Miracle-dz/UniFAR-FTUs huggingface dataset:
Oncogenic KIT-induced aggressive systemic mastocytosis requires SHP2/PTPN11 phosphatase for disease progression in mice

Acquired mutations in KIT are driver mutations in systemic mastocytosis (SM). Here, we tested the role of SHP2/PTPN11 phosphatase in oncogenic KIT signaling using an aggressive SM mouse model. Stable knock-down (KD) of SHP2 led to impaired growth, colony formation, and increased rates of apoptosis in P815 cells. This correlated with defects in signaling to ERK/Bim, Btk, Lyn, and Stat5 pathways in P815-KD cells compared to non-targeting (NT). Retro-orbital injections of P815 NT cells in syngeneic DBA/2 mice resulted in rapid development of aggressive SM within 13-16 days characterized by splenomegaly, extramedullary hematopoiesis, and multifocal liver tumors. In contrast, mice injected with P815 SHP2 KD cells showed less disease burden, including normal spleen weight and cellularity, and significant reductions in mastocytoma cells in spleen, bone marrow, peripheral blood and liver compared to NT controls. Treatment of human mast cell leukemia HMC-1 cells or P815 cells with SHP2 inhibitor II-B08, resulted in reduced colony formation and cell viability. Combining II-B08 with multi-kinase inhibitor Dasatinib showed enhanced efficacy than either inhibitor alone in blocking cell growth pathways and cell viability. Taken together, these results identify SHP2 as a key effector of oncogenic KIT and a therapeutic target in aggressive SM.
A Hierarchical Video Annotation System

Semantic search service is generally considered to include text search, audio search, and video search. The annotation of a video is crucial to the success of video search and retrieval. With the precise annotation of video files and their semantic reasoning, more accurate search results according to the users’ query intention can be obtained. In this paper, a prototype of such a video annotation system, called Semantic Video Annotation System (SVAS), is presented. SVAS uses a three-level annotation architecture and a semantic video search language called Semantic Query Description Language for Video (SQDL-V). SQDL-V engine based on SVAS is able to return more accurate search results in comparison to the formal video search method.
Environmental Symbiont Acquisition May Not Be the Solution to Warming Seas for Reef-Building Corals

Background Coral reefs worldwide are in decline. Much of the mortality can be attributed to coral bleaching (loss of the coral's intracellular photosynthetic algal symbiont) associated with global warming. How corals will respond to increasing oceanic temperatures has been an area of extensive study and debate. Recovery after a bleaching event is dependent on regaining symbionts, but the source of repopulating symbionts is poorly understood. Possibilities include recovery from the proliferation of endogenous symbionts or recovery by uptake of exogenous stress-tolerant symbionts. Methodology/Principal Findings To test one of these possibilities, the ability of corals to acquire exogenous symbionts, bleached colonies of Porites divaricata were exposed to symbiont types not normally found within this coral and symbiont acquisition was monitored. After three weeks exposure to exogenous symbionts, these novel symbionts were detected in some of the recovering corals, providing the first experimental evidence that scleractinian corals are capable of temporarily acquiring symbionts from the water column after bleaching. However, the acquisition was transient, indicating that the new symbioses were unstable. Only those symbiont types present before bleaching were stable upon recovery, demonstrating that recovery was from the resident in situ symbiont populations. Conclusions/Significance These findings suggest that some corals do not have the ability to adjust to climate warming by acquiring and maintaining exogenous, more stress-tolerant symbionts. This has serious ramifications for the success of coral reefs and surrounding ecosystems and suggests that unless actions are taken to reverse it, climate change will lead to decreases in biodiversity and a loss of coral reefs.
Emotionface: Prototype Facial Expression Display of Emotion in Music

EmotionFace is a software interface for visually displaying the self-reported emotion expressed by music. Taken in reverse, it can be viewed as a facial expression whose auditory connection or exemplar is the time synchronized, associated music. The present instantiation of the software uses a simple schematic face with eyes and mouth moving according to a parabolic model: Smiling and frowning of mouth represents valence (happiness and sadness) and amount of opening of eyes represents arousal. Continuous emotional responses to music collected in previous research have been used to test and calibrate EmotionFace. The interface provides an alternative to the presentation of data on a two-dimensional emotion-space, the same space used for the collection of emotional data in response to music. These synthesized facial expressions make the observation of the emotion data expressed by music easier for the human observer to process and may be a more natural interface between the human and computer. Future research will include optimization of EmotionFace, using more sophisticated algorithms and facial expression databases, and the examination of the lag structure between facial expression and musical structure. Eventually, with more elaborate systems, automation and greater knowledge of emotion and associated musical structure, it may be possible to compose music meaningfully from synthesized and real facial expressions.
Replacement of Dietary Saturated Fat by PUFA-Rich Pumpkin Seed Oil Attenuates Non-Alcoholic Fatty Liver Disease and Atherosclerosis Development, with Additional Health Effects of Virgin over Refined Oil

Background and Aims As dietary saturated fatty acids are associated with metabolic and cardiovascular disease, a potentially interesting strategy to reduce disease risk is modification of the quality of fat consumed. Vegetable oils represent an attractive target for intervention, as they largely determine the intake of dietary fats. Furthermore, besides potential health effects conferred by the type of fatty acids in a vegetable oil, other minor components (e.g. phytochemicals) may also have health benefits. Here, we investigated the potential long-term health effects of isocaloric substitution of dietary fat (i.e. partial replacement of saturated by unsaturated fats), as well as putative additional effects of phytochemicals present in unrefined (virgin) oil on development of non-alcoholic fatty liver disease (NAFLD) and associated atherosclerosis. For this, we used pumpkin seed oil, because it is high in unsaturated fatty acids and a rich source of phytochemicals. Methods ApoE*3Leiden mice were fed a Western-type diet (CON) containing cocoa butter (15% w/w) and cholesterol (1% w/w) for 20 weeks to induce risk factors and disease endpoints. In separate groups, cocoa butter was replaced by refined (REF) or virgin (VIR) pumpkin seed oil (comparable in fatty acid composition, but different in phytochemical content). Results Both oils improved dyslipidaemia, with decreased (V)LDL-cholesterol and triglyceride levels in comparison with CON, and additional cholesterol-lowering effects of VIR over REF. While REF did not affect plasma inflammatory markers, VIR reduced circulating serum amyloid A and soluble vascular adhesion molecule-1. NAFLD and atherosclerosis development was modestly reduced in REF, and VIR strongly decreased liver steatosis and inflammation as well as atherosclerotic lesion area and severity. Conclusions Overall, we show that an isocaloric switch from a diet rich in saturated fat to a diet rich in unsaturated fat can attenuate NAFLD and atherosclerosis development. Phytochemical-rich virgin pumpkin seed oil exerts additional anti-inflammatory effects resulting in more pronounced health effects.
TLR Signaling Tailors Innate Immune Responses in Human Microglia and Astrocytes1

The specific signals mediating the activation of microglia and astrocytes as a prelude to, or consequence of, CNS inflammation continue to be defined. We investigated TLRs as novel receptors mediating innate immune responses in human glial cells. We find that microglia express mRNA for TLRs 1–9, whereas astrocytes express robust TLR3, low-level TLR 1, 4, 5, and 9, and rare-to-undetectable TLR 2, 6, 7, 8, and 10 mRNA (quantitative real-time PCR). We focused on TLRs 3 and 4, which can signal through both the MyD88-dependent and -independent pathways, and on the MyD88-restricted TLR2. By flow cytometry, we established that microglia strongly express cell surface TLR2; TLR3 is expressed at higher levels intracellularly. Astrocytes express both cell surface and intracellular TLR3. All three TLRs trigger microglial activation upon ligation. TLR3 signaling induces the strongest proinflammatory polarizing response, characterized by secretion of high levels of IL-12, TNF-α, IL-6, CXCL-10, and IL-10, and the expression of IFN-β. CXCL-10 and IL-10 secretion following TLR4 ligation are comparable to that of TLR3; however, other responses were lower or absent. TLR2-mediated responses are dominated by IL-6 and IL-10 secretion. Astrocytes respond to TLR3 ligation, producing IL-6, CXCL-10, and IFN-β, implicating these cells as contributors to proinflammatory responses. Initial TLR-mediated glial activation also regulates consequent TLR expression; while TLR2 and TLR3 are subject to positive feedback, TLR4 is down-regulated in microglia. Astrocytes up-regulate all three TLRs following TLR3 ligation. Our data indicate that activation of innate immune responses in the CNS is not homogeneous but rather tailored according to cell type and environmental signal.
HIEDS: A Generic and Efficient Approach to Hierarchical Dataset Summarization

The rapid growth of open data on the Web promotes the development of data portals that facilitate finding useful datasets. To help users quickly inspect a dataset found in a portal, we propose to summarize its contents and generate a hierarchical grouping of entities connected by relations. Our generic approach, called HIEDS, considers coverage of dataset, height of hierarchy, cohesion within groups, overlap between groups, and homogeneity of groups, and integrates these configurable factors into a combinatorial optimization problem to solve. We present an efficient solution, to serve users with dynamically configured summaries with acceptable latency. We systematically experiment with our approach on real-world RDF datasets.
Affect and Wellbeing: Introduction to Special Section

The authors first give a brief overview of how computers can afford multiple forms of transformational experiences. Some of these experiences can be purposely designed, for example, to detect and regulate students' affective states to improve aspects of their learning experiences. They can also be used in computer-based psychological interventions that treat psychological illness or that preventively promote wellbeing, healthy lifestyles, and mental health. This special section aims to contribute ideas, methods and case studies for how affective computing can move toward the goal of promoting wellbeing. The papers spread across some of the multiple modalities and techniques used to perceive and detect affect from text, physiology facial expressions, and gaze, and some of the approaches to analyze the expression of sentiments shared via online communities by depressed patients. The articles in this special section discuss how information that computers collect about our behaviour, cognition - and particularly affect - can be used in the further understanding, nurturing or development of wellbeing and human strengths: e.g. self-understanding, empathy, intrinsic motivation toward wellbeing healthy lifestyles.
Confirming the QSR Promise

Within the qualitative spatial reasoning community it has been a widely accepted commonplace that reasoning in qualitative constraint calculi outperforms reasoning in other more general and expressive formalisms. To check the correctness of this assumption we conducted some empirical case studies in which we compared the performance of a qualitative constraint solver with different automated reasoning systems, namely first-order and description logic reasoners. We also report on some first results from comparing the performance of qualitative and finite constraint solvers. Our empirical tests are based on randomly generated instances of qualitative constraint satisfaction problems, which have been encoded as reasoning problems for first-order reasoners, description logic reasoners, and finite CSP solvers, respectively. Given our currently used encodings, these studies show that first-order and description logic reasoners are far from being feasible for problem sizes that can easily be solved by a qualitative reasoner. In contrast, finite CSP solvers are competitive, but still outperformed by a qualitative reasoner on the problem instances considered here.
Enjoyment of music by elderly hearing-impaired listeners.

BACKGROUND Anecdotal evidence suggests that hearing loss interferes with the enjoyment of music, although it is not known how widespread this problem currently is. PURPOSE To estimate the prevalence of music-listening difficulties among a group of elderly hearing aid wearers. RESEARCH DESIGN Interview. Telephone interviews were conducted with patients who wore hearing aids. Questions regarding several aspects of music listening were included. STUDY SAMPLE Sixty-eight hearing-impaired people served as subjects. They had all been seen in the audiology clinic for hearing aid evaluation during the previous year. DATA COLLECTION AND ANALYSIS Subjects were asked questions concerning their use of hearing aids, the importance of listening to music in their lives, their habits and practices concerning music, and difficulties they experienced in listening to music. RESULTS Almost 30% of the respondents reported that their hearing losses affected their enjoyment of music. About half of the respondents indicated that music was either too loud or too soft, although only about one-third reported difficulties with level contrasts within musical pieces. In contrast to a similar survey carried out 20 years ago, there were many fewer complaints about listening to music. This result may be due in large part to improvements in hearing aids, especially with regard to nonlinear compression. CONCLUSIONS Although new hearing aid technologies have somewhat reduced problems of music enjoyment experienced by hearing-impaired people, audiologists should be aware that some 25-30% of patients may have difficulties with listening to music and may require extra attention to minimize those problems.
Paradoxical role of antibodies in dengue virus infections: considerations for prophylactic vaccine development

ABSTRACT Highly effective prophylactic vaccines for flaviviruses including yellow fever virus, tick-borne encephalitis virus and Japanese encephalitis virus are currently in use. However, the development of a dengue virus (DENV) vaccine has been hampered by the requirement of simultaneous protection against four distinct serotypes and the threat that DENV-specific antibodies might either mediate neutralization or, on the contrary, exacerbate disease through the phenomenon of antibody-dependent enhancement (ADE) of infection. Therefore, understanding the cellular, biochemical and molecular basis of antibody-mediated neutralization and ADE are fundamental for the development of a safe DENV vaccine. Here we summarize current structural and mechanistic knowledge underlying these phenomena. We also review recent results demonstrating that the humoral immune response triggered during natural DENV infection is able to generate neutralizing antibodies binding complex quaternary epitopes only present on the surface of intact virions.
Empirical evidence about the UML: a systematic literature review

The Unified Modeling Language (UML) was created on the basis of expert opinion and has now become accepted as the ‘standard’ object‐oriented modelling notation. Our objectives were to determine how widely the notations of the UML, and their usefulness, have been studied empirically, and to identify which aspects of it have been studied in most detail. We undertook a mapping study of the literature to identify relevant empirical studies and to classify them in terms of the aspects of the UML that they studied. We then conducted a systematic literature review, covering empirical studies published up to the end of 2008, based on the main categories identified. We identified 49 relevant publications, and report the aggregated results for those categories for which we had enough papers— metrics, comprehension, model quality, methods and tools and adoption. Despite indications that a number of problems exist with UML models, researchers tend to use the UML as a ‘given’ and seem reluctant to ask questions that might help to make it more effective. Copyright © 2010 John Wiley & Sons, Ltd.
Diagnosis and Management of Trichomoniasis in Men and Women*

Trichomonas vaginalis iscommonly foundinthe genito-urinary tracts ofmenandwomen.Studies of different groups ofwomenhaveshownanincidence varying fromnilinvirgins (Jirovec, Breindl, Kucera, andSebek, 1942) tohighlevels insexually active womenpresenting withvaginal discharge. Buxton, Weinman, andJohnson (1958) found noevidence of trichomoniasis in157female undergraduates of whomonly10weremarried, buttheyfoundthat70 percent. of221female prisoners wereinfested; 6-3 percent. ofmarried female employees ofaninsurancecompanywerefoundtobeinfested compared with1*4percent. ofunmarried female employees. IntheWhitechapel Clinic during theyearbeginningJuly1,1960,routine tests fortrichomonal infestation werepositive in449(315percent.) of 1,424 womenandin92(56percent.) of1,646 men with non-gonococcal urethritis (Wisdom andDunlop, 1965). Search forT.vaginalis istherefore ofimportanceintheinvestigation ofpatients exposed to sexually transmitted disease. Thediagnosis ismade byfinding T.vaginalis inwetsmearorinculture.
Compiler-driven dynamic reliability management for on-chip systems under variabilities

This paper presents a novel Dynamic Reliability Management System (DyReMS) for on-chip systems that performs resilience-driven resource allocation and mapping. It accounts for both the tasks' resilience properties and heterogeneous error recovery features of different cores. DyReMS also chooses a reliable task version (out of multiple reliability-aware transformed options) depending upon the reliability level of the allocated core. In case of error detection, rollbacks are performed. Our system provides 70%-87% improved task reliability compared to a timing reliability-optimizing core assignment, i.e. minimizing the probability of deadline misses (with EDF scheduling).
Circadian rhythms in reward and underlying neural circuits

Studies suggest that the circadian timing system exerts an important influence on responses to rewarding stimuli. Diurnal rhythms in the rewarding value of amphetamine and mating behavior were observed, but differed in the pattern of their timing. Daily fluctuations in reward were correlated with oscillations in mesolimbic dopaminergic activity in both the nucleus accumbens (NAc) and ventral tegmental area (VTA), with a peak in NAc coinciding with the peak of sex reward, while the peak in the VTA associated with the peak in amphetamine reward. Also, rhythmic expression of the marker of neural activation, cFos, was observed in NAc, medial prefrontal cortex (mPFC), and VTA, with peak expression during the late night. Rhythmic clock protein expression was observed in the NAc, suggesting intrinsic circadian regulation of reward. However, absence of clock gene oscillations in the VTA suggests that rhythms in mesolimbic activity are also driven by a timing signal originating elsewhere; and the mPFC was hypothesized to be a key mediator. The effects of mPFC lesions or inactivation on diurnal rhythms in neural activation and amphetamine reward were determined. Lesions attenuated the peak in cFos-IR in the NAc, eliminating the diurnal rhythm, but had no effect on VTA rhythms. Moreover, daily differences in amphetamine reward were eliminated by mPFC lesions and inactivation, via an increase at the nadir. Together, these results indicate that diurnal rhythms of mesolimbic activity may be functionally relevant for rhythms in reward and that the mPFC plays a critical role in mediating such diurnal fluctuations.
A Characterisation of First-Order Constraint Satisfaction Problems

We characterise finite relational core structures admitting finitely many obstructions, in terms of special near unanimity functions, and in terms of dismantling properties of their square. As a consequence, we show that it is decidable to determine whether a constraint satisfaction problem is first-order definable: we show the general problem to be NP-complete, and give a polynomial-time algorithm in the case of cores
Anti-pig IgM antibodies in human serum react predominantly with Gal(alpha 1-3)Gal epitopes.

A major problem with pig-to-human-tissue xenograft studies is that humans have natural antibodies to pig cells; these antibodies would cause hyperacute rejection if pig tissues were xenografted to humans. Here we show that most of human IgM antibodies present in the serum of healthy donors and reactive with pig cells react with galactose in an (alpha 1-3) linkage with galactose--i.e., Gal(alpha 1-3)Gal. Absorption studies demonstrated that the antibodies detected the same or similar epitopes on the surface of pig erythrocytes, blood and splenic lymphocytes, and aortic endothelial cells (EC). The antibodies were sensitive to 2-mercaptoethanol (2ME) treatment, did not bind to protein A or G, and were present in the high molecular weight fraction of serum; they are clearly IgM antibodies. Further, the antibodies did not react with human ABO blood group substances and are not related to human blood group A or B, which carry a terminal galactose. The reaction of human serum with pig erythrocytes was specifically inhibited by mono- and disaccharides: D-galactose, melibiose, stachyose, methyl-alpha-D-galactopyranoside, and D-galactosamine but not by D-glucose or methyl-beta-D-galactopyranoside; demonstrating that the reaction is with galactose in an alpha and not a beta linkage. A cDNA clone encoding the murine alpha-1,3-galactosyltransferase (which transfers a terminal galactose residue with an (alpha 1-3) linkage to a subterminal galactose) was isolated by polymerase chain reaction (PCR), cloned, and transfected into COS cells, which are of Old World monkey origin and, like humans, do not express Gal(alpha 1-3)Gal. After transfection, COS cells became strongly reactive with human serum and with IB4 lectin [which reacts only with Gal(alpha 1-3)Gal]; this reactivity could be removed by absorption with pig erythrocytes. As most of the antibody reacting with pig cells can be removed by absorption with either melibiose or Gal(alpha 1-3)Gal+ COS cells, most of these react with Gal(alpha 1-3)Gal. These findings provide the basis for genetic manipulation of the pig alpha-1,3-galactosyltransferase for future transplantation studies.