Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Mechanisms of Liver Carcinogenesis in the Mdr2-Knockout Mice

Mouse models of hepatocellular carcinoma (HCC) simulate specific subgroups of human HCC. We investigated hepatocarcinogenesis in Mdr2-knockout (Mdr2-KO) mice, a model of inflammation-associated HCC, using gene expression profiling and immunohistochemical analyses. Gene expression profiling showed that although Mdr2-KO mice differ from other published murine HCC models, they share several important deregulated pathways and many coordinately differentially expressed genes with human HCC data sets. Analysis of genome positions of differentially expressed genes in liver tumors revealed a prolonged region of down-regulated genes on murine chromosome 8 in three of the six analyzed tumor samples. This region is syntenic to human chromosomal regions that are frequently deleted in human HCC and harbor multiple tumor suppressor genes. Real-time reverse transcription-PCR analysis of 16 tumor samples confirmed down-regulation of several tumor suppressors in most tumors. We show that in the aged Mdr2-KO mice, cyclin D1 nuclear level is increased in dysplastic hepatocytes that do not form nodules; however, it is decreased in most dysplastic nodules and in liver tumors. We found that this decrease is mostly at the protein, rather than the mRNA, level. These findings raise the question on the role of cyclin D1 at early stages of hepatocarcinogenesis in the Mdr2-KO HCC model. Furthermore, we show that most liver tumors in Mdr2-KO mice were characterized by the absence of β-catenin activation. In conclusion, the Mdr2-KO mouse may serve as a model for β-catenin–negative subgroup of human HCCs characterized by low nuclear cyclin D1 levels in tumor cells and by down-regulation of multiple tumor suppressor genes. (Mol Cancer Res 2007;5(11):1159–70)
Nucleosome dynamics: HMGB1 relaxes canonical nucleosome structure to facilitate estrogen receptor binding

High mobility group protein 1 (HMGB1) interacts with DNA and chromatin to influence the regulation of transcription, DNA repair and recombination. We show that HMGB1 alters the structure and stability of the canonical nucleosome (N) in a nonenzymatic, ATP-independent manner. Although estrogen receptor (ER) does not bind to its consensus estrogen response element within a nucleosome, HMGB1 restructures the nucleosome to facilitate strong ER binding. The isolated HMGB1-restructured nucleosomes (N′ and N″) remain stable and exhibit characteristics distinctly different from the canonical nucleosome. These findings complement previous studies that showed (i) HMGB1 stimulates in vivo transcriptional activation at estrogen response elements and (ii) knock down of HMGB1 expression by siRNA precipitously reduced transcriptional activation. The findings indicate that one aspect of the mechanism of HMGB1 action involves a restructuring of the nucleosome that appears to relax structural constraints within the nucleosome.
Experimental Evolution of Pseudomonas fluorescens in Simple and Complex Environments

In complex environments that contain several substitutable resources, lineages may become specialized to consume only one or a few of them. Here we investigate the importance of environmental complexity in determining the evolution of niche width over ∼900 generations in a chemically defined experimental system. We propagated 120 replicate lines of the bacterium Pseudomonas fluorescens in environments of different complexity by using between one and eight carbon substrates in each environment. Genotypes from populations selected in complex environments evolved greater mean and variance in fitness than those from populations selected in simple environments. Thus, lineages were able to adapt to several substrates simultaneously without any appreciable loss of function with respect to other substrates present in the media. There was greater genetic and genotype‐by‐environment interaction variance for fitness within populations selected in complex environments. It is likely that genetic variance in populations grown on complex media was maintained because the identity of the fittest genotype varied among carbon substrates. Our results suggest that evolution in complex environments will result neither in narrow specialists nor in complete generalists but instead in overlapping imperfect generalists, each of which has become adapted to a certain range of substrates but not to all.
Privacy, Publicity, and Accountability of Self‐Presentation in an On‐Line Discussion Group*

Although the anonymous condition of on-line interaction seems to provide space for the experiment of decentered, fluid, and multiple forms of identity, the disembodied on-line identity often entails the fallout of accountability of self-presentation. This article explores the nature of self-presentation in cyberspace by conducting a case study of an on-line discussion group. Specifically, it deals with the issue of disembodiment and accountability of on-line identity in a close connection to the feature of the obliteration of the public/private boundary in the group. This study inquires into the following questions: "What techniques, if any, do members of the group employ to conceal their identity information? "; "Under what circumstances do members voluntarily disclose their identity information? "; "How do participants probe others' identity cues and thus construct pattern knowledge about them? "; and "How should differences/similarities between on-line self-presentation and face-to-face identity styles be addressed? " In doing so, this article, on the one hand, tries to integrate the dynamics of participants' active "identity probing" as an important interaction dimension to the study of on-line self-presentation that has so far heavily worked on the processes of identity concealment and self-disclosure. On the other, referring to literatures on identity styles in off-line settings, it addresses similarities of and differences between patterns of on-line/off-line self-presentation.
Mining Challenge 2010: FreeBSD, GNOME Desktop and Debian/Ubuntu

In a young field, such as Mining Software Repositories (MSR), there is always a call for benchmarks so that researchers can compare their results against others. Thus in order to explore and discover the breadth of MSR research, the MSR community has banded together behind the MSR Mining Challenge. The mining challenge allows researchers to demonstrate current working techniques against a common set of repositories or datasets with the express purpose of mining interesting facts from these datasets and then comparing these results against the results from other researchers. This year, 2010, the MSR Mining Challenge has expanded the size of its underlying dataset to include the version control, bug tracker, and mailinglists of the following software distributions and projects: FreeBSD, GNOME Desktop and Debian/Ubuntu. Researchers are asked to look beyond the boundaries of a project and investigate the relationship between the evolution of various programs contained within these software ecosystems. 9 general challenge submissions were submitted, 6 were accepted with a 66% acceptance rate.
Towards an Adaptive Deployment and Configuration Framework for Component-based Distributed Systems

Software frameworks that support the deployment and configuration (D&C) of large-scale component-based distributed real-time and embedded (DRE) systems must often adapt their behavior at runtime to accommodate changing requirements and environments. For example, a D&C framework may need to interact with new deployment targets to interact and integrate with either new or legacy systems that use different communication or deployment mechanisms. Moreover, the D&C framework itself may require customization to satisfy domain requirements, e.g., to change the behavior of error handling or event logging. This paper describes the shortcomings of the OMG D&C standard in terms of its ability to support heterogeneity and adapt its behavior in response to changing requirements. We also show how our Locality-Enabled Deployment and Configuration Engine (LE-DAnCE) provides novel approaches for addressing these limitations by enabling heterogeneous deployments, customizable behavior, and runtime adaptation of the deployment and configuration frameworks for component-based DRE systems.
A phase I study of intravenous TZT-1027 administered on day 1 and day 8 of a three-weekly cycle in combination with carboplatin given on day 1 alone in patients with advanced solid tumours.

BACKGROUND TZT-1027 is a tubulin-binding drug and synthetic derivative of dolastatin-10 with cytotoxic and antivascular activity in vitro and in vivo. Studies have demonstrated anti-tumour activity in several tumour types. METHODS Patients were treated with escalating doses of TZT-1027 and carboplatin at doses from 1.6 to 2.0 mg/m2 and AUC 4 and 5 respectively. For pharmacokinetic analysis, plasma sampling was done during the first course using a high-performance liquid chromatographic assay. RESULTS 14 patients received a total of 55 cycles at three dose levels. Dose limiting toxicities (DLTs) were first observed with 1.6 mg/m2 TZT-1027 and carboplatin AUC 5; 1 patient had grade 4 neutropenia and a delay in day 8 treatment occurred in two patients (gr 2 fatigue, gr 3 diarrhoea). At TZT-1027 2 mg/m2 and carboplatin AUC 5, one patient experienced grade 3 paralytic ileus. The most frequent toxicities were neutropenia, anaemia, fatigue, constipation, infection and vomiting. Peripheral neuropathy was reported in 36% of patients. One patient (pancreatic adenocarcinoma) achieved a partial response lasting 181 days. Pharmacokinetic analysis did not demonstrate any interaction between TZT-1027 and carboplatin. CONCLUSIONS The recommended phase II dose is TZT-1027 1.6 mg/m2 and carboplatin AUC 5. No evidence of a PK interaction between these agents was observed.
Psychosocial Treatments for Individuals with Schizophrenia and Tobacco Dependence

ABSTRACT While the underutilization of psychosocial treatments for tobacco dependence may be problematic in general, it is especially problematic in smokers with schizophrenia who may need more assistance than those in the general population. Psychosocial approaches are important for motivating ambivalent smokers with schizophrenia to make a quit attempt (i.e., via motivational interviewing) and for providing the smoker with the tools necessary for a successful quit attempt. This paper discusses psychosocial treatment approaches available to the general population, those used in published clinical trials of tobacco dependence for smokers with schizophrenia, and an ongoing clinical trial comparing a high vs. moderately intensive psychosocial treatment for tobacco dependence in smokers with schizophrenia. We also discuss a new consumer advocacy program for smokers with schizophrenia and make recommendations for using psychosocial approaches to treat tobacco dependence in smokers with schizophrenia.
A Puristic Approach for Joint Dependency Parsing and Semantic Role Labeling

We present a puristic approach for combining dependency parsing and semantic role labeling. In a first step, a data-driven strict incremental deterministic parser is used to compute a single syntactic dependency structure using a MEM trained on the syntactic part of the CoNLL 2008 training corpus. In a second step, a cascade of MEMs is used to identify predicates, and, for each found predicate, to identify its arguments and their types. All the MEMs used here are trained only with labeled data from the CoNLL 2008 corpus. We participated in the closed challenge, and obtained a labeled macro F1 for WSJ+Brown of 19.93 (20.13 on WSJ only, 18.14 on Brown). For the syntactic dependencies we got similar bad results (WSJ+Brown=16.25, WSJ= 16.22, Brown=16.47), as well as for the semantic dependencies (WSJ+Brown=22.36, WSJ=22.86, Brown=17.94). The current results of the experiments suggest that our risky puristic approach of following a strict incremental parsing approach together with the closed data-driven perspective of a joined syntactic and semantic labeling was actually too optimistic and eventually too puristic.
A Comparative Investigation of Morphological Language Modeling for the Languages of the European Union

We investigate a language model that combines morphological and shape features with a Kneser-Ney model and test it in a large crosslingual study of European languages. Even though the model is generic and we use the same architecture and features for all languages, the model achieves reductions in perplexity for all 21 languages represented in the Europarl corpus, ranging from 3% to 11%. We show that almost all of this perplexity reduction can be achieved by identifying suffixes by frequency.
DSpam: Defending Against Spam in Tagging Systems via Users' Reliability

Resisting spam in tagging system is very challenging. This paper presents DSpam, a novel spam-resistant tagging system which can significantly diminish spam in tag search results with users’ reliabilities. DSpam client groups other users into unfamiliar users and interacted users according to the fact whether the client has interacted with such users. For an unfamiliar user, the client computes his reliability by tagging behavior-based mechanism which reflects correlation of annotations between them. For an interacted user, the reliability includes two parts: feedback-based reliability, which indicates direct interactions between that user and the client, and recommendation reliability, which indicates the evaluation about that user from the client’s friends. The client ranks search result with the average reliabilities of himself with respect to annotators of each result. Experimental results show DSpam can effectively resist tag spam and work better than existing tag search schemes.
Proposing a standardized method for evaluating patient report of the intensity of dyspnea during exercise testing in COPD

Background Measuring dyspnea intensity associated with exercise provides insights into dyspnea-limited exercise capacity, and has been used to evaluate treatment outcomes for chronic obstructive pulmonary disease (COPD). Three patient-reported outcome scales commonly cited for rating dyspnea during exercise are the modified Borg scale (MBS), numerical rating scale for dyspnea (NRS-D), and visual analogue scale for dyspnea (VAS-D). Various versions of each scale were found. Our objective was to evaluate the content validity of scales commonly used in COPD studies, to explore their ability to capture patients’ experiences of dyspnea during exercise, and to evaluate a standardized version of the MBS. Methods A two-stage procedure was used, with each stage involving one-on-one interviews with COPD patients who had recently completed a clinic-based exercise event on a treadmill or cycle ergometer. An open-ended elicitation interview technique was used to understand patients’ experiences of exercise-induced dyspnea, followed by patients completing the three scales. The cognitive interviewing component of the study involved specific questions to evaluate the patients’ perspectives of the content and format of the scales. Results from Stage 1 were used to develop a standardized version of the MBS, which was then subjected to further content validity assessment during Stage 2. Results Thirteen patients participated in the two-stage process (n = 6; n = 7). Mean forced expiratory volume in 1 second (FEV1) percent predicted was 40%, mean age 57 years, and 54% were male. Participants used a variety of terms to describe the intensity and variability of exercise-induced dyspnea. Subjects understood the instructions and format of the standardized MBS, and were able to easily select a response to report the level of dyspnea associated with their recent standardized exercise. Conclusion This study provides initial evidence in support of using a standardized version of the MBS version for quantifying dyspnea intensity associated with exercise in patients with COPD.
An In-Line Waveguide-to-Microstrip Transition Using Radial-Shaped Probe

In this letter, an in-line waveguide-to-microstrip transition at Ka-band is presented. It utilizes a radial-shaped probe a quarter-wavelength away from the waveguide short-back, which is also used as a support for the microstrip substrate, to terminate the TE10 mode of the standard waveguide. This printed structure is easy to fabricate and convenient to be installed in the waveguide cavity with a split-block configuration. A test module at Ka-band is designed and fabricated. It provides a return loss better than 10 dB from 26.5 to 38.5 GHz and an insertion loss of 1.2 to 2 dB within a wide frequency range from 26.5 to 36.2 GHz with a low cost, easy to fabricate printed structure. The measured results show good agreement with the simulated ones.
Transcriptome Sequencing Reveals the Character of Incomplete Dosage Compensation across Multiple Tissues in Flycatchers

Sex chromosome divergence, which follows the cessation of recombination and degeneration of the sex-limited chromosome, can cause a reduction in expression level for sex-linked genes in the heterozygous sex, unless some mechanisms of dosage compensation develops to counter the reduction in gene dose. Because large-scale perturbations in expression levels arising from changes in gene dose might have strong deleterious effects, the evolutionary response should be strong. However, in birds and in at least some other female heterogametic organisms, wholesale sex chromosome dosage compensation does not seem to occur. Using RNA-seq of multiple tissues and individuals, we investigated male and female expression levels of Z-linked and autosomal genes in the collared flycatcher, a bird for which a draft genome sequence recently has been reported. We found that male expression of Z-linked genes was on average 50% higher than female expression, although there was considerable variation in the male-to-female ratio among genes. The ratio for individual genes was well correlated among tissues and there was also a correlation in the extent of compensation between flycatcher and chicken orthologs. The relative excess of male expression was positively correlated with expression breadth, expression level, and number of interacting proteins (protein connectivity), and negatively correlated with variance in expression. These observations lead to a model of compensation occurring on a gene-by-gene basis, supported by an absence of clustering of genes on the Z chromosome with respect to the extent of compensation. Equal mean expression level of autosomal and Z-linked genes in males, and 50% higher expression of autosomal than Z-linked genes in females, is compatible with that partial compensation is achieved by hypertranscription from females’ single Z chromosome. A comparison with male-to-female expression ratios in orthologous Z-linked genes of ostriches, where Z–W recombination still occurs, suggests that male-biased expression of Z-linked genes is a derived trait after avian sex chromosome divergence.
User Acceptance of Recommender Systems: Influence of the Preference Elicitation Algorithm

We conducted a user study evaluating two preference elicitation approaches for collaborative filtering recommender systems: a basic KNN algorithm and a context aware algorithm. Using the technology acceptance model (TAM) as theoretical model, we considered different factors affecting the perceived usefulness, perceived ease of use and attitude towards using the recommender system. We found that the underlying algorithm can affect in different ways the user perception of the system as a whole. Although the system interface was the same for all users, users found the context aware system easier to use, with more attractive recommendations that were better adapted to their mood and tastes. Users using the context aware system also showed a better acceptance of the fact that the system was able to learn about their preferences and expressed a stronger intention to use the system again.
“This Is Called Free-Falling Theory not Culture Shock!”: A Narrative Inquiry on Second Language Socialization

Grounded in the framework of second language socialization, this study explores the identity (re)construction of Erol, a Turkish doctoral student in the United States. Drawn from a larger corpus collected for a longitudinal, mixed-method research, the data for this study came from autobiographies, journal entries, and semistructured interviews. Based on a synthesis of inductive-thematic analysis (Boyatzis, 1998), as well as deductive approaches through the use of three sensitizing concepts—investment (Norton, 1995), cultural capital (Bourdieu, 1977), and audibility (Miller, 2003)—Erol's social identity (re)construction was marked with struggle: first, to gain social networks and, second, to be recognized within the target language community. Erol's story, while providing evidence for the role of affective and socially structured variables in enabling language learners’ access to social interactions, also draws attention to the need for more research at the discourse level to explore how power relations within speech communities influence the nature of interaction between international students and the host culture.
Semantic priming in anomic aphasia: a focused investigation using cross-modal methodology

Background: Semantic priming in individuals with anomic aphasia has never been the primary focus of an investigation. To date, one study investigated the effects of semantic priming in individuals with fluent aphasia (including anomic aphasia), revealing an inconsistency in semantic priming in the anomic group. Parallels from Broca’s aphasia and Wernicke’s aphasia literature may be drawn. However, due to the heterogeneity of anomic aphasia, a focused investigation was necessary. Aims: Semantic priming effects were investigated using a cross-modal pairwise paradigm. It was hypothesised that participants with anomic aphasia would demonstrate priming patterns at a stimulus onset asynchrony (SOA) of 500 ms with slower overall reaction times (RTs) than the control participants. It was further hypothesised that the participants with anomic aphasia might show less inhibition effects than the control participants. Methods & Procedures: Participants with anomic aphasia (n = 11) and healthy control participants (n = 16) completed a lexical decision task where prime–target pairs were present in equal proportions (related, unrelated, and nonwords). A neutral prime condition was also incorporated. Using a cross-modal pairwise paradigm, participants heard a spoken word 500 ms later, a written word appeared on screen (for 4000 ms). Participants were required to make a decision as to whether the written word was real, and RTs were recorded. Outcomes & Results: Linear mixed model analysis was undertaken and revealed no significant two-way interaction effect, indicating both groups showed priming patterns. A main effect of group was evident, showing faster RTs by the control participant group, confirming our hypothesis that people with anomic aphasia primed at an SOA of 500 ms in a similar manner to the control participants, with slower RTs. Conclusions: Semantic priming effects were present in anomic aphasia at relatively short SOAs and may be contributed to by automatic processes. Several parameters are proposed that should be adopted for further investigation into semantic priming in anomic aphasia including electrophysiological measures and manipulation of SOAs and relatedness proportions (RPs) to more precisely measure the effects of controlled versus automatic processes. Such investigation has the potential to inform new assessment and management techniques.