Miracle-dz/UniFAR-FTUs huggingface dataset:
Krüppel-like factor 2 suppresses human gastric tumorigenesis through inhibiting PTEN/AKT signaling

Krüppel-like factors (KLFs) are a large family of DNA-binding transcriptional regulators that affect basic cellular processes such as growth, survival, migration and differentiation and serve a complicated function in cancers. KLF2, one member of the KLF family, is dysregulated in many tumors. However, the specific role of KLF2 in human gastric tumorigenesis is unknown. Here we show that the expression of KLF2 protein was lower in gastric tumors when compared with adjacent normal tissue. Moreover, downregulated KLF2 expression in primary gastric tumor was closely correlated with patients’ survival. Various cell experiments showed that ectopic KLF2 expression suppressed the proliferation, migration and invasion of gastric cancer cells. Moreover, KLF2 overexpression remarkably enhanced cell apoptosis and induced cell cycle arrest. Impaired expression of KLF2 markedly promoted cell growth in vitro and significantly expanded tumor size in vivo. Mechanically, the mRNA and protein level of PTEN was reduced in KLF2 deficient cells and xenograft tumors, suggesting that PTEN/AKT signaling was involved in the gastric tumor inhibitory effect of KLF2. Administration of AKT inhibitor AZD5363 or Insulin-like growth factor-1 (IGF-1) in KLF2 knockdown or ectopic expression cell lines, respectively, substantially reversed the proliferation phenotype. Collectively, our findings provide clinical evidence and a potential mechanism supporting that KLF2 suppresses human gastric tumorigenesis through inhibiting the PTEN/AKT axis.
Studying Environmental Influence on Motor Development in Children

There is a good argument that in order to truly understand the influences that shape child motor development, one must consider environmental influences that reflect the multilevel ecological contexts that interact with the changing biological characteristics of the child. Although there are theories typically associated with motor development that mention environmental influence (e.g., constraints, affordances), none provide the comprehensive framework comparable to the works of Bronfenbrenner (1979, 2005). With this paper, we address the need for environmental considerations, highlight Bronfenbrenner’s work and application to the field of motor development, and provide examples for research using two contemporary themes.
Community, Conversation and Collaboration: Experiences gained through Working on Postgraduate Online Distance Education Programmes

This paper takes the position that community, collaboration and conversation are essential elements of the success of the MA ICT and Education at Leeds. We feel that successful design and delivery of an e-learning programme not only requires subject matter expertise and/or technical skills, but that pedagogical, information and communication skills to manage and facilitate online learning are also needed. The discussion is largely focussed on the merits of synchronous for the MA ICT in Education programme offered by the University of Leeds and this is compared to previous experiences of providing asynchronous communication tools for postgraduate distance education students.
Rebutting Arrow and Lind: why governments should use market rates for discounting

The radical proposition of Arrow and Lind (1970) – that governments should use risk-free rates instead of market rates to discount their risky investments – can best be understood by first considering the work in its historical context. During the late 1960s and early 1970s, a debate was raging between the leading economists of the time about the cost of risk to the government, and related, the identification of the social discount rate. Recent advances in general equilibrium theory (notably, Arrow & Debreu, 1954; Debreu, 1959) allowed for more general welfare analyses of policy than had been undertaken previously; underscored the benefits of risk-sharing as well as the aggregate limits on risk-sharing; and clarified the role of market prices in aggregating the risk preferences of society. Such analyses also highlighted the potentially salutary role for governments in improving risksharing when markets are incomplete. On one side of the debate were authors who took the position that governments should rely on market prices in evaluating the cost of investments. Diamond (1967) analyzed an economy with technology risk and a stock market. Perhaps not surprisingly, he concluded that if markets are sufficiently complete for stock prices to reflect the social cost of risk, then those prices are also relevant to the government in evaluating its investment policy. Hirshleifer (1964, 1966) reached similar conclusions and argued forcefully for the use of market prices by governments. Other leading economists of the time advocated the position that was subsequently formalized in Arrow and Lind. Samuelson and Vickrey (in Jorgenson et al., 1964) argued that because of the large and diversified portfolio held by the government, the marginal return from public investment overall is virtually risk-free, and hence should be evaluated at the risk-free rate rather than the higher market rate demanded by less diversified investors. (The government’s own borrowing rate is usually taken as a proxy for the risk-free rate.) The specialness of the assumptions required to formalize the idea that the cost of market risk is irrelevant to the government – in particular, that there is no aggregate uncertainty affecting the value of government investments – was acknowledged by Arrow and Lind: ‘The results.depend on returns from a given public investment being independent of other components of national income’ (p. 373). Arrow and Lind defended that assumption with the assertion that correlated risk is likely to be insignificant for many government investments.
Short article: Is verbal–spatial binding in working memory impaired by a concurrent memory load?

Binding processes play a critical role in memory. We investigated whether the binding of (visually presented) verbal and spatial (locations) information involves general attentional resources, as stipulated in the revised working memory model, by comparing measures of binding in the presence and absence of a concurrent memory load. Using an adaptation of a probe recognition task contrasting performance between intact and recombined conditions, we found that the concurrent retention of a sequence of three pure tones eliminated verbal–spatial binding. The present study constitutes the first to directly measure the impact of a concurrent memory load on verbal–spatial binding and suggests that such binding may indeed recruit attentional resources, consistent with some recent findings in the visual–spatial binding literature.
Image classification with limited training data and class ambiguity

Modern image classification methods are based on supervised learning algorithms that require labeled training data. However, only a limited amount of annotated data may be available in certain applications due to scarcity of the data itself or high costs associated with human annotation. Introduction of additional information and structural constraints can help improve the performance of a learning algorithm. In this thesis, we study the framework of learning using privileged information and demonstrate its relation to learning with instance weights. We also consider multitask feature learning and develop an efficient dual optimization scheme that is particularly well suited to problems with high dimensional image descriptors. Scaling annotation to a large number of image categories leads to the problem of class ambiguity where clear distinction between the classes is no longer possible. Many real world images are naturally multilabel yet the existing annotation might only contain a single label. In this thesis, we propose and analyze a number of loss functions that allow for a certain tolerance in top k predictions of a learner. Our results indicate consistent improvements over the standard loss functions that put more penalty on the first incorrect prediction compared to the proposed losses. All proposed learning methods are complemented with efficient optimization schemes that are based on stochastic dual coordinate ascent for convex problems and on gradient descent for nonconvex formulations.
Dielectric Breakdown of $\hbox{Al}_{2}\hbox{O}_{3}/ \hbox{HfO}_{2}$ Bi-Layer Gate Dielectric

We investigate the dielectric breakdown of aluminum oxide (Al<sub>2</sub>O<sub>3</sub>) interfacial layers compared with SiO<sub>2</sub> used in the high- k gate dielectric stacks. We predict the maximum operating voltage for a ten-year lifetime, using extracted values of Weibull β, voltage power law exponent (n), and breakdown voltage. We show that the Al<sub>2</sub>O<sub>3</sub> interface layer reliability is sufficient for it to be considered as a replacement for SiO<sub>2</sub>.
Correlations Between Musical Descriptors and Emotions Recognized in Beethoven’s Eroica

Investigations on music and emotion have identified broad musical elements that influence emotions recognized by listeners, such as timbre, rhythm, melody, and harmony. Not many studies have studied the correlation between quantifiable musical descriptors and their associated emotions; furthermore, only few studies have focused on how listeners’ demographic and musical backgrounds influence the emotion they recognize. In this preliminary study, participants rated how strongly they recognized the six GEMS emotions (transcendence, peacefulness, power, joyful activation, tension, and sadness) while listening to excerpts from Beethoven’s Eroica. Musical descriptors (loudness, brightness, noisiness, tempo/rhythm, harmony, and timbre) were also extracted from each excerpt. Results indicate significant correlations between emotional ratings and musical descriptors, notably positive correlations between key clarity and peacefulness/joyful activation ratings, and negative correlations between key clarity and tension/sadness ratings. Key clarity refers to the key strength associated to the best key candidate; as such, these results suggest that listeners recognize positive emotions in music with a straightforward key, whereas listeners recognize negative emotions in music with a less clear sense of key. The second part of the study computed correlations between demographics and emotional ratings, to determine whether people of similar demographic and musical backgrounds recognized similar emotions. The results indicate that naive listeners (i.e. younger subjects, and subjects with less frequent exposure to classical music) experienced more similar emotions from the same musical excerpts than did other subjects. Our findings contribute to developing a quantitative understanding of how musical descriptors, and listeners’ backgrounds, correlate with emotions recognized by listeners.
Türk işaret dilinde soru: Kaş hareketlerinin dilsel çözümlemesi

Bu arastirmada, Turk Isaret Dili soru tumcelerinde kas hareketinin dilsel rolu incelenmistir. Calismada ayrica, soru tumcelerinin gorunumunde onemli role sahip oldugu dusunulen Turk Isaret Dilinde bilgi yapisinin bicimlenisi ve dilsel gerceklesimi arastirilmistir. Evet/hayir soru tumceleri, ne soru tumceleri ve bildiri tumcelerindeki kas yuksekligini, niceliksel acidan olcmek amaciyla toplam 120 tumceden elde edilen 883 fotograf uzerinde 2700’den fazla olcum yapilmistir. Her bir tumce icin minimum, maksimum ve ortalama kas yuksekligi olculmustur. Sonuclar gostermistir ki, Turk Isaret Dili, soru tumcesi turlerini birbirinden ayirmak icin kas yuksekligini kullanmaktadir. Evet/hayir soru tumcesi kas yuksekligi, bildiri tumceleri ve ne soru tumcelerinden yuksek, ne soru tumcesi kas yuksekligi ise hem bildiri hem de evet/hayir soru tumcelerinden dusuktur. Bunun yani sira, soru tumcelerinde el disi isaret zorunlu olarak tum tumcede gorulmektedir. Bu arastirmada, ayrica, Turk Isaret Dili bilgi yapisinin konu-yourum, bilgi odagi, empatik odak ve konudan olusan dortlu bir bolumlenis icerdigi ve Lillo-Martin ve Quadros (2008)'de onerilen bilgi yapisi modelinin Turk Isaret Dilinde bilgi yapisinin aciklanmasinda kullanilabilecegi de aciga cikmistir.Abstract In this study, linguistic role of the eyebrows movement in interrogative sentences of Turkish Sign Language (TID) was examined. This study also scrutinize the formation of information structure in Turkish Sign Language and its linguistic realization which are thought to play important role in interrogative means. To investigate eyebrow height in yes/no questions, wh-questions and statements, more than 2700 quantitive measurements was done over 883 pictures recorded from a total of 120 signed sentences. Minimum, maximum and mean eyebrow height for each sentence was examined. The findings show that TID use eyebrow height to distinguish between question types. Eyebrow height in yes/no questions is higher than both statements and wh-questions; Eyebrow height in wh-questions is lower than both statements and yes/no questions. Furthermore, in interrogative sentences, nonmanual marking spreads obligatorily over the entire sentence. This study also reveals that information structure in Turkish Sign Language is four-partite, which has topic-comment, information focus, emphatic focus and topic, and that information structure model offered by Lillo-Martin and Quadros (2008) can be used to unfold information structure in Turkish Sign Language.
Diagnostic Evaluation of HER-2 as a Molecular Target: An Assessment of Accuracy and Reproducibility of Laboratory Testing in Large, Prospective, Randomized Clinical Trials

Purpose: To critically assess the accuracy and reproducibility of human epidermal growth factor receptor type 2 (HER-2) testing in outside/local community-based hospitals versus two centralized reference laboratories and its effect on selection of women for trastuzumab (Herceptin)–based clinical trials. Experimental Design: Breast cancer specimens from 2,600 women were prospectively evaluated by fluorescence in situ hybridization (FISH) for entry into Breast Cancer International Research Group (BCIRG) clinical trials for HER-2-directed therapies. Results:HER-2 gene amplification by FISH was observed in 657 of the 2,502 (26%) breast cancers successfully analyzed. Among 2,243 breast cancers with central laboratory immunohistochemistry (10H8-IHC) analysis, 504 (22.54%) showed overexpression (2+ or 3+). Outside/local laboratories assessed HER-2 status by immunohistochemistry in 1,536 of these cases and by FISH in 131 cases. Overall, the HER-2 alteration status determined by outside/local immunohistochemistry showed a 79% agreement rate [κ statistic, 0.56; 95% confidence interval (95% CI), 0.52-0.60], with FISH done by the central laboratories. The agreement rate comparing BCIRG central laboratory 10H8-IHC and outside/local laboratory immunohistochemistry was 77.5% (κ statistic, 0.51; 95% CI, 0.46-0.55). Finally, HER-2 status, determined by unspecified FISH assay methods at outside/local laboratories, showed a 92% agreement rate (κ statistic, 0.83; 95% CI, 0.73-0.93), with FISH done at the BCIRG central laboratories. Conclusions: Compared with the HER-2 status determined at centralized BCIRG reference laboratories, these results indicate superiority of FISH to accurately and reproducibly assess tumors for the HER-2 alteration at outside/local laboratories for entry to clinical trials.
Mechanical isolation of the inner cell mass is effective in derivation of new human embryonic stem cell lines.

BACKGROUND For clinical grade human embryonic stem cell (hESC) lines, a robust derivation system without any substances having animal origin would be required. We have gradually improved our hESC derivations. Human skin fibroblasts were used as feeder cells in derivation of all our 25 permanent fully characterized hESC lines. In the first four derivations, fetal calf serum was used as a supplement in the medium, thereafter, serum replacement medium was used. Immunosurgery generally used for isolation of the inner cell mass (ICM) still involves animal serum and complement. METHODS We developed a practical mechanical isolation method for the ICM. Two flexible metal needles with sharpened tips, 0.125 mm in diameter, were used to open the zona pellucida and extract the ICM under a stereomicroscope. Immunohistochemical and karyotype characterization of the new hESC lines was carried out, and pluripotency was tested in vitro (immunocytochemistry and RT-PCR) and in vivo (teratoma growth). RESULTS Five hESC lines were obtained from 19 supernumerary blastocysts collected in 2005-2006 (26%), whereas in similar conditions, we obtained 16 lines from 100 blastocysts (16%) using immunosurgery in 2003-2005. The new lines had a normal karyotype and tissues originating from the three embryonic germ cell layers were present. CONCLUSIONS Mechanical isolation of the ICM proved to be an effective way to derive new hESC lines. The technique is fast, does not require any extra investment and the xeno-components of immunosurgery could be avoided.
Human Neuroscience

The developmental distinction between different aspects of recognition memory may refl ect two dissociable mnemonic processes; recollection , that includes specifi c knowledge of the details of the event, and familiarity, that may include less contextual details (Jacoby et al., 1993; Yonelinas, 1999). In a functional neuroimaging study of memory encoding for scenes in 8 to 24-year olds, development of successful memory encoding was associated with increased activation in PFC regions that were specifi cally associated with recollection (but not familiarity) for scenes (Ofen et al., 2007). In contrast, MTL regions were similarly activated across age. These fi ndings suggested that the protracted development of recollection relative to familiarity could refl ect protracted maturation of PFC relative to MTL functions supporting memory formation. The lack of developmental changes for activations in the MTL in our previous study suggested that memory processes served by MTL are mature by the age of 8 years. This conclusion, however, contradicts other evidence that implicates prolonged maturation of MTL subregions. First, memory for high-level visual stimuli such as natural scenes and faces grows from childhood through adolescence into young adulthood (Diamond and Carey, 1977; Mandler and Robinson, 1978), and this development of memory ability has been associated with the development of cortical areas that are specialized for visual perception of scenes and faces (Golarai et al., 2007). Specifi cally, functionally -defi ned scene-selective parahippocampal cortex known as the 'parahippocampal place area' or PPA (Epstein and Kanwisher, 1998) grows in size from childhood through adulthood, and this
Treatment and Prevention of Osteoarthritis through Exercise and Sports

Osteoarthritis (OA) is a degenerative joint disease with a high prevalence among older people. To date, the pathogenesis of the disease and the link between muscle function and OA is not entirely understood. As there is no known cure for OA, current research focuses on prevention and symptomatic treatment of the disorder. Recent research has indicated that muscle weakness precedes the onset of OA symptoms. Furthermore, several studies show a beneficial effect of land-based aerobic and strengthening exercises on pain relief and joint function. Therefore, current research focuses on the possibility to employ exercise and sports in the prevention and treatment of OA.
The acceleration of the propagation phase of thrombin generation in patients with steady-state sickle cell disease is associated with circulating erythrocyte-derived microparticles

Summary Sickle cell disease (SCD) is linked to hypercoagulability and is characterised by high concentrations of erythrocyte-derived microparticles (Ed-MPs). However, the impact of procoagulant cell-derived microparticles on the thrombin generation process remains unclear. We analysed the alterations of each phase of thrombin generation (TG) in relation to the concentration of erythrocyte- or platelet-derived microparticles (Ed-MPs and Pd-MPs) in a cohort of patients with steady-state SCD. We studied 92 steady-state SCD patients, 19 of which were under treatment with hydroxyurea, and 30 healthy age- and sex-matched individuals. TG was assessed by calibrated automated thrombogram. Ed-MP and Pd-MP expressing or not phosphatidylserine (PS) were determined by means of flow cytometry. Procoagulant phospholipid-dependent activity in the plasma was evaluated by the Procoag-PPL assay. Levels of thrombomodulin and haemoglobin in the plasma as well as red blood cell and reticulocyte counts were measured. SCD patients, independently of the administration of hydroxyurea, were marked by a significant acceleration in the propagation phase of TG which correlated with the Ed-MP/PS+ concentration. TG was significantly attenuated in hydroxyurea-treated patients. In conclusion, the acceleration of the propagation phase of TG, driven by Ed-MP/PS+, is a major functional alteration in blood coagulation in patients with steady-state SCD. Treatment with hydroxyurea, in addition to the regulation of haemolysis, lowers Ed-MPs and attenuates thrombin generation. The thrombogram could be a useful tool for the diagnosis of hypercoagulability and optimisation of the treatment in patients with SCD.
Impairment by Mucosal Adjuvants and Cross-Reactivity with Variant Peptides of the Mucosal Immunity Induced by Injection of the Fusion Peptide PADRE-ELDKWA

ABSTRACT Secretory immunity protects against mucosal transmission of viruses, as demonstrated with the oral poliovirus vaccine. In a previous study we showed that this immunity could be induced in mice by injection of a fusion peptide consisting of an unnatural peptide-like sequence (PADRE) and a viral epitope (ELDKWASLW). PADRE is a T-helper-cell epitope able to bind most major histocompatibility complex class II molecules of different haplotypes in mice and humans and to increase antibody responses. ELDKWA is a well-known consensual sequence of gp41 involved in a key structure of human immunodeficiency virus (HIV) type 1. Here, the antibody response to the native form of ELDKWA was mainly of the immunoglobulin A isotype and selectively occurred in mucosa. Adjuvants, such as cholera toxin and cytosine polyguanine, were useless and even competed with PADRE for the response. Interestingly, these antibodies were cross-reactive with the three major variants of the epitope, as shown both by direct enzyme-linked immunosorbent assay and by inhibition. This unconventional route of mucosal immunization allows control of the administered dose. The lack of adjuvant and the cross-reactivity of the antibodies increase the safety and the spectrum of the candidate vaccine, respectively. The drug-like nature of the construct suggests further improvements by synthesis of more antigenic sequences. The reasonable cost of short peptides at the industrial level and their purity make this approach of interest for future vaccines against mucosal transmission of HIV or other pathogens.