Miracle-dz/UniFAR-FTUs huggingface dataset:
Why Am I Not Seeing It? Understanding Users’ Needs for Counterfactual Explanations in Everyday Recommendations

Intelligent everyday applications typically rely on automated Recommender Systems (RS) to generate recommendations that help users make decisions among a large number of options. Due to the increasing complexity of RS and the lack of transparency in its algorithmic decision-making, researchers have recognized the need to support users with explanations. While many traditional Explainable AI methods fall short in disclosing the internal intricacy of recommender systems, counterfactual explanations provide many desirable explainable features by offering human-like explanations that contrast an existing recommendation with alternatives. However, there is a lack of empirical research in understanding users’ needs of counterfactual explanations in their usage of everyday intelligent applications. In this paper, we investigate whether and when to provide counterfactual explanations to support people’s decision-making with everyday recommendations through a question-driven approach. We conducted a preliminary survey study and an interview study to understand how existing explanations might be insufficient to support users and elicit the triggers that prompt them to ask why not questions and seek additional explanations. The findings reveal that the utility of decision is a primary factor that may affect their counterfactual information needs. We then conducted an online scenario-based survey to quantify the correlation between utility and explanation needs and found significant correlations between the measured variables.
Building a Shared Conceptual Model of Complex, Heterogeneous Data Systems: A Demonstration

The world of data objects and systems is complex and heterogeneous, making collaboration across tools, teams, and institutions difficult. Important goals like effective data science, responsible data governance, and well-informed data consumption all require participation from multiple parties who share conceptual data models despite being unfamiliar with, or organizationally distant from each other. In order to be productive together, data collaborators need a shared conceptual model that includes traditional schemas and system models, such as pipelines and procedures. This shared model does not have to be entirely correct, but to enable effective collaboration, it should be tool, team, and institution-independent. We describe a working demonstration system that aims to build this shared conceptual model. This system borrows ideas from knowledge graphs and other massive collaborative efforts to curate data artifacts beyond the reach of any one person or institution.
A study on the use of 3rd party DNS resolvers for malware filtering or censorship circumvention

DNS resolvers perform the essential role of translating domain names into IP addresses. The default DNS resolver oﬀered by an Internet Service Provider (ISP) can be undesirable for a number of reasons such as censorship, lack of malware ﬁltering options and low service quality. In this paper, we propose a novel method for estimating the amount of DNS traﬃc directed at non-ISP resolvers by using DNS and NetFlow data from an ISP. This method is extended to also estimate the amount of DNS traﬃc towards resolvers that oﬀer malware ﬁltering or parental control functionality. Finally, we propose a novel method for estimating the amount of DNS traﬃc at non-ISP resolvers that would have been censored by ISP resolvers. The results of applying these methods on an ISP dataset shows to which extent 3rd party resolvers are chosen by users for either malware ﬁltering or censorship circumvention purposes.
Photon: A High-Performance Query Engine for the Lakehouse

We present Photon, a new native vectorized query engine powering the Databricks Runtime. Photon achieves state-of-the-art query execution times and industry-leading price performance on real workloads against data stored in the Parquet and Delta format, in situ over data lakes such as Amazon S3, ADLS, and GCS. Photon supports not only SQL but also the DataFrame APIs of Apache Spark [3], PySpark, and Koalas. We developed Photon in response to the observation that organizations are shifting to a new paradigm called the Lakehouse [2], which combines the low cost, open access, and versatility of data lakes with the reliability, performance, and governance features of data warehouses. One reason for this trend is that the majority of enterprise data today (over 90% of bytes, in our experience) is already stored in data lakes. Users have reported that it is time-consuming and error-prone to copy and maintain subsets of this data in an exter-nal data warehouse while maintaining data freshness and accuracy. Instead, the Lakehouse enables applications to operate on the data in-situ throughout the data lifecycle (e.g., from raw ingested values to bronze/silver/golden) without compromising on fidelity or performance. The full data lineage can be tracked and errors can be corrected from the raw source data.
Funnel Control for a Class of High-Order Nonlinear Systems

This paper addresses the problem of funnel output tracking control for a class of unknown high-order nonlinear systems with state feedbacks, which requires to achieve output tracking with prescribed accuracy when both the system nonlinearities and the powers of the system are unknown. Therefore, a robust funnel control algorithm, i.e., a continuous, static, universal, statefeedback controller is explicitly constructed, which ensures that the state errors evolve within the predesigned performance space. The advantages of the proposed funnel output tracking controller when compared with the current approaches lie in the fact that no a priori knowledge of system nonlinearities, including generally required bounding functions, is needed. Furthermore, all the powers in each high-order subsystem are not required to be known as well. A simulation example is provided to demonstrate the effectiveness of the proposed algorithm. Keywords–nonlinear systems; output tracking; funnel control; unstabilizable linearization.
The 3D Hash Join: Building On Non-Unique Join Attributes

One of the most prominent ways to evaluate an equi-join is based on hashing. We consider the problem of non-unique join attributes on the build side. In conventional hash tables where collisions are resolved by chaining, duplicates inevitably lead to long collision chains. This causes a high number of expensive main memory accesses and join predicate evaluations during the probe phase, increasing the runtime of the overall join. A related problem occurs when the query optimizer cannot determine the uniqueness of the join attribute of the build side. We present the 3D Hash Join to efficiently evaluate main-memory hash joins in the presence of duplicate build keys and skew. The main idea is to cluster the hash table collision chains based on the distinct values of the build attribute. We further introduce a technique called deferred unnesting to speed up the evaluation of multiple joins. In an experimental comparison with an implementation of a chaining hash table, our approach achieves a speedup of up to a factor of 3 . 53 for a single key/foreign key join and 5 . 67 for many-to-many joins.
Nuclear fascin regulates cancer cell survival

Fascin is an important regulator of F-actin bundling leading to enhanced filopodia assembly. Fascin is also overexpressed in most solid tumours where it supports invasion through control of F-actin structures at the periphery and nuclear envelope. Recently fascin has been identified in the nucleus of a broad range of cell types but the contributions of nuclear fascin to cancer cell behaviour remain unknown. Here we demonstrate that fascin bundles F-actin within the nucleus to support chromatin organisation and efficient DNA damage response. Fascin associates directly with phosphorylated Histone H3 leading to regulated levels of nuclear fascin to support these phenotypes. Forcing nuclear fascin accumulation through the expression of nuclear-targeted fascin-specific nanobodies or inhibition of Histone H3 kinases results in enhanced and sustained nuclear F-actin bundling leading to reduced invasion, viability and nuclear fascin-specific/driven apoptosis. These findings represent an additional important route through which fascin can support tumorigenesis and provide insight into potential pathways for targeted fascin-dependent cancer cell killing.
cAMP−EPAC−PKCε−RIM1α signaling regulates presynaptic long-term potentiation and motor learning

The cerebellum is involved in learning of fine motor skills, yet whether presynaptic plasticity contributes to such learning remains elusive. Here, we report that the EPAC-PKCε module has a critical role in a presynaptic form of long-term potentiation in the cerebellum and motor behavior in mice. Presynaptic cAMP−EPAC−PKCε signaling cascade induces a previously unidentified threonine phosphorylation of RIM1α, and thereby initiates the assembly of the Rab3A−RIM1α−Munc13-1 tripartite complex that facilitates docking and release of synaptic vesicles. Granule cell-specific blocking of EPAC−PKCε signaling abolishes presynaptic long-term potentiation at the parallel fiber to Purkinje cell synapses and impairs basic performance and learning of cerebellar motor behavior. These results unveil a functional relevance of presynaptic plasticity that is regulated through a novel signaling cascade, thereby enriching the spectrum of cerebellar learning mechanisms.
Discovery of a broadly-neutralizing human antibody that can rescue mice challenged with neurotoxin-rich snake venoms

Snakebite envenoming continues to claim many lives across the globe, necessitating the development of improved therapies. To this end, human monoclonal antibodies may possess advantages over current plasma-derived antivenoms by offering superior safety and improved neutralization capacity. However, as new antivenom products may need to be polyvalent, i.e., target multiple different snake species, without dramatically increasing dose or cost of manufacture, such monoclonal antibodies need to be broadly-neutralizing. Here, we report the establishment of a pipeline for the discovery of high affinity broadly-neutralizing human monoclonal antibodies. We further demonstrate its utility by discovering an antibody that can prevent lethality induced by N. kaouthia whole venom at an unprecedented low molar ratio of one antibody per toxin, and which also prolongs survival of mice injected with Dendroaspis polylepis or Ophiophagus hannah whole venoms.
Composite mutations give an extra insight into epistasis

The intricate genotype-phenotype relationship has been a long-standing issue in biology, important both from the fundamental and applied points of view. One of the major irregularities hindering progress in establishing these links is epistasis – the complex and elusive interaction between mutations. Despite the vast accumulated genetic data and progress in this area, epistasis is still far from being completely understood. Epistasis can be studied quantitatively in combinatorially complete datasets, which form hypercubes in protein sequence space, where connected sequences are one mutation away from each other. However, this might be insufficient to portray the full picture of epistatic interactions. To extend the repertoire of the methods for exploring epistasis, we propose here to consider hyperrectangles, where some edges connect sequences being two or more mutations away from each other. The present work formalizes the theoretical knowledge about these novel structures and compares the amount of epistasis identified in hypercubes and hyperrectangles constructed from experimental datasets. A new algorithm, CuboidME, was developed for calculating hyperrectangles, which were then compared to hypercubes. In the experimental datasets, there were four orders of magnitude more hyperrectangles than hypercubes for the same sample size. Subsequently, we showed that for the studied datasets there is an increase in epistasis measured by epistatic coefficients in hyperrectangles compared to hypercubes. For the same datasets, hyperrectangles could find more sign epistasis than using hypercubes alone. We also show that there is a trend for increase in epistasis with increasing number of mutations being considered in a hyperrectangle. The results indicate that hyperrectangles can be used to reveal more information on epistasis in a fitness landscape, especially if it is combinatorially incomplete.
Understanding molecular mechanisms and predicting phenotypic effects of pathogenic tubulin mutations

Cells rely heavily on microtubules for several processes, including cell division and molecular trafficking. Mutations in the different tubulin-α and -β proteins that comprise microtubules have been associated with various diseases and are often dominant, sporadic and congenital. While the earliest reported tubulin mutations affect neurodevelopment, mutations are also associated with other disorders such as bleeding disorders and infertility. We performed a systematic survey of tubulin mutations across all isotypes in order to improve our understanding of how they cause disease, and increase our ability to predict their phenotypic effects. Both protein structural analyses and computational variant effect predictors were very limited in their utility for differentiating between pathogenic and benign mutations. This was even worse for those genes associated with non-neurodevelopmental disorders. We selected tubulin-α and -β disease mutations that were most poorly predicted for experimental characterisation. These mutants co-localise to the mitotic spindle in HeLa cells, suggesting they may exert dominant-negative effects by altering microtubule properties. Our results show that tubulin mutations represent a blind spot for current computational approaches, being much more poorly predicted than mutations in most human disease genes. We suggest that this is likely due to their strong association with dominant-negative and gain-of-function mechanisms.
The Prmt5-Vasa module is essential for dichotomous spermatogenesis in Bombyx mori

Spermatogenesis is a key process for the sexual reproduction species. In lepidopteran insects, dichotomous spermatogenesis is a notable feature, which produces eupyrene (nucleate) and apyrene (anucleate) spermatozoa. Both sperm morphs are essential for fertilization, as eupyrene sperm fertilizes the egg, while apyrene sperm is necessary for eupyrene sperm migration. In Drosophila, Prmt5 acts as a type II arginine methyltransferase to catalyze the symmetrical dimethylation of arginine residues (sDMA) in Vasa. However, Prmt5 is involved in regulating spermatogenesis, but Vasa is not. To date, the functional genetic study on dichotomous spermatogenesis in the lepidopteran model Bombyx mori has been limited, thus the underlying mechanism remains largely unknown. In this study, we report that both BmPrmt5 and BmVasa act as essential components in the regulation of dichotomous spermatogenesis in Bombyx mori. The loss-of-function mutants of BmPrmt5 (ΔBmPrmt5) and BmVasa (ΔBmVasa) derived from CRISPR/Cas9-based gene editing show similar male and female-sterile phenotypes. Through immunofluorescence staining analysis, we found that the morphs of both ΔBmPrmt5 and ΔBmVasa sperm show severe defects, indicating an essential role for both BmPrmt5 and BmVasa in the regulation of dichotomous spermatogenesis. RNA-seq analyses indicate that the defects in dichotomous spermatogenesis observed for ΔBmPrmt5 and ΔBmVasa mutants could be attributed to the reduced expression of the spermatogenesis-related genes including Sex-lethal (BmSxl), implying that BmSxl may act downstream of Prmt5 and Vasa in regulating apyrene sperm development. These findings suggest that BmPrmt5 and BmVasa constitute an integral regulatory module essential for dichotomous spermatogenesis in Bombyx mori, in which BmPrmt5 may promote BmVasa activity through sDMA modification. Author Summary Dichotomous spermatogenesis is a notable feature in Lepidoptera insects, in which a single male produces nucleated and anucleated dimorphic sperm. Both sperm morphs are essential for fertilization, as the eupyrene sperm fertilizes the egg, while the apyrene sperm assists in transporting the eupyrene sperm to the female sperm storage organs. To date, the mechanism of dichotomous spermatogenesis is still unclear, as very limited components participating in this process have been reported. Here we defined the function of BmPrmt5 (Protein arginine methyltransferase 5) and its substrate BmVasa in dichotomous spermatogenesis in the lepidopteran insect Bombyx mori. Our genetic analyses revealed that both BmPrmt5 and BmVasa are essential for dichotomous spermatogenesis. Moreover, RNA-seq analyses, in conjunction with the genetic and immunofluorescence staining analyses, suggest a potential regulatory pathway consisting of the BmPrmt5–BmVasa module in dichotomous spermatogenesis in Bombyx mori. This study expands the knowledge of reproduction biology in insects, and may provide potential gene targets for pest control.
Publication games: In the web of reciprocity

The present processes of research assessment, i.e. focusing on one or a few, related, sciento-metrics, foster questionable authorship practices, like gifting authorship to non-contributing people. An especially harmful one of these unethical practices is the formation of publication cartels, where authors offer gift authorship to each other reciprocally. Here, by developing a simple model and a simulation of the publication process I investigate how beneficial cartels can be and what measure can be used to restrict them. My results indicate that publication cartels can significantly boost members’ productivity even if paper counts are weighted by the inverse of author number (the 1/n rule). Nevertheless, applying the 1/n rule generates conflicts of interest both among cartel members themselves and between members and non-members which might lead to the self-purification of the academic publishing industry.
PhaseTypeR: phase-type distributions in R with reward transformations and a view towards population genetics

Phase-type distributions are a general class of models that are traditionally used in actuarial sciences and queuing theory, and more recently in population genetics. A phase-type distributed random variable is the time to absorption in a discrete or continuous time Markov chain on a finite state space with an absorbing state. The R package PhaseTypeR contains all the key functions—mean, (co)variance, probability density function, cumulative distribution function, quantile function, random sampling and reward transformations—for both continuous (PH) and discrete (DPH) phase-type distributions. Additionally, we have also implemented the multivariate continuous case (MPH) and the multivariate discrete case (MDPH). We illustrate the usage of PhaseTypeR in simple examples from population genetics (e.g. the time until the most recent common ancestor or the total number of mutations in an alignment of homologous DNA sequences), and we demonstrate the power of PhaseTypeR in more involved applications from population genetics, such as the coalescent with recombination and the structured coalescent. The multivariate distributions and ability to reward-transform are particularly important in population genetics, and a unique feature of PhaseTypeR.
The requirement of GW182 in miRNA-mediated gene silencing in Drosophila larval development

microRNAs (miRNAs) regulate a wide variety of biological processes by silencing their target genes. Argonaute (AGO) proteins load miRNAs to form RNA-induced silencing complex (RISC), which mediates translational repression and/or mRNA decay of the targets. A scaffold protein called GW182 directly binds AGO and the CCR4-NOT deadenylase complex, initiating the mRNA decay reaction. Although previous studies have demonstrated the critical role of GW182 in cultured cells as well as in cell-free systems, its biological significance in living organisms remains poorly explored, especially in Drosophila melanogaster. Here, we generated gw182-null flies using the CRISPR/Cas9 system and found that, unexpectedly, they can survive until an early second instar larval stage. Moreover, in vivo miRNA reporters can be effectively repressed even in the absence of GW182. Nevertheless, gw182-null flies have defects in the expression of chitin-related genes and the formation of the larval trachea system, preventing them to complete the larval development. Our results highlight the importance of both GW182-dependent and -independent silencing mechanisms in vivo.
Cytokine and phenotypic cell profiles in human cutaneous leishmaniasis caused by Leishmania donovani

Background The innate immune mediators are likely to influence the clinical phenotype of leishmaniasis by primary responses which limit or facilitate the spread of the parasite, as well as by modulating adaptive immunity. This study investigated the response of key innate immune cells in a focus which regularly reports localised cutaneous leishmaniasis (LCL) caused by Leishmania donovani, a species which typically causes visceral disease. Methods Peripheral blood mononuclear cell (PBMC) derived macrophage and dendritic cell responses to soluble Leishmania antigen (SLA) were compared between patients with LCL and healthy controls from endemic and non-endemic areas. Inflammatory mediators produced by macrophages (TNF-α, NO, TGF-β and IL-10) and dendritic cells (IL-12p70, IL-10) and cell surface markers of macrophage polarization, activation and maturation were determined at 24h, 48h and 72h by Enzyme-linked immunosorbent assay (ELISA) and flowcytometry. Results Patient derived macrophages and dendritic cells produced higher levels of both pro and anti-inflammatory mediators compared to controls (p<0.05) with the best discrimination for active disease observed at 72h. Data demonstrated an early activation of macrophages and a subsequent pro-inflammatory bias, as indicated by temporal profiles of TNF-α/TGF-β and TNF-α/IL-10 ratios and higher proportions of classical (M1) macrophages. Higher TGF-β levels were observed in cells from patients with ulcerated or persistent lesions. Immune responses by cells derived from controls in endemic and non-endemic regions did not differ significantly from each other. Conclusions The overall immunophenotypic profile suggests that LCL observed in the country is the result of a balancing immune response between pro-inflammatory and regulatory mediators. The mediators which showed distinct profiles in patients warrant further investigation as potential candidates for immunotherapeutic approaches. A comparison with visceral leishmaniasis caused by the same species, would provide further evidence on the differential role of these mediators in the resulting clinical phenotype.