Miracle-dz/UniFAR-FTUs huggingface dataset:
TreeSLS: A Whole-system Persistent Microkernel with Tree-structured State Checkpoint on NVM

Whole-system persistence promises simplified application deployment and near-instantaneous recovery. This can be implemented using single-level store (SLS) through periodic checkpointing of ephemeral state to persistent devices. However, traditional SLSs suffer from two main issues on checkpointing efficiency and external synchrony, which are critical for low-latency services with persistence need. In this paper, we note that the decentralized state of microkernel-based systems can be exploited to simplify and optimize state checkpointing. To this end, we propose TreeSLS, a whole-system persistent microkernel that simplifies the whole-system state maintenance to a capability tree and a failure-resilient checkpoint manager. TreeSLS further exploits the emerging non-volatile memory to minimize checkpointing pause time by eliminating the distinction between ephemeral and persistent devices. With efficient state maintenance, TreeSLS further proposes delayed external visibility to provide transparent external synchrony with little overhead. Evaluation on microbenchmarks and real-world applications (e.g., Memcached, Redis and RocksDB) show that TreeSLS can complete a whole-system persistence in around 100 μs and even take a checkpoint every 1 ms with reasonable overhead to applications.
Mapping the molecular motions of 5-HT3 serotonin-gated channel by Voltage-Clamp Fluorometry

The serotonin-gated ion channel (5-HT3R) mediates excitatory neuronal communication in the gut and the brain. It is the target for setrons, a class of competitive antagonists widely used as antiemetics, and is involved in several neurological diseases. Cryo-electron microscopy of the 5-HT3R in complex with serotonin or setrons revealed that the protein has access to a wide conformational landscape. However, assigning known high-resolution structures to actual states contributing to the physiological response remains a challenge. In the present study, we used voltage-clamp fluorometry (VCF) to measure simultaneously, for 5-HT3R expressed at a cell membrane, conformational changes by fluorescence and channel opening by electrophysiology. Four positions identified by mutational screening report motions around and outside the serotonin-binding site through incorporation of cysteine-tethered rhodamine dyes with or without a nearby quenching tryptophan. VCF recordings show that the 5-HT3R has access to four families of conformations endowed with distinct fluorescence signatures: “resting-like” without ligand, “inhibited-like” with setrons, “pre-active-like” with partial agonists and “active-like” (open channel) with partial and strong agonists. Data are remarkably consistent with cryo-EM structures, the fluorescence partners matching respectively Apo, setron-bound, 5-HT bound-closed and 5-HT-bound-open conformations. Data show that strong agonists promote a concerted motion of all fluorescently labelled sensors during activation, while partial agonists, especially when loss-of-function mutations are engineered, stabilize both active and pre-active conformations. In conclusion, VCF, though the monitoring of electrophysiologically silent conformational changes, illuminates allosteric mechanisms contributing to signal transduction and their differential regulation by important classes of physiological and clinical effectors. Significance Statement High-resolution structures of serotonin-gated receptors (5-HT3AR) have evidenced a wide range of conformations that are challenging to annotate to physiologically relevant states. Voltage-clamp fluorometry allows to investigate the activation of 5-HT3AR by simultaneously following molecular motions and electrophysiological states at the plasma membrane. Here, we developed four fluorescent sensors reporting conformational changes at the serotonin binding site and at the extracellular domain and transmembrane domain interface. Investigation of a series of agonists, partial agonists and antagonists show that strong agonists promote a concerted motion of the whole protein during activation, while antagonists and partial agonists stabilize distinct closed-channel conformations. Data offer insights into allosteric mechanisms, unravelling the conformational dynamics of the receptors and helping to annotate high-resolution static structures.
Targeting EIF4A triggers an interferon response to synergize with chemotherapy and suppress triple-negative breast cancer

Protein synthesis is frequently dysregulated in cancer and selective inhibition of mRNA translation represents an attractive cancer therapy. Here, we show that therapeutically targeting the RNA helicase eIF4A by Zotatifin, the first-in-class eIF4A inhibitor, exerts pleiotropic effects on both tumor cells and the tumor immune microenvironment in a diverse cohort of syngeneic triple-negative breast cancer (TNBC) mouse models. Zotatifin not only suppresses tumor cell proliferation but also directly repolarizes macrophages towards an M1-like phenotype and inhibits neutrophil infiltration, which sensitizes tumors to immune checkpoint blockade. Mechanistic studies revealed that Zotatifin reprograms the tumor translational landscape, inhibits the translation of Sox4 and Fgfr1, and induces an interferon response uniformly across models. The induction of an interferon response is partially due to the inhibition of Sox4 translation by Zotatifin. A similar induction of interferon-stimulated genes was observed in breast cancer patient biopsies following Zotatifin treatment. Surprisingly, Zotatifin significantly synergizes with carboplatin to trigger DNA damage and an even heightened interferon response resulting in T cell-dependent tumor suppression. These studies identified a vulnerability of eIF4A in TNBC, potential pharmacodynamic biomarkers for Zotatifin, and provide a rationale for new combination regimens comprising Zotatifin and chemotherapy or immunotherapy as treatments for TNBC. One Sentence Summary Targeting EIF4A sensitizes TNBC to immune therapy and chemotherapy by suppressing Sox4, inducing an interferon response, and reprograming the tumor immune microenvironment.
Requirement of microtubules for secretion of a micronemal protein CpTSP4 in the invasive stage of the apicomplexan Cryptosporidium parvum

The zoonotic Cryptosporidium parvum is a global contributor to infantile diarrheal diseases and opportunistic infections in immunocompromised/weakened individuals. Like other apicomplexans, it possesses several specialized secretory organelles, including micronemes, rhoptry and dense granules. However, the understanding of cryptosporidial micronemal composition and secretory pathway remains limited. Here we report a new micronemal protein in C. parvum, namely thrombospondin repeat domain-containing protein-4 (CpTSP4), providing insights into these ambiguities. Immunostaining and enzyme-linked assays show that CpTSP4 is prestored in the micronemes of unexcysted sporozoites but secreted during sporozoite excystation, gliding and invasion. In excysted sporozoites, CpTSP4 is also distributed on the two central microtubules unique to Cryptosporidium. The secretion and microtubular distribution could be completely blocked by selective kinesin-5 inhibitors, SB-743921 and SB-715992, resulting in the accumulation of CpTSP4 in micronemes. These support the kinesin-dependent microtubular trafficking of CpTSP4 for secretion. We also localize γ-tubulin, consistent with kinesin-dependent anterograde trafficking. Additionally, recombinant CpTSP4 displays nanomolar binding affinity to host cell surface, for which heparin acts as one of the host ligands. A novel heparin-binding motif is identified and biochemically validated for its contribution to the adhesive property of CpTSP4 by peptide competition assays and site-directed mutagenesis. These findings shed light on the mechanisms of intracellular trafficking and secretion of a cryptosporidial micronemal protein and the interaction of a TSP-family protein with host cells. Importance Cryptosporidium parvum is a globally distributed apicomplexan parasite infecting humans and/or animals. Like other apicomplexans, it possesses specialized secretory organelles in the zoites, in which micronemes discharge molecules to facilitate the movement and invasion of zoites. Although past and recent studies have identified several proteins in cryptosporidial micronemes, our understanding on the composition, secretory pathways and domain-ligand interactions of micronemal proteins remains limited. This study identifies a new micronemal protein, namely CpTSP4, that is discharged during excystation, gliding and invasion of C. parvum sporozoites. The CpTSP4 secretion depends on the intracellular trafficking on the two Cryptosporidium-unique microtubes that could be blocked by kinesin-5/Eg5 inhibitors. Additionally, a novel heparin-binding motif is identified and biochemically validated, which contributes to the nanomolar binding affinity of CpTSP4 to host cells. These findings indicate that kinesin-dependent microtubular trafficking is critical to CpTSP4 secretion and heparin/heparan sulfate is one of the ligands for this micronemal protein.
Exploring the Influence of Sensory Marketing on Brand Perception

Abstract The main purpose of this paper is to investigate how the number, perceived intensity, and frequency of sensory involvement in the consumer-brand relationship, impact brand perception. The research was conducted on a sample of 189 respondents from the Republic of Croatia. To test the hypotheses factor and regression analyses were used. The main findings of this research are: a) involvement of multiple senses in the consumer-brand relationship has a positive effect on brand perception; b) the greater the frequency of involving multiple senses in the consumer-brand relationship, the more positive effect it has on brand perception; and c) the higher intensity of sensory involvement in the consumer-brand relationship does not have a significant effect on brand perception. This research contributes to marketing and brand management literature by investigating importance of sensory marketing, more specifically number, perceived intensity, and frequency of sensory involvement on brand perception.
Fungal Pathogen Gene Selection for Predicting the Onset of Infection Using a Multi-Stage Machine Learning Approach

Phytopathogenic fungi pose a serious threat to global food security. Next-generation sequencing technologies, such as transcriptomics, are increasingly used to profile infection, assess environmental adaptation and gauge host-responses. The accumulation of these large-scale data has created the opportunity to employ new computational methods to gain greater biological insights. Machine learning approaches, that learn to identify patterns in complex data sets, have recently been applied to the field of plant-pathogen interactions. Here, we apply a machine learning approach to transcriptomics data for the fungal pathogen Zymoseptoria tritici, to predict the onset of infection as measured by timing of the appearance of necrosis. We present a method for identifying the most important genes that predict infection timings, accurately classify isolates as early and late infectors and predict the timing of infection of ‘novel’ isolates using only a subset of the data. These methods and the genes identified further demonstrate the use of these tools in the field of plant-pathogen interactions and have implications for the identification of biomarkers for disease monitoring and forecasting. Fungi that infect plants pose a serious threat to global food security. Methods to study these pathogens generate vast amounts of data that create new opportunities for computational tools to analyse them. Machine learning methods can learn patterns in complex data such as when genes are turned on or off in fungal plant pathogens. In this study we use machine learning approaches to predict the onset of infection in several isolates of an important fungal pathogen. We show that these methods can identify a small group of genes that are predictive of the infection onset. We can even use these methods on ‘novel’ isolates to infer the likely timing of disease development. Our work has implications for plant disease diagnosis, monitoring and forecasting.
Patterns of Cerebellar-Cortical Structural Covariance Mirror Anatomical Connectivity of Sensorimotor and Cognitive Networks

The cortex and cerebellum are densely connected through reciprocal input/output projections that form segregated loop circuits. Anatomical studies in primates and imaging studies in humans show that anterior lobules of the cerebellum exhibit denser connections to sensorimotor and parietal cortical regions, while lobules Crus I and II are more heavily connected to prefrontal regions. The cerebellum and cortex develop in tandem in childhood, leading to the hypothesis that individual differences in structure should be related, especially for connected regions. To test this hypothesis we examined covariation between the volumes of anterior sensorimotor and lateral cognitive lobules of the cerebellum and measures of cortical thickness (CT) and surface surface area (SA) across the whole brain in a sample of 270 young, healthy adults drawn from the HCP dataset. We found that patterns of cerebellar-cortical covariance differed between sensorimotor and cognitive networks such that anterior motor lobules of the cerebellum showed greater covariance with sensorimotor regions of the cortex, while lobules Crus I and Crus II showed greater covariance with frontal and temporal regions. Interestingly, cerebellar volume showed predominantly negative relationships with CT and predominantly positive relationships with SA. Individual differences in SA are thought to be largely under genetic control while CT is thought to be more malleable by experience. This suggests that cerebellar-cortical covariation for SA may be a more stable feature, whereas covariation for CT may be more affected by development. Additionally, dissimilarity metrics revealed that the pattern of covariance showed a gradual transition between sensorimotor and cognitive lobules, consistent with evidence of functional gradients within the cerebellum. Taken together, these findings are consistent with known patterns of structural and functional connectivity between the cerebellum and cortex. They also shed new light on possibly differing relationships between cerebellar volume and cortical thickness and surface area. Finally, our findings are consistent with the interactive specialization framework which proposes that structurally and functionally connected brain regions develop in concert.
Ensemble Method via Ranking Model for Conversational Modeling with Subjective Knowledge

This paper describes our submission to the fifth track of the 11th Dialog System Technology Challenge (DSTC-11), which focuses on “Task-oriented Conversational Modeling with Subjective Knowledge”. We focus on response generation and leverage a ranking strategy to ensemble individual models of BART, Long-T5, and a fine-tuned large language model based on LLaMA. The strategy is supplemented by other techniques like low rank adaptation to maintain efficient utilization of these large models while still achieving optimal performance. The experiments show that the ensemble method outperforms individual models and the baseline method. Our model was ranked 1st place in ROUGE_1, 2nd place in ROUGE_L score and 4th place in human evaluation among a total of 14 participating teams.
A prognostic model of cloud cover based on Satellite Data

Large uncertainties still remain about the mechanisms of genesis and interaction of clouds in a large scale environment. Through a semi‐empirical dynamical model using hourly data from TOGA‐COARE IOP (130E–180E and 15S–15N, 01.11.91–28.02.92), we show that the convective activity leading to clouds is a self‐regulating, threshold process embedded in a large‐scale environment. The convective activity is prescribed through a of hourly fractional cloud cover while the environmental forcings are defined in terms large‐scale moist state defined in terms of the average brightness temperature. A prognostic model is then developed for cloud cover as the dynamical variable. To validate the model we integrate it with a given initial condition from observed data. The model reproduces the observed spatio‐temporal structure of the cloud with a remarkable degree of success. We identify and quantify two thresholds for large‐scale forcing for genesis and intensity of high clouds.
Comparative genomics reveals the diversity of CRISPR-Cas systems among neonatal sepsis causing group B Streptococcus agalactiae

The pathogen Streptococcus agalactiae, or Group B Streptococcus (GBS) infection is the leading cause of neonatal sepsis and meningitis in neonates. In this study, we aimed to investigate the occurrence and diversity of the CRISPR-Cas system in S. agalactiae genomes using computational biology approaches. A total of 51 out of 52 complete genomes (98.07%) of S. agalactiae possess CRISPR arrays (75 CRISPR arrays) with 17 strains possessing multiple CRISPR arrays. There were only two CRISPR-Cas systems – type II-A system and type I-C system in S. agalactiae strains. RNA secondary structure analysis through direct repeat analysis showed that the analyzed strains could form stable secondary structures. The 16S rRNA phylogeny exhibited clustering of the strains into three major clades grouped on the type of CRISPR-Cas system. The anti-CRISPRs that contribute to CRISPR-Cas system diversity and prevent genome editing were also detected. These results provide valuable insights into elucidating the evolution, diversity, and function of CRISPR/Cas elements in this pathogen.
Pre-piRNA trimming safeguards piRNAs against erroneous targeting by RNA-dependent RNA Polymerase

In animal germ lines, The Piwi/piRNA pathway plays a crucial role in safeguarding genome integrity and promoting fertility. Following transcription from discrete genomic loci, piRNA precursors undergo nucleolytic processing at both 5’ and 3’ ends. The ribonuclease PARN-1 and its orthologs mediate piRNA 3’ trimming in worms, insects and mammals. Yet, the significance of this evolutionarily conserved processing step is not well understood. Employing C. elegans as a model organism, our recent work has demonstrated that 3’ trimming protects piRNAs against non-templated nucleotide additions and degradation. In this study, we present an unexpected finding that C. elegans deficient for PARN-1 accumulate a heretofore uncharacterized RNA species termed anti-piRNAs, which are antisense to piRNAs. These anti-piRNAs associate with Piwi proteins and display the propensity for a length of 17-19 nucleotides and 5’ guanine and adenine residues. We show that untrimmed pre-piRNAs in parn-1 mutants are modified by the terminal nucleotidyltransferase RDE-3 and erroneously targeted by the RNA-dependent RNA polymerase EGO-1, thereby giving rise to anti-piRNAs. Taken together, our work identifies a previously unknown class of small RNAs upon loss of parn-1 and provides mechanistic insight to activities of RDE-3, EGO-1 and Piwi proteins.
Frass fertilizers from mass-reared insects: species variation, heat treatment effects, and implications for soil application

Insect farming has gained popularity as a resource-efficient and eco-friendly method of managing organic wastes by converting them into high-quality protein, fat, and frass. Insect frass is a powerful organic fertilizer, enriching the soil with essential plant nutrients and enhancing plant defense mechanisms through chitin stimulation. Given the importance of frass commercialization for many insect farmers and the use of increasingly diverse organic wastes as insect feedstock, the need for legal guidelines to enable clean production practices has emerged. The recent introduction of a legal definition for frass and heat treatment requirements by the EU commission marks a significant step towards standardizing its quality. However, frass composition is influenced by numerous factors, and little is known about the processes shaping its nutritional profiles and contributing to its maturation. Here, we analyzed the physicochemical, plant-nutritional, and microbiological properties of black soldier fly, yellow mealworm, and Jamaican field cricket frass from mass-rearing operations and assessed the impact of hygienizing heat treatment. Frass properties varied significantly across insect species, revealing concentrations of plant available nutrients reaching as high as 7000 µg NH4+, 150 µg NO2-NO3--N, and 20 mg P per g of total solids. Heat treatment affected microbial activity by reducing basal respiration and microbial biomass carbon, but also reducing viable counts of pathogenic E. coli and Salmonella sp. In terms of microbiome composition, alpha diversity showed no significant differences between fresh and heat-treated frass samples within each insect species, but significant distinctions were observed across the three insect species. The soil application of frass reactivated and boosted soil microbial activity, suggesting no long-term detrimental effects on microorganisms. These results further highlight the potential of insect frass as nutrient rich organic fertilizer, with promising benefits for soil health and nutrient cycling. Graphical abstract: Physicochemical and microbiological assessment of frass from black soldier fly (BSF), yellow mealworm (YMW), and Jamaican field cricket (JFC) and the impact of heat treatment. TS = total solids, VS = volatile solids, TDS = total dissolved solids, BR = basal respiration, Cmic = microbial biomass carbon, MQ = metabolic quotient. n.s. : p > 0.05, *: p <= 0.05, **: p <= 0.01, ***: p <= 0.001, ****: p <= 0.0001, o.o. R. = out of range, b.d. l. = below detection limit.
A method to account for surface albedo heterogeneity in single‐column radiative transfer calculations under overcast conditions

[1] A simple parameterization to derive the broadband effective albedo over highly reflecting surfaces under overcast conditions is presented. High spatial variability in the surface albedo affects the downwelling solar irradiance in neighboring regions via the multiple reflections of light between the surface and the cloud base. The effective albedo is defined as the albedo of a homogeneous surface that would result in the same downwelling irradiance as observed at the observation point in the presence of a heterogeneous surface. The proposed method parameterizes the effective albedo using the cloud base height and a surface albedo map as inputs. The parameterization is based on the spatial distribution of surface reflections contributing to the downwelling irradiance at the observation site, which is approximated with a gamma distribution. The parameterization was validated against reference values of effective albedo derived from three-dimensional backward Monte Carlo and one-dimensional DISORT radiative transfer calculations for four idealized surface albedo maps and various specifications of cloud properties. It gave values of effective albedo very close to the reference calculations, performing substantially better than any other approach tested, also when applied to the retrieval of cloud optical depth. The method can be implemented into one-dimensional radiative transfer models or used to interpret broadband irradiance measurements in Polar coastal regions, in the marginal sea ice zones, or in patchy terrain with forests and snow-covered fields.