Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular changes associated with the development of resistance to imatinib in an imatinib‐sensitive canine neoplastic mast cell line carrying a KIT c.1523A>T mutation

Although imatinib has therapeutic activity for certain subsets of patients with mastocytosis, it is not always curative. Here, molecular mechanisms that confer imatinib resistance to neoplastic mast cells were investigated using an imatinib‐sensitive canine neoplastic mast cell line VI‐MC carrying a KIT c.1523A>T activating mutation. Two imatinib‐resistant sublines were established by culturing VI‐MC cells in increasing concentrations of imatinib (1 μM resistant, rVI‐MC1; 10 μM resistant, rVI‐MC10). Both sublines had a second KIT mutation c.2443G>C. Recombinant KIT with the second mutation was insensitive to 1 μM but sensitive to 10 μM imatinib. The effect of imatinib on the phosphorylation of KIT and its downstream signalling proteins was then examined using these sublines. KIT and ERK were constitutively phosphorylated in both sublines, and their phosphorylation was suppressed by 10 μM imatinib in rVI‐MC1 cells. However, KIT but not ERK phosphorylation was suppressed in rVI‐MC10 cells. The phosphorylation of ERK in rVI‐MC10 cells was also not diminished by the Src family kinase (SFK) inhibitor dasatinib. This second mutation in KIT may play an important role in imatinib resistance in neoplastic mast cells. Furthermore, KIT/SFK‐independent activation of ERK would be involved in imatinib resistance when the neoplastic cells are exposed to higher concentrations of imatinib.
Toxoplasma gondii Serostatus Is Not Associated With Impaired Long-Term Survival after Heart Transplantation

Background Conflicting data have been reported about the effect of Toxoplasma serostatus on mortality after heart transplantation. Either a positive or a negative recipient Toxoplasma serostatus was found to be associated with increased mortality. Methods We evaluated the effects of T. gondii infection on survival of our 582 cardiac allograft recipients operated upon between June 1984 and July 2011. Results The 258 Toxoplasma seronegative and 324 seropositive recipients differed in age, pretransplantation diagnosis, ischemia time, renal function, donor Toxoplasma serology, and maintenance immunosuppression. After a median follow-up time of 8.3 years (range, 0–26 years), 117 (45%) seronegative and 219 (67%) seropositive patients died. No difference was found in deaths due to cardiac allograft vasculopathy. After adjustment for all relevant clinical characteristics, the recipient Toxoplasma serostatus was not associated with mortality (hazard ratio, 1.21; 95% confidence interval [CI], 0.95–1.54). With the Toxoplasma serostatus combination donor negative/recipient negative as a reference, univariate hazard ratios for the Toxoplasma serostatus combinations were D+/R- 0.52 (95% CI, 0.37–0.73), D-/R+ 0.65 (95% CI, 0.40–1.05), and D+/R+ 0.78 (95% CI, 0.57–1.07). Multivariate analysis, however, showed that donor Toxoplasma serostatus was not independently associated with mortality. Conclusions The Toxoplasma serostatus of both the recipient and donor appeared not to be independent risk factors for mortality after heart transplantation.
Phage Display against Corneal Epithelial Cells Produced Bioactive Peptides That Inhibit Aspergillus Adhesion to the Corneas

Dissection of host-pathogen interactions is important for both understanding the pathogenesis of infectious diseases and developing therapeutics for the infectious diseases like various infectious keratitis. To enhance the knowledge about pathogenesis infectious keratitis, a random 12-mer peptide phage display library was screened against cultured human corneal epithelial cells (HCEC). Fourteen sequences were obtained and BLASTp analysis showed that most of their homologue counterparts in GenBank were for defined or putative proteins in various pathogens. Based on known or predicted functions of the homologue proteins, ten synthetic peptides (Pc-A to Pc-J) were measured for their affinity to bind cells and their potential efficacy to interfere with pathogen adhesion to the cells. Besides binding to HCEC, most of them also bound to human corneal stromal cells and umbilical endothelial cells to different extents. When added to HCEC culture, the peptides induced expression of MyD88 and IL-17 in HCEC, and the stimulated cell culture medium showed fungicidal potency to various extents. While peptides Pc-C and Pc-E inhibited Aspergillus fumigatus (A.f) adhesion to HCEC in a dose-dependent manner, the similar inhibition ability of peptides Pc-A and Pc-B required presence of their homologue ligand Alb1p on A.f. When utilized in an eyeball organ culture model and an in vivo A.f keratitis model established in mouse, Pc-C and Pc-E inhibited fungal adhesion to corneas, hence decreased corneal disruption caused by inflammatory infiltration. Affinity pull-down of HCEC membrane proteins with peptide Pc-C revealed several molecules as potential receptors for this peptide. In conclusion, besides proving that phage display-selected peptides could be utilized to interfere with adhesion of pathogens to host cells, hence could be exploited for managing infectious diseases including infectious keratitis, we also proposed that the phage display technique and the resultant peptides could be used to explore host-pathogen interactions at molecular levels.
Enhancement of anti-leukemia activity of NK cells in vitro and in vivo by inhibition of leukemia cell-induced NK cell damage

Acute myeloid leukemia (AML) cells induce, in vitro, NK cell abnormalities (NKCAs) including apoptosis and activating receptor down-regulation. The potential negative impact of AML cells on the therapeutic efficacy of NK cell-based strategies prompted us to analyze the mechanisms underlying NKCAs and to develop approaches to protect NK cells from NKCAs. NKCA induction by the AML leukemia cells target a subpopulation of peripheral blood NK cells and is interleukin-2 independent but is abrogated by a long-term culture of NK (LTNK) cells at 37°C. LTNK cells displayed a significantly enhanced ability to damage AML cells in vitro and inhibited the subcutaneous growth of ML-2 cells grafted into CB17 SCID mice. Actinomycin D restored the susceptibility of LTNK cells to NKCAs while TAPI-0, a functional analog of the tissue inhibitor of metalloproteinase (TIMP) 3, inhibits ML-2 cell-induced NKCAs suggesting that the generation of NK cell resistance to NKCAs involves RNA transcription and metalloproteinase (MPP) inactivation. This conclusion is supported by the reduced susceptibility to AML cell-induced NKCAs of LTNK cells in which TIMP3 gene and protein are over-expressed. This information may contribute to the rational design of targeted strategies to enhance the efficacy of NK cell-based-immunotherapy of AML with haploidentical NK cells.
Mining Biological Data Using Self-Organizing Map

This paper presents a novel method of mining biological data using a self-organizing map (SOM). After partitioning a set of protein sequences using SOM, conventional homology alignment is applied to each cluster to determine the conserved local motif (biological pattern) for the cluster. These local motifs are then regarded as rules for prediction and classification. In the application to the prediction of HIV protease cleavage sites in proteins, we found that the rules derived from this method are much more robust than those derived from the decision tree method.
Positive genetic correlation between brain size and sexual traits in male guppies artificially selected for brain size

Brain size is an energetically costly trait to develop and maintain. Investments into other costly aspects of an organism's biology may therefore place important constraints on brain size evolution. Sexual traits are often costly and could therefore be traded off against neural investment. However, brain size may itself be under sexual selection through mate choice on cognitive ability. Here, we use guppy (Poecilia reticulata) lines selected for large and small brain size relative to body size to investigate the relationship between brain size, a large suite of male primary and secondary sexual traits, and body condition index. We found no evidence for trade‐offs between brain size and sexual traits. Instead, larger‐brained males had higher expression of several primary and precopulatory sexual traits – they had longer genitalia, were more colourful and developed longer tails than smaller‐brained males. Larger‐brained males were also in better body condition when housed in single‐sex groups. There was no difference in post‐copulatory sexual traits between males from the large‐ and small‐brained lines. Our data do not support the hypothesis that investment into sexual traits is an important limiting factor to brain size evolution, but instead suggest that brain size and several sexual traits are positively genetically correlated.
Comparative (Computational) Analysis of the DNA Methylation Status of Trinucleotide Repeat Expansion Diseases

Previous studies have examined DNA methylation in different trinucleotide repeat diseases. We have combined this data and used a pattern searching algorithm to identify motifs in the DNA surrounding aberrantly methylated CpGs found in the DNA of patients with one of the three trinucleotide repeat (TNR) expansion diseases: fragile X syndrome (FRAXA), myotonic dystrophy type I (DM1), or Friedreich's ataxia (FRDA). We examined sequences surrounding both the variably methylated (VM) CpGs, which are hypermethylated in patients compared with unaffected controls, and the nonvariably methylated CpGs which remain either always methylated (AM) or never methylated (NM) in both patients and controls. Using the J48 algorithm of WEKA analysis, we identified that two patterns are all that is necessary to classify our three regions CCGG∗ which is found in VM and not in AM regions and AATT∗ which distinguished between NM and VM + AM using proportional frequency. Furthermore, comparing our software with MEME software, we have demonstrated that our software identifies more patterns than MEME in these short DNA sequences. Thus, we present evidence that the DNA sequence surrounding CpG can influence its susceptibility to be de novo methylated in a disease state associated with a trinucleotide repeat.
Optimal Training for the SM-MIMO-OFDM Systems with MMSE Channel Estimation

Spatially multiplexed multiple-input-multiple-output orthogonal frequency division multiplexing (SM-MIMO-OFDM) systems are expected to provide a considerable increase of transmission capacity paving the way for the next generation broadband wireless communication standards. Considered MIMO-OFDM receiver performs estimation of the channel state information based on transmission of pilots concurrently with data symbols. The channel estimates are subsequently used for data detection. In this paper we discuss optimal placement and number of pilot subcarriers and derive the closed-form expression for the optimal power allocation between pilot and data symbols. The latter factor is important as under total transmit energy constraint there is a trade-off between boosting power of the pilot symbols to gain more accurate channel estimates and maintaining higher signal-to-noise ratio at the data subcarriers to minimise probability of detection error in the assumption of sufficiently reliable channel state information.
Tracing Functional Antigen-Specific CCR6+ Th17 Cells after Vaccination

Background The function of T helper cell subsets in vivo depends on their location, and one hallmark of T cell differentiation is the sequential regulation of migration-inducing chemokine receptor expression. CC-chemokine receptor 6 (CCR6) is a trait of tissue-homing effector T cells and has recently been described as a receptor on T helper type 17 (Th17) cells. Th17 cells are associated with autoimmunity and the defence against certain infections. Although, the polarization of Th cells into Th17 cells has been studied extensively in vitro, the development of those cells during the physiological immune response is still elusive. Methodology/Principal Findings We analysed the development and functionality of Th17 cells in immune-competent mice during an ongoing immune response. In naïve and vaccinated animals CCR6+ Th cells produce IL-17. The robust homeostatic proliferation and the presence of activation markers on CCR6+ Th cells indicate their activated status. Vaccination induces antigen-specific CCR6+ Th17 cells that respond to in vitro re-stimulation with cytokine production and proliferation. Furthermore, depletion of CCR6+ Th cells from donor leukocytes prevents recipients from severe disease in experimental autoimmune encephalomyelitis, a model for multiple sclerosis in mice. Conclusions/Significance In conclusion, we defined CCR6 as a specific marker for functional antigen-specific Th17 cells during the immune response. Since IL-17 production reaches the highest levels during the immediate early phase of the immune response and the activation of Th17 cells precedes the Th1 cell differentiation we tent to speculate that this particular Th cell subset may represent a first line effector Th cell subpopulation. Interference with the activation of this Th cell subtype provides an interesting strategy to prevent autoimmunity as well as to establish protective immunity against infections.
Limit order book transparency, execution risk, and market liquidity: Evidence from the Sydney Futures Exchange

This study provides new evidence regarding the effect of limit order book disclosure on trading behavior. The natural experiment affected by the Sydney Futures Exchange in January 2001, when it increased limit order book disclosure from depth at the best bid and ask prices to depth at the three best bid and ask prices is examined. Evidence was found consistent with a change in trading behavior coinciding with the increase in pre‐trade transparency. Consistent with predictions of a theoretical model based on execution risk, a statistically significant decline in depth was found at the best quotes. There is little evidence of an increase in bid‐ask spreads. Further, the proportion of market orders exceeding depth at the best quotes increases in a transparent limit order book, reflecting a reduction in execution risk. The study concludes that in a transparent market, limit order traders charge market order traders a higher premium for execution certainty by withdrawing depth from the best quotes, but not by increasing bid‐ask spreads. © 2006 Wiley Periodicals, Inc. Jrl Fut Mark 26:1147–1167, 2006
Semantic Segmentation Using Multiple Graphs with Block-Diagonal Constraints

In this paper we propose a novel method for image semantic segmentation using multiple graphs. The multiview affinity graph is constructed by leveraging the consistency between semantic space and multiple visualspaces. With block-diagonal constraints, we enforce the affinity matrix to be sparse such that the pairwise potential for dissimilar superpixels is close to zero. By a divide-and-conquer strategy, the optimizationfor learning affinity matrix is decomposed into several subproblems that can be solved in parallel. Using the neighborhood relationship between superpixels and the consistency between affinity matrix and labelconfidencematrix, we infer the semantic label for each superpixel of unlabeled images by minimizing an objective whose closed form solution can be easily obtained. Experimental results on two real-world image datasetsdemonstrate the effectiveness of our method.
Universality and Almost Decidability

We present and study new definitions of universal and programmable universal unary functions and consider a new simplicity criterion: almost decidability of the halting set. A set of positive integers S is almost decidable if there exists a decidable and generic i.e. a set of natural density one set whose intersection with S is decidable. Every decidable set is almost decidable, but the converse implication is false. We prove the existence of infinitely many universal functions whose halting sets are generic negligible, i.e. have density zero and not almost decidable. One result---namely, the existence of infinitely many universal functions whose halting sets are generic negligible and not almost decidable---solves an open problem in [9]. We conclude with some open problems.
Using a perception-based frequency scale in waveform interpolation

In speech coding it is important to focus the coding effort on the perceptually important features of the speech signal. This paper describes new quantization techniques which take advantage of current knowledge of human perception in speech coders. The new procedures exploit the frequency-dependent frequency resolution of the human auditory system. The methods are applied to the waveform interpolation (WI) coder, and their effectiveness is confirmed with experimental results. The principles described in the paper are not restricted to the WI coder, but are also applicable to many other speech coding algorithms.
Media audiences and the game of controversy

Abstract This article looks at the atmosphere of controversy or the perfume of scandal around reality TV. In order to grasp the feeling of controversy, we first look at the social and moral issues treated by reality programmes, where we try to introduce some positions in the overall reality TV debate. In a second step we argue that the controversial nature may reside in the intentional production or simulation of a (possible) moral panic, where we bring in recent reconfigurations about this critical sociological concept. One of the ideas here is that the old moral-panic model — what can be seen as a spiral effect produced by the interaction of the media, public opinion, interest groups, moral guardians and the authorities — needs to be adapted to a postmodern (media) environment. In this context we make a distinction between the moral- and media-panic concept. A third, more empirically based step in the attempt to understand the perfume of scandal deals with an audience study on how young people perceive new factual television and reality TV, including ‘extreme’ or more controversial forms of it.
Efficient Evaluation of Wind Turbine Noise

Wind turbines and residential areas are continuously coming closer due to expanding cities, rising demands on regenerative energy and limited suitable turbine locations. Wind turbines create noise during operation, such as every rotating system, which obviously influences or disturbs the environment and people living nearby. Standards like the IEC61400-11 regulate the maximum noise emission as well as measurement and analysis methods. These are rather complex as both changing environmental conditions and the operational state of the turbine have to be considered during the measurement. Further, a significant amount of data, especially the number of elements in each wind bin, has to be acquired. While common systems usually determine whether the turbine fulfills the requirements for operation or not, it is better being able to capture data flexibly according to the current environmental conditions, microphone positioning and switching of the current power curves. The measurement effort is reduced significantly. In order to be able to correlate measurement results to the wind turbine state, it is recommended to acquire not only standard relevant data but also additional data, such as rotational speed and vibration. Hence it is possible to detect error sources during the development process and find suitable solutions easier.
Investigating the path of plastid genome degradation in an early-transitional clade of heterotrophic orchids, and implications for heterotrophic angiosperms.

Parasitic organisms exemplify morphological and genomic reduction. Some heterotrophic, parasitic plants harbor drastically reduced and degraded plastid genomes resulting from relaxed selective pressure on photosynthetic function. However, few studies have addressed the initial stages of plastome degradation in groups containing both photosynthetic and nonphotosynthetic species. Corallorhiza is a genus of leafless, heterotrophic orchids that contains both green, photosynthetic species and nongreen, putatively nonphotosynthetic species, and represents an ideal system in which to assess the beginning of the transition to a "minimal plastome. " Complete plastomes were generated for nine taxa of Corallorhiza using Illumina paired-end sequencing of genomic DNA to assess the degree of degradation among taxa, and for comparison with a general model of degradation among angiosperms. Quantification of total chlorophyll suggests that nongreen Corallorhiza still produce chlorophyll, but at 10-fold lower concentrations than green congeners. Complete plastomes and partial nuclear rDNA cistrons yielded a fully resolved tree for Corallorhiza, with at least two independent losses of photosynthesis, evidenced by gene deletions and pseudogenes in Co. striata and nongreen Co. maculata. All Corallorhiza show some evidence of degradation in genes of the NAD(P)H dehydrogenase complex. Among genes with open reading frames, photosynthesis-related genes displayed evidence of neutral evolution in nongreen Corallorhiza, whereas genes of the ATP synthase complex displayed some evidence of positive selection in these same groups, though for reasons unknown. Corallorhiza spans the early stages of a general model of plastome degradation and has added critical insight for understanding the process of plastome evolution in heterotrophic angiosperms.
Young people’s everyday romance and sexual experiences in relation to sex-related conversations with parents: a diary study in the Netherlands

Abstract This study builds on existing research into how young people’s emergent sexual development is connected to parent–child sex-related communication through avoidance vs. disclosure. Over the course of one year, a total of 21 young people (age range 12–17.5) reported in longitudinal qualitative diaries their (1) everyday sexual experiences and (2) sex-related conversations with their parents. Using a mixed-methods approach, findings show that less sexually experienced participants reported greater avoidance of parent–child sex-related conversations than more experienced participants. The sex-related conversations of more experienced participants mainly concerned overt experiences in the form of everyday issues with their romantic partner, while the conversations of less experienced participants were characterised by more covert experiences such as opinions about romantic relationships in general. These results suggest that the degree to which young people feel comfortable talking about sexuality with their parents partly depends on when the conversation takes place during a young person’s romantic and sexual development.