 72 h or 96 h after treatment with 10 µM fluoxetine, and the expression of Bcl-xL protein was measured using western blot. Results As determined by microarray, treatment with fluoxetine for 24 h up-regulated 33 genes (including Bcl-xL and NCAM140) and down-regulated 7 genes (including cyclin G-associated kinase). Treatment with fluoxetine for 72 h up-regulated 53 genes (including Gsα and Bcl-xL) and down-regulated 77 genes (including Gαi2 and annexin V). Based on the qRT-PCR results, there was an increase in Gsα mRNA and a decrease in Gαi2 mRNA at 72 h in fluoxetine-treated cells as compared to control, a result that was consistent with microarray. We also observed an increase in Bcl-xL mRNA (both at 24 h and at 72 h) in fluoxetine-treated cells as compared to control, demonstrating a tendency to increase gradually. Bcl-xL protein expression increased as the duration of fluoxetine treatment increased. Conclusion These results suggest that chronic treatment with fluoxetine not only initiates the cAMP pathway through inducing Gsα expression but also induces Bcl-xL expression, thus inhibiting apoptosis.
A Component Testing Approach Supported by a CASE Tool

The lack of information limits component consumers to understand candidate components sufficiently in a way they can check if a given component fulfills its goal. Thus, this work presents an approach to support component testing aiming to reduce the lack of information between component producers and component consumers. Additionally, the approach is covered by a CASE tool integrated in the development environment.
Automatic outlier detection in multibeam bathymetric data using robust LTS estimation

The bathymetric data volumes produced by Multibeam echo-sounders are increasingly large and inevitably contain outliers which must be detected and eliminated. In this paper, an algorithm based on Least Trimmed Squares (LTS) estimator is presented for outlier detection and elimination. LTS estimator is a robust estimator with high Break-down Point (BP). It can efficiently reduce the influences of outliers on surface fitting and obtain a relatively correct seabed trend surface. The difference between the real measured value and the estimated value is then calculated so that the outliers can be detected and removed. The algorithm is tested using both synthetic data and real bathymetric data acquired by multibeam echo-sounders. The results show that the algorithm is robust and able to detect existing clusters and discrete outliers in data sets effectively.
Discerning Affect in Student Discussions

Students’ emotions and attitudes are discernible in messages posted to online question and answer boards. Understanding student sentiment may help instructors identify students with potential course issues, optimize help-seeking, and potentially improve student achievement, as well as identify both positive and negative actions by instructors and provide them with valuable feedback. Towards this end, we present a set of context-independent emotion acts that were used by students in a universitylevel computer science course to express certainty and uncertainty, frustration, and politeness in an online Q&A board and develop viable classification approaches. To explore the potential of sentiment-based profiling, we present a heuristic-driven analysis of thread resolution and detail future research.
Automatic Scoring for Innovativeness of Textual Ideas

Automatic evaluation of text for its innovative quality has been necessitated by the growing trend to organize open innovation contests by different organizations. Such online/offline contests are known to fuel major business benefits to many industries. However, open contests result in a huge number of documents of which only a few may contain potentially interesting and relevant ideas. Usually these entries are manually reviewed and scored by multiple experts. But manual evaluation process not only require a lot of time and effort but are also prone to erroneous judgments due to inter-annotator disagreements. To counter this issue, in this paper, we have proposed a new approach towards detecting novelty or innovativeness of textual ideas from a given collection of ideas. The proposed approach uses information theoretic measures and term relevance to domain to compute document level innovativeness score. We have evaluated the performance of the proposed approach with a real world collection of innovative ideas which were manually scored by experts. We have compared the performance of our proposed model with some of the commonly used baseline approaches that rely on distributional semantics and geometric distances. The result shows that the proposed method outperform the existing baseline models.
The Effects of Ethical Pressure and Power Distance Orientation on Unethical Pro‐Organizational Behavior: The Case of Earnings Management

A multiphase study tested a proposed mediated moderation model for the joint effects of ethical pressure and power distance orientation on accountants’ ethical judgments of earnings management. Results based on a sample of 354 accountants from China indicated that the relationship between ethical pressure and ethical judgments of earnings management is contingent on the accountants’ power distance orientation. That is, the relationship between ethical pressure and ethical judgments of earnings management was stronger for accountants with a high power distance orientation. The results also demonstrated that ethical beliefs in support of the company serve as a mediator for the interaction effect of ethical pressure and power distance orientation on the outcome. These results are discussed in terms of viewing earnings management as a form of unethical pro‐organizational behavior which can be effectively investigated within the framework of the person‐situation interactionist model.
Dopamine D2 receptor functional selectivity as a mechanism of atypical antipsychotic drug action

s representative of this work: Urban JD, Thornley K, Wightman M, and Mailman RB. Pharmacological characterization of the N27-D2L cell line: assessment as a viable cell model for investigating dopaminergic D2L receptor-coupled functions. To be presented at the 46 Annual SOT Meeting at Charlotte, NC, March 2007. Urban JD and Mailman RB. Characterization of the N27 dopaminergic cell line as a model for elucidating the actions of functionally selective dopaminergic ligands. Abstract # 33.21. Presented at the 35 Annual Society for Neuroscience Meeting in Wash DC, November 2005. Urban JD, Gay EA, and Mailman RB. Decreased neurological side-effects with aripiprazole: a result of functional selectivity of the D2 receptor? Abstract # 313. Presented at the 43 Annual SOT Meeting at Baltimore, MD, March 2004. Urban JD, Gay EA, and Mailman RB. Functional selectivity as a mechanism of action of newer atypical antipsychotic drugs. Abstract # 163.4 Presented at the 34 Annual Society for Neuroscience Meeting at San Diego, CA, October 2004.
Leisure Boredom and Substance Use Among High School Students in South Africa

The purpose of this study was to determine the extent of leisure boredom, and investigate the relationship between leisure boredom, substance use and demographic variables among high school students in Cape Town, South Africa. 621 students from 39 high schools selected through a multistage cluster sampling procedure completed a questionnaire which measured substance use and demographic information, and included the Leisure Boredom Scale (LBS). Using generalized estimating equation models, leisure boredom was modeled on the demographic variables, and substance use indicators on leisure boredom. Although no significant association between leisure boredom and substance use was found, girls reported significantly higher leisure boredom than did boys. Also, Black and Colored students reported significantly higher leisure boredom than White students. This finding may be partly attributed to socio-economic status, as race is still a strong indicator for socio-economic status in South Africa. The findings imply that there is a need for leisure education programs for adolescents which are developmentally and socio-culturally appropriate.
Designs and Experiments of a Novel Radial Line Slot Antenna for High-Power Microwave Application

A radial line slot antenna (RLSA) is a nonresonant multimode waveguide slotted array. To improve the power handing capacity, we design a radial line slow wave structure which replaces a traditional dielectric sheet. At the same time, the structure of the radiator unit is redesigned and optimised. This high-power microwave (HPM) RLSA is fed from a double-layered radial line waveguide to realize the directional radiation of high-power microwave. However, the slots spirally arrayed for circular polarization give rise to serious reflection in higher order modes, which disturbs the normal antenna operation. A reflection cancelling slot is added to the conventional one and the antenna return-loss is effectively improved. An antenna operating at 9.42 GHz was designed with a length of 15 cm and an aperture radius of 27 cm. Numerical simulation results show that the calculated aperture efficiency reaches 44.8%, the reflectance is less than -20 dB, the radiation efficiency is more than 99%. Experimental measurements are accomplished for the prototype. In the range of 9.30-9.45 GHz, the reflection of the antenna is below -10 dB. The antenna gain reaches 29.0 dBi, and the axial ratio is below 1.6 dB. In addition, the high-power experiment proves that this antenna has a power-handing capacity of more than 1 GW.