Miracle-dz/UniFAR-FTUs huggingface dataset:
MaintainoMATE: A GitHub App for Intelligent Automation of Maintenance Activities

Software development projects rely on issue tracking systems at the core of tracking maintenance tasks such as bug reports, and enhancement requests. Incoming issue-reports on these issue tracking systems must be managed in an effective manner. First, they must be labelled and then assigned to a particular developer with relevant expertise. This handling of issue-reports is critical and requires thorough scanning of the text entered in an issue-report making it a labor-intensive task. In this paper, we present a unified framework called MaintainoMATE, which is capable of automatically categorizing the issue-reports in their respective category and further assigning the issue-reports to a developer with relevant expertise. We use the Bidirectional Encoder Representations from Transformers (BERT), as an underlying model for MaintainoMATE to learn the contextual information for automatic issue-report labeling and assignment tasks. We deploy the framework used in this work as a GitHub application. We empirically evaluate our approach on GitHub issue-reports to show its capability of assigning labels to the issue-reports. We were able to achieve an F1-score close to 80\%, which is comparable to existing state-of-the-art results. Similarly, our initial evaluations show that we can assign relevant developers to the issue-reports with an F1 score of 54\%, which is a significant improvement over existing approaches. Our initial findings suggest that MaintainoMATE has the potential of improving software quality and reducing maintenance costs by accurately automating activities involved in the maintenance processes. Our future work would be directed towards improving the issue-assignment module.
The interplay between social and food environments on UK adolescents’ food choices: implications for policy

Abstract Factors from social and food environments can influence the food choices of adolescents in ways not experienced during childhood. Evidence suggests these two environments influence adolescents’ food choices independently, but there is limited knowledge of how the interplay between these environments influence adolescents’ diets. An enhanced understanding of this interplay surrounding adolescent food choice could aid the development of more nuanced interventions and policies. This qualitative study involved 13 online focus groups with adolescents (n = 45) aged 11–18 years, attending secondary school or college in England, UK. Data were analysed using thematic analysis. Social experiences which accompanied eating were perceived as more important than the food itself, and fast-food outlets were described as uniquely suited to facilitating these interactions. Young people wanted to spend their money on foods they considered worthwhile, but this did not always relate to the most affordable foods. Adolescents wanted to put little effort into making food decisions and appreciated factors that helped them make quick decisions such as prominent placement and eye-catching promotions on foods they wanted to buy. Chain food outlets were valued as they offered familiar and frequently advertised foods, which minimized the effort needed for food decisions. Adolescents’ sense of autonomy underpinned all themes. Participants described having limited opportunities to make their own food choices and they did not want to waste these buying unappealing ‘healthy’ foods. Interventions and government policies should align with adolescents’ experiences and values relating to food choice to ensure that they are effective with this important age group.
Statistical process control (SPC) for short production run with Cauchy distribution, a case study with corrected numbers approach

Abstract Controlling damages in a short production run is very subtle. Because the samples for each part are small, the control charts for each part can be obscure therefore the deviation of the actual from the nominal size of each part in a unique control chart will be applied. Differences between the control limits of various deviations can generate a heavy-tailed distribution. We will discuss it with an example of Cauchy distribution as a member of this family. From Phase (I) we will propose the Corrected Numbers and these numbers will be applied in Phase (II).
Personalization: Definition, Status, and Challenges Ahead

As is often the case with a good marketing buzzword, the term personalization is used rather loosely today. It has come to stand for an ultimate goal of customer relationship management by businesses. It has also come to mean delivery of information of high relevance to an individual. In any case, given the huge and rapidly growing amounts of computerized information, and the unprecedented level of competition for customers, personalization is one of the most important trends in data processing and businesses. This article aims to offer a reasonably encompassing definition of personalization, examine techniques in use today to support personalization, and provide directions for future research and development for realizing the full potential of personalization.
Gastrodin improves nerve cell injury and behaviors of depressed mice through Caspase‐3‐mediated apoptosis

Abstract Aim We investigated the effects and target of gastrodin (GAS) for treating depression through network pharmacology combined with experimentation. Methods The therapeutic target and signal of GAS for depression were analyzed by network pharmacology. Depression in mice was mimicked with a chronic unpredictable mouse stress (CUMS) model. Through open field, elevated plus maze, forced swimming, and tail suspension tests, the effects of GAS on the CUMS mice behaviors were examined, and the levels of neurotransmitters were detected. The histopathological changes were assayed by H&E and IHC staining, and the protein expressions were detected by Western blotting. Small molecule‐protein docking and molecular dynamics experiments were conducted to simulate the binding mode between GAS and Caspase‐3. Results Network pharmacological analysis revealed that Caspase‐3 was the action target of GAS. GAS could improve depression‐like behaviors in CUMS mice, elevate their neurotransmitter levels, ameliorate their nerve cell injury, and inhibit their Caspase‐3 expression. After knocking out Caspase‐3, the effects of GAS were inhibited. Molecular dynamics simulation and small molecule‐protein docking found that GAS bound to Caspase‐3 at SER25, inhibiting the maturation and activation of Caspase‐3. Conclusion We find that GAS can act as a Caspase‐3 inhibitor, which improves depression‐like behaviors and nerve cell injury in CUMS mice by inhibiting Caspase‐3‐mediated apoptosis.
Domain-specific cognitive impairment reflects prefrontal dysfunction in aged common marmosets

Age-related cognitive impairment is not expressed uniformly across cognitive domains. Cognitive functions that rely on brain areas that undergo substantial neuroanatomical changes with age often show age-related impairment, while those that rely on brain areas with minimal age-related change typically do not. The common marmoset has grown in popularity as a model for neuroscience research, but robust cognitive phenotyping, particularly as a function of age and across multiple cognitive domains, is lacking. This presents a major limitation for the development and evaluation of the marmoset as a model of cognitive aging, and leaves open the question of whether they exhibit age-related cognitive impairment that is restricted to some cognitive domains, as in humans. In this study, we characterized stimulus-reward association learning and cognitive flexibility in young adults to geriatric marmosets using a Simple Discrimination and a Serial Reversal task, respectively. We found that aged marmosets show transient impairment in “learning-to-learn” but have conserved ability to form stimulus-reward associations. Furthermore, aged marmosets have impaired cognitive flexibility driven by susceptibility to proactive interference. Since these impairments are in domains critically dependent on the prefrontal cortex, our findings support prefrontal cortical dysfunction as a prominent feature of neurocognitive aging. This work positions the marmoset as a key model for understanding the neural underpinnings of cognitive aging. Significance Statement Aging is the greatest risk factor for neurodegenerative disease development, and understanding why is critical for the development of effective therapeutics. The common marmoset, a short-lived non-human primate with neuroanatomical similarity to humans, has gained traction for neuroscientific investigations. However, the lack of robust cognitive phenotyping, particularly as a function of age and across multiple cognitive domains limits their validity as a model for age-related cognitive impairment. We demonstrate that aging marmosets, like humans, have impairment that is specific to cognitive domains reliant on brain areas that undergo substantial neuroanatomical changes with age. This work validates the marmoset as a key model for understanding region-specific vulnerability to the aging process.
Travelling waves or sequentially activated discrete modules: mapping the granularity of cortical propagation

Numerous studies have identified travelling waves in the cortex and suggested they play important roles in brain processing. These waves are most often measured using macroscopic methods that are unable to assess the local spiking activity underlying wave dynamics. Here we investigated the possibility that waves may not be travelling at the single neuron scale. We first show that sequentially activating two discrete brain areas can appear as travelling waves in EEG simulations. We next reproduce these results using an analytical model of two sequentially activated regions. Using this model, we were able to generate wave-like activity with variable directions, velocities, and spatial patterns, and to map the discriminability limits between travelling waves and modular sequential activations. Finally, we investigated the link between field potentials and single neuron excitability using large-scale measurements from turtle cortex ex-vivo. We found that while field potentials exhibit wave-like dynamics, the underlying spiking activity was better described by consecutively activated spatially adjacent groups of neurons. Taken together, this study suggests caution when interpreting phase delay measurements as continuously propagating wavefronts in two different spatial scales. A careful distinction between modular and wave excitability profiles across scales will be critical for understanding the nature of cortical computations.
MAGinator enables strain-level quantification of de novo MAGs

Motivation Metagenomic sequencing has provided great advantages in the characterization of microbiomes, but currently available analysis tools lack the ability to combine strain-level taxonomic resolution and abundance estimation with functional profiling of assembled genomes. In order to define the microbiome and its associations with human health, improved tools are needed to enable comprehensive understanding of the microbial composition and elucidation of the phylogenetic and functional relationships between the microbes. Results Here, we present MAGinator, a freely available tool, tailored for the profiling of shotgun metagenomics datasets. MAGinator provides de novo identification of subspecies-level microbes and accurate abundance estimates of metagenome-assembled genomes (MAGs). MAGinator utilises the information from both gene- and contig-based methods yielding insight into both taxonomic profiles and the origin of genes as well as genetic content, used for inference of functional content of each sample by host organism. Additionally, MAGinator facilitates the reconstruction of phylogenetic relationships between the MAGs, providing a framework to identify clade-level differences within subspecies MAGs. Availability and implementation MAGinator is available as a Python module at https://github.com/Russel88/MAGinator Contact Trine Zachariasen, trine_zachariasen@hotmail.com
Kinase inhibitor-induced cell-type specific vacuole formation in the absence of canonical ATG5-dependent autophagy

Pyridinyl imidazole class p38 MAPKα/β (MAPK14/MAPK11) inhibitors including SB202190 have been shown to induce a cell-type specific defective autophagy response resulting in micron-scale vacuole formation, autophagy-dependent death, and tumor growth suppression in vivo. We had earlier shown that this is an off-target effect of SB202190. Here we provide evidence that the cell-type specific vacuole formation is independent of canonical autophagy pathway. While SB202190 seems to interfere with autophagic flux in many cell lines in parallel to vacuolation, autophagy-deficient DU-145 cells and CRISPR/Cas9 gene-edited ATG5 knockout A549 cells also undergo vacuolation upon SB202190 treatment. Late-endosomal GTPase RAB7 colocalizes with these compartments and RAB7 GTP-binding seems to be essential for SB202190-induced vacuolation. RAB7 is a driver of tumor progression and interfering with RAB7-positive endo/lysosomal compartments may enhance cytotoxicity. A screen for modulators of SB202190-induced vacuolation revealed molecules including multi-kinase inhibitor Sorafenib as inhibitor of vacuolation and sorafenib co-treatment enhanced the cytotoxicity of SB202190. Moreover VE-821, an ATR kinase inhibitor was found to phenocopy the cell-type specific vacuolation response of SB202190. To identify the factors determining the cell-type specificity of the vacuolation response induced by SB-compounds and VE-821, we compared the transcriptomics data from vacuole forming and non-vacuole forming cancer cell lines and identified a gene expression signature which may define sensitivity of cancer cells to these small-molecule kinase inhibitors. Further analyses using the small molecule tools and the gene signature discovered here, could reveal novel mechanisms regulating this interesting phenotype relevant to anti-cancer therapy.
Single-cell analysis of Rohon-Beard neurons implicates Fgf signaling in axon maintenance and cell survival

Peripheral sensory neurons are a critical part of the nervous system that transmit a multitude of sensory stimuli to the central nervous system. During larval and juvenile stages in zebrafish, this function is mediated by Rohon-Beard somatosensory neurons (RBs). RBs are optically accessible and amenable to experimental manipulation, making them a powerful system for mechanistic investigation of sensory neurons. Previous studies provided evidence that RBs fall into multiple subclasses; however, the number and molecular make up of these potential RB subtypes have not been well defined. Using a single-cell RNA sequencing (scRNA-seq) approach, we demonstrate that larval RBs in zebrafish fall into three, largely non-overlapping classes of neurons. We also show that RBs are molecularly distinct from trigeminal neurons in zebrafish. Cross-species transcriptional analysis indicates that one RB subclass is similar to a mammalian group of A-fiber sensory neurons. Another RB subclass is predicted to sense multiple modalities, including mechanical stimulation and chemical irritants. We leveraged our scRNA-seq data to determine that the fibroblast growth factor (Fgf) pathway is active in RBs. Pharmacological and genetic inhibition of this pathway led to defects in axon maintenance and RB cell death. Moreover, this can be phenocopied by treatment with dovitinib, an FDA-approved Fgf inhibitor with a common side effect of peripheral neuropathy. Importantly, dovitinib-mediated axon loss can be suppressed by loss of Sarm1, a positive regulator of neuronal cell death and axonal injury. This offers a molecular target for future clinical intervention to fight neurotoxic effects of this drug.
OpgH is an essential regulator of Caulobacter morphology

Bacterial growth and division rely on intricate regulation of morphogenetic complexes to remodel the cell envelope without compromising envelope integrity. Significant progress has been made in recent years towards understanding the regulation of cell wall metabolic enzymes. However, other cell envelope components play a role in morphogenesis as well. Components required to maintain osmotic homeostasis are among these understudied envelope-associated enzymes that may contribute to cell morphology. A primary factor required to protect envelope integrity in low osmolarity environments is OpgH, the synthase of osmoregulated periplasmic glucans (OPGs). Here, we demonstrate that OpgH is essential in the ⍺-proteobacterium Caulobacter crescentus. Unexpectedly, depletion of OpgH results in striking asymmetric bulging and cell lysis, accompanied by misregulation of cell wall insertion and mislocalization of morphogenetic complexes. The enzymatic activity of OpgH is required for normal cell morphology as production of an OpgH mutant that disrupts a conserved glycosyltransferase motif phenocopies the depletion. Our data establish a surprising function for an OpgH homolog in morphogenesis and reveal an essential role of OpgH in maintaining proper cell morphology during normal growth and division in Caulobacter. Significance Bacteria must synthesize and fortify the cell envelope in a tightly regulated manner to orchestrate growth and adaptation. Osmoregulated periplasmic glucans (OPGs) are important, but poorly understood, constituents of Gram-negative cell envelopes that contribute to envelope integrity and protect against osmotic stress. Here, we determined that the OPG synthase OpgH plays a surprising, essential role in morphogenesis in Caulobacter crescentus. Loss of OpgH causes asymmetric cell bulging and lysis via misregulation of the localization and activity of morphogenetic complexes. Because cell envelope integrity is critical for bacterial survival, understanding how OpgH activity contributes to morphogenesis could aid in the development of antibiotic therapies.
Chloride intracellular channel (CLIC) proteins function as fusogens

Chloride Intracellular Channel (CLIC) family members uniquely transition between soluble and membrane-associated conformations. Despite decades of extensive functional and structural studies, CLICs’ function as ion channels remains debated, rendering our understanding of their physiological role incomplete. Here, we expose a novel function of CLIC5 as a fusogen. We demonstrate that purified CLIC5 directly interacts with the membrane and induces fusion, as reflected by increased liposomal diameter and lipid and content mixing between liposomes. Moreover, we show that this activity is facilitated by acidic pH, a known trigger for CLICs’ transition to a membrane-associated conformation, and that increased exposure of the hydrophobic inter-domain interface is crucial for this process. Finally, mutation of a conserved hydrophobic interfacial residue diminishes the fusogenic activity of CLIC5 in vitro and impairs excretory canal extension in C. elegans in vivo. Together, our results unravel the long-sought physiological role of these enigmatic proteins.
Sensitization with an allogeneic MHC class I molecule induces anti-tumor immunity in the absence of PD-1 in mice

To investigate the effect of a major histocompatibility complex class I (MHC-I) overexpression to augment immune sensitivity against tumors, we have generated the murine colorectal carcinoma cell line MC38 (with the endogenous H-2b haplotype) overexpressing the allogeneic mouse MHC-I cell surface molecule H-2Kd (MC38 H-2Kd). The tumorigenicity of unmodified parental cells (MC38 PT) and MC38 H-2Kd was tested in vivo by subcutaneous injection into the flank of wild-type (WT) and programmed death-1 (PD-1) knockout (KO) mice in a C57BL/6 (H-2b) genetic background. MC38 PT cells readily formed tumors and grew progressively in both WT and PD-1 KO mice. The speed of MC38 PT tumor growth was slower in PD-1 KO mice than in WT mice. In contrast, MC38 H-2Kd cells showed full sensitivity to rejection by the immune system in both naïve WT and PD-1 KO mice, indicated by spontaneous tumor regression. Next, we sought to determine the extent to which H-2Kd-overexpressing tumors could protect the mice against unmodified cancers. PD-1 KO mice were first sensitized with highly immunogenic MC38 H-2Kd cells and then challenged with weakly immunogenic MC38 PT cells. Intriguingly, all PD-1 KO mice gained immunity against the aggressive MC38 tumor and became tumor-free. Sensitizing PD-1 KO mice with growth-arrested (by the pre-treatment with mitomycin C, MMC) and the debris of MC38 H-2Kd tumors also provided full protection against the growth of secondary MC38 PT tumors. Most notably, sensitization with the debris of MC38 H-2Kd cells provided the long-term immunological memory against MC38 PT carcinoma cells. This finding implies that MC38 H-2Kd cells retain highly efficient and durable immunogenicity.
Adherence among orthodontic patients

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Immunohistochemical expression of matrix metalloproteinase-2 ( MMP-2 ) in common melanocytic nevi , dysplastic nevi and primary cutaneous malignant melanomas

MMPs play a significant role in the progression of different types of human tumors as well as malignant melanomas. MMP-2, which is also known as 72-kD type IV collagenase is a member of MMPs. The aim of this immunohistochemical study is to evaluate the role of MMP-2 expression in common melanocytic nevi, dysplastic nevi and primary cutaneous malignant melanomas. Formalin-fixed paraffin-embedded materials from 21 common melanocytic nevi (CMN), 42 dysplastic nevi (DN) and 18 primary cutaneous malignant melanomas (MM) were examined. Standard streptavidin-biotin immunoperoxidase method was used for immunostaining with MMP2 antibody. Both tumoral and stromal cytoplasmic MMP2 expressions in melanocytic lesions were scored semiquantitatively. MMP-2 immunoreactivity was not observed in stromal and/or melanocytic cells in either common melanocytic or dysplastic nevi. Eleven of 18 malignant melanomas expressed MMP-2. Five cases showed positive cytoplasmic staining only in stromal cells, and six cases in both stromal and melanocytic cells. MMP-2 was more commonly expressed at the tumor-stroma interface where significant amount of plasma cells and lymphocytes were observed. MMP-2 expression does not appear to be related to the pathobiology of benign melanocytic lesions such as common melanocytic nevi and dysplastic nevi. On the other hand, MMP-2 expression by the cells in the tumor stroma, particularly by endothelial cells and fibroblasts, may play a significant role in melanoma pathobiology.