Miracle-dz/UniFAR-FTUs huggingface dataset:
Inverse Visual Question Answering: A New Benchmark and VQA Diagnosis Tool

In recent years, visual question answering (VQA) has become topical. The premise of VQA's significance as a benchmark in AI, is that both the image and textual question need to be well understood and mutually grounded in order to infer the correct answer. However, current VQA models perhaps ‘understand’ less than initially hoped, and instead master the easier task of exploiting cues given away in the question and biases in the answer distribution [1] . In this paper we propose the inverse problem of VQA (iVQA). The iVQA task is to generate a question that corresponds to a given image and answer pair. We propose a variational iVQA model that can generate diverse, grammatically correct and content correlated questions that match the given answer. Based on this model, we show that iVQA is an interesting benchmark for visuo-linguistic understanding, and a more challenging alternative to VQA because an iVQA model needs to understand the image better to be successful. As a second contribution, we show how to use iVQA in a novel reinforcement learning framework to diagnose any existing VQA model by way of exposing its belief set: the set of question-answer pairs that the VQA model would predict true for a given image. This provides a completely new window into what VQA models ‘believe’ about images. We show that existing VQA models have more erroneous beliefs than previously thought, revealing their intrinsic weaknesses. Suggestions are then made on how to address these weaknesses going forward.
A DNA ‘Barcode Blitz’: Rapid Digitization and Sequencing of a Natural History Collection

DNA barcoding protocols require the linkage of each sequence record to a voucher specimen that has, whenever possible, been authoritatively identified. Natural history collections would seem an ideal resource for barcode library construction, but they have never seen large-scale analysis because of concerns linked to DNA degradation. The present study examines the strength of this barrier, carrying out a comprehensive analysis of moth and butterfly (Lepidoptera) species in the Australian National Insect Collection. Protocols were developed that enabled tissue samples, specimen data, and images to be assembled rapidly. Using these methods, a five-person team processed 41,650 specimens representing 12,699 species in 14 weeks. Subsequent molecular analysis took about six months, reflecting the need for multiple rounds of PCR as sequence recovery was impacted by age, body size, and collection protocols. Despite these variables and the fact that specimens averaged 30.4 years old, barcode records were obtained from 86% of the species. In fact, one or more barcode compliant sequences (>487 bp) were recovered from virtually all species represented by five or more individuals, even when the youngest was 50 years old. By assembling specimen images, distributional data, and DNA barcode sequences on a web-accessible informatics platform, this study has greatly advanced accessibility to information on thousands of species. Moreover, much of the specimen data became publically accessible within days of its acquisition, while most sequence results saw release within three months. As such, this study reveals the speed with which DNA barcode workflows can mobilize biodiversity data, often providing the first web-accessible information for a species. These results further suggest that existing collections can enable the rapid development of a comprehensive DNA barcode library for the most diverse compartment of terrestrial biodiversity – insects.
Collaboration and co-location: Making sense of digital design for early childhood games

The relationship between physical activity and educational and health outcomes is well known. As the significance of digital devices continues to increase, along with societal reliance on them, the provision of programs that draw technology and physical activity together is increasingly important. The recent Pokemon phenomenon is an example of a digitally-driven physical activity that appealed to both adults and children alike. This paper reports on the proof of concept phase of a development that brings to digital life a physical activity program designed specifically for preschoolers. The aim of the JumpStart project was to find a way to engage more parents with their children in a physical activity. The brief from the customer was to ensure that the app was appealing to both parent and child with the view to creating a double motivation (push from the child and the parent). It was found through the design process that it was important for the application to appeal to both the child and their significant adult who would be an active participant in explaining and teaching the various skills. The proof of concept phase was introduced to a small group of child users. Informal feedback was collected to inform the completion of the proof of concept. Through the feedback, refinement of the design characteristics was uncovered which allowed a more comprehensive specification to be developed. Based on this proof of concept, the full application is now in development, continuing to explore the connection between co-location and collaboration in digital game design for preschoolers in a more comprehensive research study.
Genetics and Molecular Biology of Epstein-Barr Virus-Encoded BART MicroRNA: A Paradigm for Viral Modulation of Host Immune Response Genes and Genome Stability

Epstein-Barr virus, a ubiquitous human herpesvirus, is associated through epidemiologic evidence with common autoimmune syndromes and cancers. However, specific genetic mechanisms of pathogenesis have been difficult to identify. In this review, the author summarizes evidence that recently discovered noncoding RNAs termed microRNA encoded by Epstein-Barr virus BARF (BamHI A right frame) termed BART (BamHI A right transcripts) are modulators of human immune response genes and genome stability in infected and bystander cells. BART expression is apparently regulated by complex feedback loops with the host immune response regulatory NF-κB transcription factors. EBV-encoded BZLF-1 (ZEBRA) protein could also regulate BART since ZEBRA contains a terminal region similar to ankyrin proteins such as IκBα that regulate host NF-κB. BALF-2 (BamHI A left frame transcript), a viral homologue of the immunoglobulin and T cell receptor gene recombinase RAG-1 (recombination-activating gene-1), may also be coregulated with BART since BALF-2 regulatory sequences are located near the BART locus. Viral-encoded microRNA and viral mRNA transferred to bystander cells through vesicles, defective viral particles, or other mechanisms suggest a new paradigm in which bystander or hit-and-run mechanisms enable the virus to transiently or chronically alter human immune response genes as well as the stability of the human genome.
A targeted RNAi screen identifies factors affecting diverse stages of receptor-mediated transcytosis

Endosome transport by transcytosis is the primary mechanism by which proteins and other large cargo traverse epithelial barriers in normal tissue. Transcytosis is also essential for establishing and maintaining membrane polarity in epithelia and other polarized cells. To identify novel components of this pathway, we conducted a high-throughput RNA interference screen for factors necessary for the bidirectional transcytosis of IgG by the Fc&ggr; receptor FcRn. This screen identified 23 genes whose suppression resulted in a reproducible decrease in FcRn-mediated transcytosis. Pulse-chase kinetic transport assays on four of the top-ranking genes (EXOC2, EXOC7, PARD6B, and LEPROT) revealed distinct effects on the apical and basolateral recycling and transcytotic pathways, demonstrating that these pathways are genetically separable. We also found a strong dependence on PARD6B for apical, but not basolateral, recycling, implicating this cell polarity gene in assembly or maintenance of the apical endosomal system. This dataset yields insights into how vesicular transport is adapted to the specialized functions of differentiated cell types and opens new research avenues into epithelial trafficking.
Molecular Mechanisms of Human Disease Mediated by Oncogenic and Primary Immunodeficiency Mutations in Class IA Phosphoinositide 3-Kinases

The signaling lipid phosphatidylinositol 3,4,5, trisphosphate (PIP3) is an essential mediator of many vital cellular processes, including growth, survival, and metabolism. PIP3 is generated through the action of the class I phosphoinositide 3-kinases (PI3K), and their activity is tightly controlled through interactions with regulatory proteins and activating stimuli. The class IA PI3Ks are composed of three distinct p110 catalytic subunits (p110α, p110β, and p110δ), and they play different roles in specific tissues due to disparities in both expression and engagement downstream of cell-surface receptors. Disruption of PI3K regulation is a frequent driver of numerous human diseases. Activating mutations in the PIK3CA gene encoding the p110α catalytic subunit of class IA PI3K are frequently mutated in several cancer types, and mutations in the PIK3CD gene encoding the p110δ catalytic subunit have been identified in primary immunodeficiency patients. All class IA p110 subunits interact with p85 regulatory subunits, and mutations/deletions in different p85 regulatory subunits have been identified in both cancer and primary immunodeficiencies. In this review, we will summarize our current understanding for the molecular basis of how class IA PI3K catalytic activity is regulated by p85 regulatory subunits, and how activating mutations in the PI3K catalytic subunits PIK3CA and PIK3CD (p110α, p110δ) and regulatory subunits PIK3R1 (p85α) mediate PI3K activation and human disease.
Bevacizumab for Metastatic Colorectal Cancer: A Global Cost-Effectiveness Analysis.

BACKGROUND In the U.S., the addition of bevacizumab to first-line chemotherapy in metastatic colorectal cancer (mCRC) has been demonstrated to provide 0.10 quality-adjusted life years (QALYs) at an incremental cost-effectiveness ratio (ICER) of $571,000/QALY. Due to variability in pricing, value for money may be different in other countries. Our objective was to establish the cost-effectiveness of bevacizumab in mCRC in the U.S., U.K., Canada, Australia, and Israel. METHODS We performed the analysis using a previously established Markov model for mCRC. Input data for efficacy, adverse events, and quality of life were considered to be generalizable and therefore identical for all countries. We used country-specific prices for medications, administration, and other health service costs. All costs were converted from local currency to U.S. dollars at the exchange rates in March 2016. We conducted one-way and probabilistic sensitivity analyses (PSA) to assess the model robustness across parameter uncertainties. RESULTS Base case results demonstrated that the highest ICER was in the U.S. ($571,000/QALY) and the lowest was in Australia ($277,000/QALY). In Canada, the U.K., and Israel, ICERs ranged between $351,000 and $358,000 per QALY. PSA demonstrated 0% likelihood of bevacizumab being cost-effective in any country at a willingness to pay threshold of $150,000 per QALY. CONCLUSION The addition of bevacizumab to first-line chemotherapy for mCRC consistently fails to be cost-effective in all five countries. There are large differences in cost-effectiveness between countries. This study provides a framework for analyzing the value of a cancer drug from the perspectives of multiple international payers. IMPLICATIONS FOR PRACTICE The cost-effectiveness of bevacizumab varies significantly between multiple countries. By conventional thresholds, bevacizumab is not cost-effective in metastatic colon cancer in the U.S., the U.K., Australia, Canada, and Israel.
Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids

ABSTRACT Recent estimates suggest that >300 million people are afflicted by serious fungal infections worldwide. Current antifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of new antifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi. In this study, we screened a synthetic drug library for compounds that target the synthesis of fungal, but not mammalian, GlcCer and found two compounds [N′-(3-bromo-4-hydroxybenzylidene)-2-methylbenzohydrazide (BHBM) and its derivative, 3-bromo-N′-(3-bromo-4-hydroxybenzylidene) benzohydrazide (D0)] that were highly effective in vitro and in vivo against several pathogenic fungi. BHBM and D0 were well tolerated in animals and are highly synergistic or additive to current antifungals. BHBM and D0 significantly affected fungal cell morphology and resulted in the accumulation of intracellular vesicles. Deep-sequencing analysis of drug-resistant mutants revealed that four protein products, encoded by genes APL5, COS111, MKK1, and STE2, which are involved in vesicular transport and cell cycle progression, are targeted by BHBM. IMPORTANCE Fungal infections are a significant cause of morbidity and mortality worldwide. Current antifungal drugs suffer from various drawbacks, including toxicity, drug resistance, and narrow spectrum of activity. In this study, we have demonstrated that pharmaceutical inhibition of fungal glucosylceramide presents a new opportunity to treat cryptococcosis and various other fungal infections. In addition to being effective against pathogenic fungi, the compounds discovered in this study were well tolerated by animals and additive to current antifungals. These findings suggest that these drugs might pave the way for the development of a new class of antifungals. Fungal infections are a significant cause of morbidity and mortality worldwide. Current antifungal drugs suffer from various drawbacks, including toxicity, drug resistance, and narrow spectrum of activity. In this study, we have demonstrated that pharmaceutical inhibition of fungal glucosylceramide presents a new opportunity to treat cryptococcosis and various other fungal infections. In addition to being effective against pathogenic fungi, the compounds discovered in this study were well tolerated by animals and additive to current antifungals. These findings suggest that these drugs might pave the way for the development of a new class of antifungals.
How Effective Are DNA Barcodes in the Identification of African Rainforest Trees?

Background DNA barcoding of rain forest trees could potentially help biologists identify species and discover new ones. However, DNA barcodes cannot always distinguish between closely related species, and the size and completeness of barcode databases are key parameters for their successful application. We test the ability of rbcL, matK and trnH-psbA plastid DNA markers to identify rain forest trees at two sites in Atlantic central Africa under the assumption that a database is exhaustive in terms of species content, but not necessarily in terms of haplotype diversity within species. Methodology/Principal Findings We assess the accuracy of identification to species or genus using a genetic distance matrix between samples either based on a global multiple sequence alignment (GD) or on a basic local alignment search tool (BLAST). Where a local database is available (within a 50 ha plot), barcoding was generally reliable for genus identification (95–100% success), but less for species identification (71–88%). Using a single marker, best results for species identification were obtained with trnH-psbA. There was a significant decrease of barcoding success in species-rich clades. When the local database was used to identify the genus of trees from another region and did include all genera from the query individuals but not all species, genus identification success decreased to 84–90%. The GD method performed best but a global multiple sequence alignment is not applicable on trnH-psbA. Conclusions/Significance Barcoding is a useful tool to assign unidentified African rain forest trees to a genus, but identification to a species is less reliable, especially in species-rich clades, even using an exhaustive local database. Combining two markers improves the accuracy of species identification but it would only marginally improve genus identification. Finally, we highlight some limitations of the BLAST algorithm as currently implemented and suggest possible improvements for barcoding applications.
Janus and PI3-kinases mediate glucocorticoid resistance in activated chronic leukemia cells

Glucorticoids (GCs) such as dexamethasone (DEX) remain important treatments for Chronic Lymphocytic Leukemia (CLL) but the mechanisms are poorly understood and resistance is inevitable. Proliferation centers (PC) in lymph nodes and bone marrow offer protection against many cytotoxic drugs and circulating CLL cells were found to acquire resistance to DEX-mediated killing in conditions encountered in PCs including stimulation by toll-like receptor agonists and interactions with stromal cells. The resistant state was associated with impaired glucocorticoid receptor-mediated gene expression, autocrine activation of STAT3 through Janus Kinases (JAKs), and increased glycolysis. The JAK1/2 inhibitor ruxolitinib blocked STAT3-phosphorylation and partially improved DEX-mediated killing of stimulated CLL cells in vitro but not in CLL patients in vivo. An automated microscopy-based screen of a kinase inhibitor library implicated an additional protective role for the PI3K/AKT/FOXO pathway. Blocking this pathway with the glycolysis inhibitor 2-deoxyglucose (2-DG) or the PI3K-inhibitors idelalisib and buparlisib increased DEX-mediated killing but did not block STAT3-phosphorylation. Combining idelalisib or buparlisib with ruxolitinib greatly increased killing by DEX. These observations suggest that glucocorticoid resistance in CLL cells may be overcome by combining JAK and PI3K inhibitors.
Incorporating Knowledge Graph Embeddings into Topic Modeling

Probabilistic topic models could be used to extract low-dimension topics from document collections. However, such models without any human knowledge often produce topics that are not interpretable. In recent years, a number of knowledge-based topic models have been proposed, but they could not process fact-oriented triple knowledge in knowledge graphs. Knowledge graph embeddings, on the other hand, automatically capture relations between entities in knowledge graphs. In this paper, we propose a novel knowledge-based topic model by incorporating knowledge graph embeddings into topic modeling. By combining latent Dirichlet allocation, a widely used topic model with knowledge encoded by entity vectors, we improve the semantic coherence significantly and capture a better representation of a document in the topic space. Our evaluation results will demonstrate the effectiveness of our method.
Bankruptcy and Insolvency: An Exploration of Relevant Theories

The essence of the law on bankruptcy is to collect the debt of an entity and distribute such asset among the contending claimholders. It is, also meant to resolve the broad issues of business failure in the context of the imminent or indeed the actual collapse of the indebted entity. The objective of the study is to explore relevant theories guiding the procedure of distribution or entitlement in bankruptcy among a group of agents. The study employed exploratory research method via an extended literature review, to investigate the underlying principles guiding the allocation of a given amount of a perfectly divisible good among a group of agents. The results of this extended literature review indicate that the procedure of distribution or entitlement in bankruptcy is supported by five of the theories reviewed while only value based theory posits the absence of any cogent solution to the financial distress of the debtor. The knowledge of theories is not enough for business survival, the ability to predict the possible occurrence of business failures is necessary. Market based models including the stock market option valuation approach perform better than the earlier models which rely heavily on historical accounting figures.
Perceiving Gloss in Surfaces and Images

Color Appearance Models are successfully used to model the color perception differences seen when the same stimuli are presented on different media, e.g. hard copy or a self-luminous display. It is currently unknown if the similar effects are present in gloss perception and if there is need for Gloss Appearance Models. Gloss communication, and the higher level material appearance communication is becoming more important everyday with the increase in customized manufacturing and the need for the costumer to preview a final product while short-runs, time and cost constraints prohibit the use of hard-copy proofs. Three experiments are proposed in order to analyze this phenomenon. The Gloss matching performance of observers on real objects is first going to be studied. Then, the same experiment will be repeated with synthetic images. Finally, a cross-media matching experiment will be performed, where the observers will have to match a real material with synthetic representations. The same trend was observed in the experiment using only real objects and in the cross-media situation, where a high matching accuracy was obtained for low gloss samples, and the gloss of mid and high gloss samples was underestimated. The same accuracy for low gloss samples was obtained for the experiment with only synthetic images, but mid and high gloss samples were overestimated. The sensitivity of the observers was higher when only real samples were used, it decreased when the display was used due the lack of visual disparity and multiple viewing conditions, and it was lowest on the last experiment, influenced by the multiple media and the above limitations.
Capturing User Behavior in Subjective Quality Assessment of OTT Video Service

Customer satisfaction is an important factor governing adoption and retention of multimedia products and services, such as Over-The-Top(OTT) video transmission. Quality of Experience involves user-centric evaluation of various services. However, users differ in terms of their ratings of service quality. Some rating differences are due to unreliability (outlier users who are not motivated, or are not sensitive to differences in quality), but others are systematic differences in rating that may reflect different perspectives on quality. In this paper, we explore the use of outlier analysis and clustering as tools for interpreting QoE data. We report on experimental results demonstrating the use of outlier analysis and clustering. In interpreting the clusters, we examine users' opinions on different types of video disruption, and their ability to distinguish the different levels of impairments/failures.
Energy and economic considerations for ex-situ and aqueous mineral carbonation

Due to the scale and breadth of carbon dioxide emissions, and speculation regarding their impact on global climate, sequestration of some portion of these emissions has been under increased study. A practical approach to carbon sequestration will likely include several options, which will be driven largely by the energy demand and economics of operation. Aqueous mineral carbonation of calcium and magnesium silicate minerals has been studied as one potential method to sequester carbon dioxide. Although these carbonation reactions are all thermodynamically favored, they occur at geologic rates of reaction. Laboratory studies have demonstrated that these rates of reaction are accelerated with increasing temperature, pressure, and particle surface area. Mineral-specific activation methods were identified, however, each of these techniques incurs energy as well as economic costs. An overview of the mineral availability, pretreatment options and energy demands, and process economics is provided.