Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of f0 shape and phrasal position in Papuan Malay and American English word identification

Abstract The prosodic structure of under-researched languages in the Trade Malay language family is poorly understood. Although boundary marking has been uncontroversially shown as the major prosodic function in these languages, studies on the use of pitch accents to highlight important words in a phrase remain inconclusive. In addition, most knowledge of pitch accents is based on well-researched languages such as the ones from the Western-Germanic language family. This paper reports two word identification experiments comparing Papuan Malay with the pitch accent language American English, in order to investigate the extent to which the demarcating and highlighting function of prosody can be disentangled. To this end, target words were presented to native listeners of both languages and differed with respect to their position in the phrase (medial or final) and the shape of their f0 movement (original or manipulated). Reaction times for the target word identifications revealed overall faster responses for original and final words compared to manipulated and medial ones. The results add to previous findings on the facilitating effect of pitch accents and further improve our prosodic knowledge of underresearched languages.
Switch to Generalize: Domain-Switch Learning for Cross-Domain Few-Shot Classification

This paper considers few-shot learning under the cross-domain scenario. The cross-domain setting imposes a critical challenge, i.e. , using very few (support) samples to generalize the already-learned model to a novel domain. We hold a hypothesis, i.e. , if a deep model is capable to fast generalize itself to different domains (using very few samples) during training, it will maintain such domain generalization capacity for testing. It motivates us to propose a novel Domain-Switch Learning (DSL) framework. DSL embeds the cross-domain scenario into the training stage in a “fast switching” manner. Speciﬁcally, DSL uses a single domain for a training iteration and switches into another domain for the following iteration. During the switching, DSL enforces two constraints: 1) the deep model should not over-ﬁt the domain in the current iteration and 2) the deep model should not forget the already-learned knowledge of other domains. These two constraints jointly promote fast generalization across different domains. Experimental results conﬁrm that the cross-domain generalization capacity can be inherited from the training stage to the testing stage, validating our key hypothesis. Consequentially, DSL signiﬁcantly improves cross-domain few-shot classiﬁcation and sets up new state of the art.
Learning Unbiased Transformer for Long-Tail Sports Action Classification

The Sports Video Task in MediaEval 2021 Challenge contains two subtasks, detection and classification. The classification subtask aims to classify different strokes in table tennis segments. These strokes are fine grained actions and difficult to distinguish. To solve this challenge, we, the INF Team, proposed a fine grained action classification pipeline with SWIN-Transformer and a combination of optimization techniques. According to the evaluation results, our best submission ranks first with 74 . 21% accuracy and significantly outperforms the runner-up (74 . 21% v.s. 68 . 78%).
Lift and profile-drag characteristics of an NACA 0012 airfoil section as derived from measured helicopter-rotor hovering performance

Report presenting synthesized rotor-blade section lift and profile-drag characteristics for an NACA 0012 airfoil section as a function of angle of attack and Mach number for use in calculations of helicopter-rotor hovering performance are presented. At low tip Mach numbers, the synthesized data have higher maximum lift and lower profile drag at maximum lift than the equivalent two-dimensional airfoil data. Results regarding synthesized blade-section characteristics, rotor hovering characteristics, and rotor profile-drag torque are provided.
A New Perspective on "How Graph Neural Networks Go Beyond Weisfeiler-Lehman?"

We propose a new perspective on designing powerful Graph Neural Networks (GNNs). In a nutshell, this enables a general solution to inject structural properties of graphs into a message-passing aggregation scheme of GNNs. As a theoretical basis, we develop a new hierarchy of local isomorphism on neighborhood sub-graphs. Then, we theoretically characterize how message-passing GNNs can be designed to be more expressive than the Weisfeiler Lehman test. To elaborate this characterization, we propose a novel neural model, called GraphSNN , and prove that this model is strictly more expressive than the Weisfeiler Lehman test in distinguishing graph structures. We empirically verify the strength of our model on different graph learning tasks. It is shown that our model consistently improves the state-of-the-art methods on the benchmark tasks without sacriﬁcing computational simplicity and efﬁciency.
Explainable GNN-Based Models over Knowledge Graphs

Graph Neural Networks (GNNs) are often used to learn transformations of graph data. While effective in practice, such approaches make predictions via numeric manipulations so their output cannot be easily explained symbolically. We pro-pose a new family of GNN-based transformations of graph data that can be trained effectively, but where all predictions can be explained symbolically as logical inferences in Datalog—a well-known rule-based formalism. In particular, we show how to encode an input knowledge graph into a graph with numeric feature vectors, process this graph using a GNN
The P681H mutation in the Spike glycoprotein escapes IFITM restriction and is necessary for type I interferon resistance in the SARS-CoV-2 alpha variant

The appearance of new dominant variants of concern (VOCs) of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) threatens the global response to the COVID-19 pandemic. Of these, the alpha variant (also known as B.1.1.7) that appeared initially in the UK became the dominant variant in much of Europe and North America in the first half of 2021. The Spike (S) glycoprotein of alpha acquired seven mutations and two deletions compared to the ancestral virus, including the P681H mutation in the polybasic cleavage site that has been suggested to enhance S cleavage. Here, we show that the alpha S protein confers a level of resistance to the effects of interferon-β (IFNβ) in human lung epithelial cells. This correlates with resistance to an entry restriction mediated by interferon-induced transmembrane protein 2 (IFITM2) and a pronounced infection enhancement by IFITM3. Furthermore, the P681H mutation is essential for resistance to IFNβ and context-dependent resistance to IFITMs in the alpha S. However, while this appears to confer changes in sensitivity to endosomal protease inhibition consistent with enhanced cell-surface entry, its reversion does not reduce cleaved S incorporation into particles, indicating a role downstream of furin cleavage. Overall, we suggest that, in addition to adaptive immune escape, mutations associated with VOCs may well also confer replication and/or transmission advantage through adaptation to resist innate immune mechanisms. IMPORTANCE The emergence of Variants of Concern of SARS-CoV-2 has been a key challenge in the global response to the COVID-19 pandemic. Accumulating evidence suggests VOCs are being selected to evade the human immune response, with much interest focussed on mutations in the Spike protein that escape from neutralizing antibody responses. However, resistance to the innate immune response is essential for efficient viral replication and transmission. Here we show that the alpha (B.1.1.7) VOC of SARS-CoV-2 is substantially more resistant to type-1 interferons than the parental Wuhan-like virus. This correlates with resistance to the antiviral protein IFITM2, and enhancement by its paralogue IFITM3, that block virus entry into target cells. The key determinant of this is a proline to histidine change at position 681 in S adjacent to the furin-cleavage site that we have shown previously modulates IFITM2 sensitivity. Unlike other VOCs, in the context of the alpha spike, P681H modulates cell entry pathways of SARS-CoV-2, further reducing its dependence one endosomal proteases. Reversion of position 681 to a proline in viruses bearing the alpha spike is sufficient to restore interferon and IFITM2 sensitivity without reducing furin-mediated spike cleavage, suggesting post cleavage conformational changes in S are changing the viral entry pathway and therefore sensitivity to interferon. These data highlight the dynamic nature of the SARS CoV-2 S as it adapts to both innate and adaptive immunity in the human population.
Polynuclear ruthenium complexes are effective antibiotics against Pseudomonas aeruginosa

There is an urgent need to develop new antibiotics for the treatment of infections caused by drug-resistant Gram-negative bacteria. In particular, new and diverse chemical classes of antibiotics are needed, as most antibiotics in clinical development are derivatives of existing drugs. Despite a history of use as antimicrobials, metals and metal-based compounds have largely been overlooked as a source of new chemical matter for antibacterial drug discovery. In this work, we identify several ruthenium complexes, ruthenium red, Ru265, and Ru360’, that possess potent antibacterial activity against both laboratory and clinical isolates of Pseudomonas aeruginosa. Suppressors with increased resistance were sequenced and found to contain mutations in the mechanosensitive ion channel mscS-1 or the colRS two component system. The antibacterial activity of these compounds translated in vivo to Galleria mellonella larvae and mouse infection models. Finally, we identify strong synergy between these compounds and the antibiotic rifampicin, with a dose-sparing combination therapy showing efficacy in both infection models. Our findings provide clear evidence that these ruthenium complexes are effective antibacterial compounds against a critical priority pathogen and show promise for the development of future therapeutics.
High-Dose Paclitaxel and its Combination with CSF1R Inhibitor in Polymeric Micelles for Chemoimmunotherapy of Triple Negative Breast Cancer

The presence of immunosuppressive immune cells in cancer is a significant barrier to the generation of therapeutic immune responses. Similarly, in vivo triple-negative breast cancer (TNBC) models often contain prevalent tumor-associated macrophages in the tumor microenvironment (TME), resulting in breast cancer initiation, invasion, and metastasis by generating immunosuppressive environment. Here, we test systemic chemoimmunotherapy using small-molecule agents, paclitaxel (PTX), and colony-stimulating factor 1 receptor (CSF1R) inhibitor, PLX3397, to enhance the adaptive T cell immunity against TNBCs in immunocompetent mouse TNBC models. PTX and PLX3397 are very poorly soluble in water and shown poor therapeutic outcomes in TNBC animal models in conventional formulation. To address the challenge for the delivery of insoluble drugs to TNBC, we use high-capacity poly(2-oxazoline) (POx)-based polymeric micelles to greatly improve the solubility and widen the therapeutic index of such drugs. The results demonstrate that high-dose PTX in POx, even as a single agent, exerts strong effects on TME and induces the long-term immune memory. In addition, we demonstrate that the PTX and PLX3397 combination provides consistent therapeutic improvement across several TNBC models, resulting from the repolarization of the immunosuppressive TME and enhanced T cell immune response that suppress both the primary tumor growth and metastasis. Overall, the work emphasizes the benefit of drug reformulation and outlines potential translational path for both PTX and PTX with PLX3397 combination therapy using POx polymeric micelles for the treatment of TNBC.
Genetic Association of LDHA Variant g.2582481G>A with Racing Performance of Pakistani Pigeons

Pigeons are being used as a means of communication back in history due to their efficient flight stamina, navigational (homing) ability and endurance to harsh weather conditions. Due to these distinctive characteristics, pigeon racing and rearing has become a popular sport and hobby throughout the world, predominantly in Pakistan. The genetic tendency of LDHA gene in pigeons should be considered for understanding racing ability. The present study aimed to examine the genetic association of LDHA variant g.2582481G>A with racing performance in Pakistani pigeons. Our results demonstrated that 55% of the pigeon’s population was homozygous wild-type (G/G), 37.5% was heterozygous (G/A) and the remaining 7.5% was homozygous-mutant (A/A) at this locus. Furthermore, alternative allele frequencies within the best and low-performing cohorts of pigeons were 0.45 and 0.075 respectively. Furthermore, the Chi-Square association test was applied using PLINK data analysis toolset which showed a significant p-value of 1.381×10-4 with odds ratio (OR) of 10.09. Consequently, Pakistani pigeon population suggests a significant association of g.2582481G>A with racing performance similar to the other pigeon population of the world.
Termite diet rather than geographical origin determines the microbiome composition and functional genetic structure of nests from South American and African representatives, as revealed by a multiomics approach

Termites represent one of the most important insect groups worldwide due to their key role as plant decomposers and proxy of carbon recycling in the tropical rainforest ecosystems. Besides, high relevance in research has been given to these social insects due to a prominent role as urban pests. However, one of the most fascinating aspects of termites are their defence strategies that prevent the growth of detrimental microbiological strains on their nests. One success factor is the key role of the nest allied microbiome. Understanding how beneficial microbial strains aid termites in pathogen biocontrol strategies could provide us with an enhanced repertoire for fighting antimicrobial resistant strains or mine for genes for bioremediation purposes. We carried out a multiomics approach for dissecting the nest microbiome in a wide range of termite species, covering several feeding habits and three geographical locations at two tropical sides of the Atlantic Ocean, and an African savanna. Our experimental approach included untargeted volatile metabolomics, targeted evaluation of volatile naphthalene, taxonomical profile for bacteria and fungi through amplicon sequencing, and further dive into the genetic repertoire through a metagenomic sequencing approach. Volatile naphthalene was present in species belonging to the genera Nasutitermes and Cubitermes. We further assessed the apparent differences in terms of bacterial community structure, having found a stronger influence from feeding habits and genera, rather than the geographical location. Lastly, our metagenomic analysis revealed that the gene content provides both soil feeding genera with similar functional profiles, while the wood feeding genus shows a different one. These results seem to be independent of the geographical location, indicating that the nest functional profile is heavily influenced by the diet of the termite inhabiting, building, and maintaining the nest.
A comprehensive single cell data analysis of lymphoblastoid cells reveals the role of super‐enhancers in maintaining EBV latency

We probed the lifecycle of Epstein‐Barr virus (EBV) on a cell‐by‐cell basis using single cell RNA sequencing (scRNA‐seq) data from nine publicly available lymphoblastoid cell lines (LCLs). While the majority of LCLs comprised cells containing EBV in the latent phase, two other clusters of cells were clearly evident and were distinguished by distinct expression of host and viral genes. Notably, both were high expressors of EBV LMP1/BNLF2 and BZLF1 compared to another cluster that expressed neither gene. The two novel clusters differed from each other in their expression of EBV lytic genes, including glycoprotein gene GP350. The first cluster, comprising GP350–LMP1hi cells, expressed high levels of HIF1A and was transcriptionally regulated by HIF1‐α. Treatment of LCLs with Pevonedistat, a drug that enhances HIF1‐α signaling, markedly induced this cluster. The second cluster, containing GP350+LMP1hi cells, expressed EBV lytic genes. Host genes that are controlled by super‐enhancers (SEs), such as transcription factors MYC and IRF4, had the lowest expression in this cluster. Functionally, the expression of genes regulated by MYC and IRF4 in GP350+LMP1hi cells were lower compared to other cells. Indeed, induction of EBV lytic reactivation in EBV+ AKATA reduced the expression of these SE‐regulated genes. Furthermore, CRISPR‐mediated perturbation of the MYC or IRF4 SEs in LCLs induced the lytic EBV gene expression, suggesting that host SEs and/or SE target genes are required for maintenance of EBV latency. Collectively, our study revealed EBV‐associated heterogeneity among LCLs that may have functional consequence on host and viral biology.
Effects of seeding method, spacing and fertilizer on Chinese kale (Brassica alboglabra)

Two seeding methods, three spacings within 30 cm row and three forms of fertilizer were investigated on Chinese kale ('Kai Lan') in a factorial experiment. Transplanting at 2 weeks after sowing resulted in more vigorous plant growth and higher marketable fresh-weiqnt yield with greater mineral content than direct seeding. Decreasing plant spacing within the row from 30 cm to 20 cm and 10 cm resulted in a progressive increase in fresh-weight yield per hectare, due mainly to a greater number of plants per hectare. A combination, of cowdung and inorganic fertilizer was superior to inorganic fertilizer alone which in turn was superior to a commercial organic-inorganic fertilizer mixuture.
Insplico: Effective computational tool for studying intron splicing order genome-wide with short and long RNA-seq reads

Although splicing occurs largely co-transcriptionally, the order by which introns are removed does not necessarily follow the order in which they are transcribed. Whereas several genomic features are known to influence whether or not an intron is spliced before its downstream neighbour, multiple questions related to intron splicing order (ISO) remain unanswered. Here, we present Insplico, the first standalone tool to quantify ISO that works with both short and long read sequencing technologies. We first demonstrate its applicability and effectiveness recapitulating previously reported patterns, while unveiling overlooked biases associated with long read sequencing. We next show that ISO around individual exons is remarkably constant across cell and tissue types and even upon major spliceosomal disruption, and it is evolutionarily conserved between human and mouse brains. We also establish a set of universal features associated with ISO patterns across various animal and plant species. Finally, we used Insplico to investigate ISO in the context of tissue-specific exons, particularly focusing on SRRM4-dependent microexons. We found that the majority of such microexons have non-canonical ISO, in which the downstream intron is spliced first, and we revealed two potential modes of SRRM4 regulation of microexons related to their ISO and various splicing-related features. Insplico is available on gitlab.com/aghr/insplico.
A cell-autonomous role for primary cilia in long-range commissural axon guidance

Ciliopathies are characterized by the absence or dysfunction of primary cilia. Despite the fact that cognitive impairments are a common feature of ciliopathies, how cilia dysfunction affects neuronal development has not been characterized in detail. Here, we show that the primary cilium is required cell-autonomously by neurons during neural circuit formation. In particular, the primary cilium is crucial during axonal pathfinding for the switch in responsiveness of axons at a choice point, or intermediate target. Utilizing animal models and in vivo, ex vivo, as well as in vitro experiments, we provide evidence for a critical role of the primary cilium in long-range axon guidance. The primary cilium on the cell body of commissural neurons transduces long-range guidance signals sensed by growth cones navigating an intermediate target. In extension of our finding that Shh is required for the rostral turn of post-crossing commissural axons, we show here that the cilium is required for a transcriptional change of axon guidance receptors, which in turn mediate the repulsive response to floorplate-derived Shh shown by post-crossing commissural axons.
The host transcriptional response to superinfection by influenza virus and streptococcus pneumonia

Secondary bacterial challenges during influenza virus infection (‘superinfection’) cause excessive mortality and hospitalization. Here we present a longitudinal study of gene-expression changes in murine lungs during superinfection, with an initial influenza A virus (IAV) infection and a subsequent Streptococcus pneumonia (SP) infection. In addition to the well-characterized impairment of the innate immune response, we identified superinfection-specific alterations in endothelial-related genes, including a previously uncharacterized rapid downregulation of particular angiogenic and vascular markers. Superinfection-specific alterations were also evident in the analysis of cellular states related to the host’s immune resistance against pathogens. We found that superinfected mice manifested an excessive rapid induction of immune resistance starting only a few hours after the secondary bacterial challenge. In addition, there was a substantial rewiring of the resistance program: interferon-regulated genes were switched from positive to negative correlations with resistance, whereas genes of fatty-acid metabolism were switched from negative to positive correlations with resistance. Thus, the transcriptional resistance state in superinfection is reprogrammed toward repressed interferon signaling and induced fatty acid metabolism. Our findings suggest new insights into the remodeling of the host defense upon superinfection, providing promising targets for future therapeutic interventions.
Loss of Retinogeniculate Synaptic Function in the DBA/2J Mouse Model of Glaucoma

Abstract Retinal ganglion cell (RGC) axons comprise the optic nerve and carry information to the dorsolateral geniculate nucleus (dLGN), which is then relayed to the cortex for conscious vision. Glaucoma is a blinding neurodegenerative disease that commonly results from intraocular pressure (IOP)-associated injury leading to RGC axonal pathology, disruption of RGC outputs to the brain, and eventual apoptotic loss of RGC somata. The consequences of elevated IOP and glaucomatous pathology on RGC signaling to the dLGN are largely unknown yet are likely to contribute to vision loss. Here, we used anatomic and physiological approaches to study the structure and function of retinogeniculate (RG) synapses in male and female DBA/2J (D2) mice with inherited glaucoma before and after IOP elevation. D2 mice showed progressive loss of anterograde optic tract transport to the dLGN and vGlut2 labeling of RGC axon terminals while patch-clamp measurements of RG synaptic function showed that synaptic transmission was reduced in 9-month and 12-month D2 mice because of the loss of individual RGC axon inputs. TC neuron dendrites had reduced Sholl complexity at 12 months, suggestive of delayed reorganization following reduced synaptic input. There was no detectable change in RGC density in 11- to 12-month D2 retinas, quantified as the number of ganglion cell layer-residing somata immuno-positive for NeuN and immuno-negative for the amacrine marker choline acetyltransferase (ChAT). Thus, observed synaptic defects appear to precede RGC somatic loss. These findings identify glaucoma-associated and IOP-associated deficits in an important subcortical RGC projection target, shedding light on processes linking IOP to vision loss.