Miracle-dz/UniFAR-FTUs huggingface dataset:
I Told You Tomorrow: Practical Time-Locked Secrets using Smart Contracts

A Time-Lock enables the release of a secret at a future point in time. Many approaches implement Time-Locks as cryptographic puzzles, binding the recovery of the secret to the solution of the puzzle. Since the time required to find the puzzle’s solution may vary due to a multitude of factors, including the computational effort spent, these solutions may not suit all scenarios. To overcome this limitation, we propose I Told You Tomorrow (ITYT), a novel way of implementing time-locked secrets based on smart contracts. ITYT relies on the blockchain to measure the elapse of time, and it combines threshold cryptography with economic incentives and penalties to replace cryptographic puzzles. We implement a prototype of ITYT on top of the Ethereum blockchain. The prototype leverages secure Multi-Party Computation to avoid any single point of trust. We also analyze resiliency to attacks with the help of economic game theory, in the context of rational adversaries. The experiments demonstrate the low cost and limited resource consumption associated with our approach.
An exploration into the relationship Irish cancer survivors’ have with nutrition post cancer treatment: a qualitative study

In Ireland, the number of individuals living with and beyond cancer equates to almost 4% of the population, with this number pro-jected to increase (1) . Little is currently known about how cancer changes perceptions and views on food and nutrition among cancer survivors. Such data gathered from a patient-centered perspective is instrumental for the development of future health interventions in this cohort. The aim of this study was to explore these perceptions and views amongst Irish cancer survivors ’ . Participants who were living on the Island of Ireland and had completed active cancer treatment at least six months ago were eli-gible for this study. Semi-structured focus groups were conducted online via Microsoft Teams in February 2021. The focus groups were audio-recorded and transcribed verbatim. This qualitative data was analysed using Braun and Clarke ’ s updated six-phase pro-cess for conducting re ﬂ exive thematic analysis (2) . Microsoft excel was used to manage the data as the sample size wasn ’ t large enough to require specialised qualitative software. After familiarisation with the data all transcripts were coded using an agreed data coding list. The coded transcripts were analysed for initial themes, which were further reviewed and developed. Finally, themes were re ﬁ ned, de ﬁ ned and named at meetings between the study team (NOC., L.K., and P.D.) until the emergent three themes were agreed upon. In total, ﬁ ve focus groups were held with 18 cancer survivors. The cohort was predominately female (n = 16) with a mean age of 51.1±12.5 years. Three core themes emerged (i) the role of nutrition (ii) cancer as a catalyst for change and (iii) the overall lack of nutritional support in oncology. The emergent themes highlighted how nutrition is perceived to have a variety
Lithium ion conductivity in Li2S–P2S5 glasses – building units and local structure evolution during the crystallization of superionic conductors Li3PS4, Li7P3S11 and Li4P2S7

Motivated by the high lithium ion conductivities of lithium thiophosphate glasses, a detailed study is performed on the local chemical nature of the thiophosphate building units within these materials. Using Raman and 31P MAS NMR (Magic Angle Spinning – Nuclear Magnetic Resonance) spectroscopy, the continuous change from dominant P2S74− (di-tetrahedral) anions to PS43− (mono-tetrahedral) anions with increasing Li2S fraction in the (Li2S)x(P2S5)(100−x) glasses is observed. In addition, synchrotron pair distribution function analysis (PDF) of synchrotron X-ray total scattering data is employed to monitor in situ crystallization and phase evolution in this class of materials. Depending on the composition, different crystalline phases evolve, which possess different decomposition temperatures into less conducting phases. The results highlight the critical influence of the local anionic building units on the cation mobility and thermal stability, with PS43− tetrahedra forming the most thermally robust glass ceramics with the highest ionic conductivity.
Characterization of in vitro 3D cultures

Over the past decade, 3D culture models of human and animal cells have found their way into tissue differentiation, drug development, personalized medicine and tumour behaviour studies. Embryoid bodies (EBs) are in vitro 3D cultures established from murine pluripotential stem cells, whereas tumoroids are patient‐derived in vitro 3D cultures. This thesis aims to describe a new implication of an embryoid body model and to characterize the patient‐specific microenvironment of the parental tumour in relation to tumoroid growth rate. In this thesis, we described a high‐throughput monitoring method, where EBs are used as a dynamic angiogenesis model. In this model, digital image analysis (DIA) is implemented on immunohistochemistry (IHC) stained sections of the cultures over time. Furthermore, we have investigated the correlation between the genetic profile and inflammatory microenvironment of parental tumours on the in vitro growth rate of tumoroids. The EBs were cultured in spinner flasks. The samples were collected at days 4, 6, 9, 14, 18 and 21, dehydrated and embedded in paraffin. The histological sections were IHC stained for the endothelial marker CD31 and digitally scanned. The virtual whole‐image slides were digitally analysed by Visiopharm® software. Histological evaluation showed vascular‐like structures over time. The quantitative DIA was plausible to monitor significant increase in the total area of the EBs and an increase in endothelial differentiation. The tumoroids were established from 32 colorectal adenocarcinomas. The in vitro growth rate of the tumoroids was followed by automated microscopy over an 11‐day period. The parental tumours were analysed by next‐generation sequencing for KRAS, TP53, PIK3CA, SMAD4, MAP2K1, BRAF, FGFR3 and FBXW7 status. The tumoroids established from KRAS‐mutated parental tumours showed a significantly higher growth rate compared to their wild‐type counterparts. The density of CD3+ T lymphocytes and CD68+ macrophages was calculated in the centre of the tumours and at the invasive margin of the tumours. The high density of CD3+ cells and the low density of CD68+ cells showed a significant correlation with a higher growth rate of the tumoroids. In conclusion, a novel approach for histological monitoring of endothelial differentiation is presented in the stem cell‐derived EBs. Furthermore, the KRAS status and density of CD3+ T cells and macrophages in the parental tumour influence the growth rate of the tumoroids. Our results indicate that these parameters should be included when tumoroids are to be implemented in personalized medicine
MetaProFi: A protein-based Bloom filter for storing and querying sequence data for accurate identification of functionally relevant genetic variants

Technological advances of next-generation sequencing present new computational challenges to develop methods to store and query these data in time- and memory-efficient ways. We present MetaProFi (https://github.com/kalininalab/metaprofi), a Bloom filter-based tool that, in addition to supporting nucleotide sequences, can for the first time directly store and query amino acid sequences and translated nucleotide sequences, thus bringing sequence comparison to a more biologically relevant protein level. Owing to the properties of Bloom filters, it has a zero false-negative rate, allows for exact and inexact searches, and leverages disk storage and Zstandard compression to achieve high time and space efficiency. We demonstrate the utility of MetaProFi by indexing UniProtKB datasets at organism- and at sequence-level in addition to the indexing of Tara Oceans dataset and the 2585 human RNA-seq experiments, showing that MetaProFi consumes far less disk space than state-of-the-art-tools while also improving performance.
Genome sequencing of the vermicompost strain Stenotrophomonas maltophilia UENF-4GII and population structure analysis of the S. maltophilia Sm3 genogroup

The Stenotrophomonas maltophilia complex (Smc) is a cosmopolitan bacterial group that has been proposed an emergent multidrug-resistant pathogen. Taxonomic studies support the genomic heterogeneity of Smc, which comprises genogroups exhibiting a range of phenotypically distinct strains from different sources. Here, we report the genome sequencing and in-depth analysis of S. maltophilia UENF-4GII, isolated from vermicompost. This genome harbors a unique region encoding a penicillin-binding protein (pbpX) that was carried by a transposon, as well as horizontally-transferred genomic islands involved in anti-phage defense via DNA modification, and pili glycosylation. We also analyzed all available Smc genomes to investigate genes associated with resistance and virulence, niche occupation, and population structure. S. maltophilia UENF-4GII belongs to genogroup 3 (Sm3), which comprises three phylogenetic clusters (PC). Pan-GWAS analysis uncovered 471 environment-associated and 791 PC-associated genes, including antimicrobial resistance (e.g. blaL1 and blaR1) and virulence determinants (e.g. treS and katG) that provide insights on the resistance and virulence potential of Sm3 strains. Together, the results presented here provide the grounds for more detailed clinical and ecological investigations of S. maltophilia.
A practical framework RNMF for the potential mechanism of cancer progression with the analysis of genes cumulative contribution abundance

Mutational signatures can reveal the mechanism of tumorigenesis. We developed the RNMF software for mutational signatures analysis, including a key model of cumulative contribution abundance (CCA) which was designed to highlight the association between genes and mutational signatures. Applied it to 1073 esophageal squamous cell carcinoma (ESCC) and found that APOBEC signatures (SBS2* and SBS13*) mediated the occurrence of PIK3CA E545k mutation. Furthermore, we found that age signature is strongly linked to the TP53 R342* mutation. In addition, the CCA matrix image data of genes in the signatures New, SBS3* and SBS17b* were helpful for the preliminary evaluation of shortened survival outcome. In a word, RNMF can successfully achieve the correlation analysis of genes and mutational signatures, proving a strong theoretical basis for the study of tumor occurrence and development mechanism and clinical adjuvant medicine.
Phase transition specified by a binary code patterns the vertebrate eye cup

The developing vertebrate eye cup is partitioned into the neural retina (NR), the retinal pigmented epithelium (RPE) and the ciliary margin (CM). By single cell analysis, we showed that a gradient of FGF signaling regulates demarcation and subdivision of the CM and controls its stem cell-like property of self-renewal, differentiation and survival. This regulation by FGF is balanced by an evolutionarily conserved Wnt signaling gradient induced by the lens ectoderm and the periocular mesenchyme, which specifies the CM and the distal RPE. These two morphogen gradients converge in the CM where FGF signaling promotes Wnt signaling by stabilizing β-catenin in a GSK3β-independent manner. We further showed that activation of Wnt signaling converts the NR to either the CM or the RPE depending on the level of FGF signaling. Conversely, activation of FGF transforms the RPE to the NR or CM dependent on Wnt activity. We demonstrated that the default fate of the eye cup is the NR, but synergistic FGF and Wnt signaling promotes CM formation both in vivo and in retinal organoid culture of human iPS cells. Our study reveals that the vertebrate eye develops through phase transition determined by a combinatorial code of FGF and Wnt signaling.
Response of Posidonia oceanica (L.) Delile and its associated N2 fixers to different combinations of temperature and light levels

Ocean warming and water turbidity are threats for the persistence of seagrass meadows and their effects on the productivity of seagrasses and the functioning of their associated microorganisms have not been studied extensively. The purpose of this study was to assess the effects of different light levels and temperatures on Posidonia oceanica, the endemic seagrass species in the Mediterranean Sea, and their N2 fixing community, which contributes importantly to the nitrogen requirements and high productivity of the plants. Aquarium experiments were conducted in winter when the plants are more vulnerable to changes in temperature, subjecting them to short-term exposures to ambient (15.5 °C) and elevated temperatures (ambient+5.5 °C) and at limited (13 μmol photons m-2 s-1) and saturating light conditions (124 μmol photons m-2 s-1). Primary production, chlorophyll content, reactive oxygen species production, polyphenols content, the nifH gene expression, N2 fixation and alkaline phosphatase activities were measured in different plant tissues. Plants incubated at ambient temperature and high light exhibited enhanced total chlorophyll production and significantly higher gross and net primary production, which were approximately two-fold compared to the rest of the treatments. The oxidative stress analyses revealed increased production of reactive oxygen species in young leaves incubated at ambient temperature and saturating light, while the polyphenols content in top leaves was considerably higher under elevated temperatures. In contrast, N2 fixation and alkaline phosphatase rates were significantly higher under elevated temperature and low light levels. The presence of the N2 fixing phylotypes UCYN-A, -B and -C was detected through genetic analyses, with UCYN-B demonstrating the highest nifH gene transcription levels at elevated temperatures. These findings emphasize the significant role of irradiance on the productivity of P. oceanica and the temperature dependence of the N2 fixation process in winter.
Crystalline deposits reveal caste identity of late embryos and larvae of the ant Cardiocondyla obscurior

Social insects are interesting models for the study of anticipatory developmental plasticity because of the striking differentiation into reproductive queens and functionally sterile workers. A few ant genera, including Cardiocondyla, represent the pinnacle of social evolution in the Hymenoptera, where workers have completely lost their reproductive organs, minimizing reproductive conflicts between queens and workers. Here we show that late embryos and larvae of queens of the ant C. obscurior can be identified by the appearance of urate deposits around the forming ovaries. The discovery of caste-specific urate patterns in C. obscurior and three additional Cardiocondyla species will facilitate future studies of developmental plasticity in ants.
Redox Kinetics of Nonstoichiometric Oxides

Cerium oxide (CeO2-δ) and its derivatives are the most attractive materials under consideration for solar-driven thermochemical production of chemical fuels. Understanding the rate-limiting factors in fuel production is essential for maximizing the efficacy of the thermochemical process. The rate of response of the porous ceria structured with architectural features typical of those employed in solar reactors was measured via electrical conductance relaxation methods. A transition from behavior controlled by material surface reaction kinetics to that controlled by sweep-gas supply rates is observed on increasing temperature, increasing volume specific surface area, and decreasing normalized gas flow rate. The transition behavior is relevant not only for optimal reactor operation and architectural design of material, but also for accurate measurement of material properties. The redox kinetics of undoped ceria, CeO2-δ at extreme high temperature (1400 °C) was investigated using the electrical conductivity relaxation method, and those of 10% Pr doped ceria at low temperature (700 °C) were done using the mass relaxation method. It was demonstrated under sufficiently high gas flow rates relative to the mass of the oxide, which is required in order to overcome gas phase limitations and access the material kinetic properties. Furthermore, the surface reaction rate constant of undoped ceria, ,kChem, was investigated at high temperature (1400 °C) in humidified gas atmosphere, in consideration of the operating conditions in thermochemical fuel production system. It was demonstrated that H2O potentially plays a role of oxidants as increasing temperature and/or decreasing oxygen partial pressure; thus in such thermodynamic conditions, pH2O, besides temperature and pO2, needs to be carefully considered in surface reaction study. In addition to relaxation experiments under small driving force for redox reaction, the kinetics of surface related oxidation reaction under large chemical driving force (large ΔpO2 change) was investigated by mass relaxation method. Based on the normalized reaction rates of several possible rate determining steps, the relaxation behavior in oxygen concentration for all possible rate determining steps was computed. On the comparison with the experimental results, the most probable rate determining step was suggested (reduction of diatomic oxygen from neutral oxygen molecule to superoxide), and the oxidation kinetics under large driving force was explained.
Probing 3’UTRs as modular regulators of gene expression

Genes are commonly abstracted into a coding sequence and cis-regulatory elements (CREs), such as promoter and terminator regions, and short sequence motifs within these regions. Modern cloning techniques allow easy assembly of synthetic genetic constructs from discrete cis-regulatory modules. However, it is unclear how much the contributions of CREs to gene expression depend on other CREs in the host gene. Using budding yeast, we probe the extent of composability, or independent effects, of distinct CREs. We confirm that the quantitative effect of a terminator on gene expression depends on both promoter and coding sequence. We then explore whether individual cis-regulatory motifs within terminator regions display similar context dependence, focusing on putative regulatory motifs inferred using transcriptome-wide datasets of mRNA decay. We construct a library of diverse reporter genes, consisting of different combinations of motifs within various terminator contexts, paired with different promoters, to test the extent of composability. Our results show that the effect of a motif on RNA abundance depends both on its host terminator, and also on the associated promoter sequence. Consequently, this emphasises the need for improved motif inference algorithms that include both local and global context effects, which in turn could aid researchers in the accurate use of diverse CREs for the engineering of synthetic genetic constructs.
Filter Media Comparison for the Removal of Brettanomyces bruxellensis from Wine

Brettanomyces bruxellensis is a wine-spoilage yeast of significant concern to wine producers, and its removal by filtration is not fully understood. The aim of this work was to compare the efficacy of filters, having different compositions and micron ratings, to remove B. bruxellensis from wine. Wines inoculated with a B. bruxellensis strain were used, and the U.S. Food and Drug Administration guidelines for filter validation for aseptic processing were followed. Polypropylene filters of 0.6 and 1.0 µm ratings yielded wines with high Brettanomyces cell counts. No cells were detected in wines filtered through polyethersulfone filters of 0.45, 0.65, and 1.0 µm, or through X grade glass microfiber filter. This work showed that different filter compositions with similar micron ratings result in variable retention of B. bruxellensis, highlighting that filter media are relevant for removal mechanisms, and pointing to the importance of a complete characterization of filter media when addressing Brettanomyces removal from wine.
NLRP1B and NLRP3 control the host response following colonization with the commensal protist Tritrichomonas musculis

Commensal intestinal protozoa, unlike their pathogenic relatives, are neglected members of the mammalian microbiome. These microbes have a significant impact on the host’s intestinal immune homeostasis, typically by elevating anti-microbial host defense. Tritrichomonas musculis (T. mu), a protozoan gut commensal, strengthens the intestinal host defense against enteric Salmonella infections through Asc- and Il1r1-dependent Th1 and Th17 cell activation. However, the underlying inflammasomes mediating this effect remain unknown. Here, we report that colonization with T. mu results in an increase in luminal extracellular ATP, elevated levels of IL-1β, and increased numbers of IL-18 receptor-expressing Th1 and Th17 cells in the colon. Mice deficient in either Nlrp1b or Nlrp3 failed to display these protozoan-driven immune changes and lost resistance to enteric Salmonella infections even in the presence of T. mu. These findings demonstrate that T. mu-mediated host protection requires sensors of extra and intracellular ATP to confer resistance to enteric Salmonella infections. KEY POINTS Intestinal colonization with the commensal Tritrichomonas musculis elevates luminal ATP levels NLRP1B and NLRP3 activation is required for Tritrichomonas musculis-driven Th cell response.
Nrf2 is a central regulator of the metabolic landscape in macrophages and finetunes their inflammatory response

To overcome oxidative, inflammatory, and metabolic stress, cells have evolved networks of cytoprotective proteins controlled by nuclear factor erythroid 2 p45-related factor 2 (Nrf2) and its main negative regulator the Kelch-like ECH associated protein 1 (Keap1). Here, we used high-resolution mass-spectrometry to characterize the proteomes of macrophages with genetically altered Nrf2 status. Our analysis revealed significant differences among the genotypes in cellular metabolism and redox homeostasis, which we validated with respirometry and metabolomics, as well as in anti-viral immune pathways and the cell cycle. Nrf2 status significantly affected the proteome following lipopolysaccharide (LPS) stimulation, with alterations in redox, carbohydrate and lipid metabolism, and innate immunity observed. Of note, Nrf2 activation was found to promote mitochondrial fusion in inflammatory macrophages. The Keap1 inhibitor, 4-octyl itaconate (4-OI), a derivative of the mitochondrial immunometabolite itaconate, remodeled the inflammatory macrophage proteome, increasing redox and suppressing anti-viral immune effectors in a Nrf2-dependent manner. These data suggest that Nrf2 activation facilitates metabolic reprogramming and mitochondrial adaptation, and finetunes the innate immune response in macrophages. Graphical abstract Highlights First high-resolution proteome of macrophages with genetically altered Nrf2 status Nrf2 is key regulator of macrophage redox and intermediary metabolism Nrf2 finetunes the inflammatory response suppressing anti-viral immune and cytokine effectors, whilst promoting T cell activation factors Nrf2 regulates mitochondrial adaptation in inflammatory macrophages promoting the formation of a fused network 4-octyl itaconate (4-OI) suppresses anti-viral immune effectors in inflammatory macrophages in a Nrf2-dependent manner