Miracle-dz/UniFAR-FTUs huggingface dataset:
Linear Quadratic Regulator for Resource-Efficient Cloud Services

1 PROBLEM AND MOTIVATION The run-time performance of modern applications deployed within containers in the cloud critically depends on the amount of provisioned resources. Provisioning fewer resources can result in performance degradation and costly SLA violations; while allocating more resources leads to wasted money and poor resource utilization. Moreover, these applications undergo striking variations in load patterns. To automatically adapt resources in response to changes in load, an autoscaler applies predefined heuristics to add or remove resources allocated for an application based on usage thresholds. However, it is extremely challenging to configure thresholds and scaling parameters in an applicationagnostic manner without deep workload analysis. Poor resource efficiency results in high operating costs and energy expenditures for all cloud-based enterprises. To improve resource efficiency over safe and hand-tuned autoscaling schemes reinforcement learning (RL) based approaches [3, 4] learn an optimal scaling actions through experience (trial-anderror) for every application state, based on the input workload, or other variables. After the learning agent executes an action, it receives a response from the environment, based on the usefulness of the action. The agent is inclined to execute actions that provide higher rewards, thus reinforcing better actions. However, these proposed approaches suffer from the curse of dimensionality [2]. The state and action space to be discretized grows exponentially with the number of state variables, leading to scalability problems, manifested in unacceptable execution times in updation and selection of the next action to be executed in online setting. Moreover, these methods require huge amount of of samples to learn and thus often lack stability and interpretability of policy.
The evolution of the concept of synesthesia in the nineteenth century as revealed through the history of its name

ABSTRACT Synesthesia is a rare perceptual condition causing unusual sensations, which are triggered by the stimulation of otherwise unrelated modalities (e.g., the sensation of colors triggered when listening to music). In addition to the name it takes today, the condition has had a wide variety of designations throughout its scientific history. These different names have also been accompanied by shifting boundaries in its definition, and the literature has undergone a considerable process of change in the development of a term for synesthesia, starting with “obscure feeling” in 1772, and ending with the first emergence of the true term “synesthesia” or “synæsthesiæ” in 1892. In this article, we will unpack the complex history of this nomenclature; provide key excerpts from central texts, in often hard-to-locate sources; and translate these early passages and terminologies into English.
Proceedings of the 9th European Lisp Symposium (ELS 2016), Kraków, Poland, May 9-10, 2016

Typically, beginner programmers do not master the style rules of the programming language they are using and, frequently, do not have yet the logical agility to avoid writing redundant code. As a result, although their programs might be correct, they can also be improved and it is important for the programmer to learn about the improvements that, without changing the meaning of the program, simplify it or transform it to follow the style rules of the language. These kinds of transformations are the realm of refactoring tools. However, these tools are typically associated with sophisticated integrated development environments (IDEs) that are excessively complex for beginners. In this paper, we present a refactoring tool designed for beginner programmers, which we made available in DrRacket, a simple and pedagogical IDE. Our tool provides several refactoring operations for the typical mistakes made by beginners and is intended to be used as part of their learning process.
Lipidomics Detection of Brain Cardiolipins in Plasma Is Associated With Outcome After Cardiac Arrest

Objectives: Brain mitochondrial dysfunction limits neurologic recovery after cardiac arrest. Brain polyunsaturated cardiolipins, mitochondria-unique and functionally essential phospholipids, have unprecedented diversification. Since brain cardiolipins are not present in plasma normally, we hypothesized their appearance would correlate with brain injury severity early after cardiac arrest and return of spontaneous circulation. Design: Observational case-control study. Setting: Two medical centers within one city. Participants (Subjects): We enrolled 41 adult cardiac arrest patients in whom blood could be obtained within 6 hours of resuscitation. Two subjects were excluded following outlier analysis. Ten healthy subjects were controls. Sprague-Dawley rats were used in asphyxial cardiac arrest studies. Interventions: None. Measurements and Main Results: We developed a high-resolution liquid chromatography/mass spectrometry method and determined cardiolipins speciation in human brain, heart, and plasma within 6 hours of (return of spontaneous circulation) from 39 patients with cardiac arrest, 5 with myocardial infarction, and 10 healthy controls. Cerebral score was derived from brain-specific cardiolipins identified in plasma of patients with varying neurologic injury and outcome. Using a rat model of cardiac arrest, cardiolipins were quantified in plasma, brain, and heart. Human brain exhibited a highly diverse cardiolipinome compared with heart that allowed the identification of brain-specific cardiolipins. Nine of 26 brain-specific cardiolipins were detected in plasma and correlated with brain injury. The cerebral score correlated with early neurologic injury and predicted discharge neurologic/functional outcome. Cardiolipin (70:5) emerged as a potential point-of-care marker predicting injury severity and outcome. In rat cardiac arrest, a significant reduction in hippocampal cardiolipins corresponded to their release from the brain into systemic circulation. Cerebral score was significantly increased in 10 minutes versus 5 minutes no-flow cardiac arrest and naïve controls. Conclusions: Brain-specific cardiolipins accumulate in plasma early after return of spontaneous circulation and proportional to neurologic injury representing a promising novel biomarker.
teen Mental Health First Aid as a school-based intervention for improving peer support of adolescents at risk of suicide: Outcomes from a cluster randomised crossover trial

Objectives: The aims of this study were to assess evidence for a novel, universal mental health literacy programme in the school setting (teen Mental Health First Aid) as an intervention to improve peer support towards adolescents at risk of suicide and to examine whether participation in a school-based programme dealing with suicide was distressing to participants. Method: In a cluster randomised crossover trial, Australian high school students aged 15–17 years (N = 1605, 44.74% female, Mage = 15.87) received either teen Mental Health First Aid or a matched control physical first aid course. Data were collected before, immediately after and 12 months after training through online surveys assessing correct recognition of suicidality and intentions to help a fictional peer (John) who was depicted as experiencing depressive symptoms and suicidal thoughts in a vignette. Students were also asked whether any information in the training or surveys was found distressing and completed a validated measure of psychological distress (the Kessler Psychological Distress Scale). Results: Students receiving teen Mental Health First Aid training were much more likely to report an increase from pre- to post-training in recognition of suicidality (OR = 1.97, 95% CI = [1.14, 3.39], p = 0.02) and appropriate first aid intentions towards a peer at risk of suicide than students receiving physical first aid (OR = 35.40, 95% CI = [19.86, 63.14], p < 0.001). Twelve months after training, most effects were still significant. Although a greater proportion of teen Mental Health First Aid participants self-reported feeling briefly distressed after the training, there was no evidence of greater distress at 12 months on the Kessler Psychological Distress Scale. Conclusion: teen Mental Health First Aid is effective in increasing recognition of and intentions to assist a suicidal peer. Although the open discussion of mental health first aid for a suicidal peer was distressing for some students, results suggest this was transient and not associated with harm. Future studies are required to ascertain whether these increases are indeed associated with better provision of support and prevention of youth suicide.
Hidden resources in the Escherichia coli genome restore PLP synthesis and robust growth after deletion of the essential gene pdxB

Significance The evolution of new metabolic pathways has been a driver of diversification from the last universal common ancestor 3.8 billion y ago to the present. Bioinformatic evidence suggests that many pathways were assembled by recruiting promiscuous enzymes to serve new functions. However, the processes by which new pathways have emerged are lost in time. We have little information about the environmental conditions that fostered emergence of new pathways, the genome context in which new pathways emerged, and the types of mutations that elevated flux through inefficient new pathways. Experimental laboratory evolution has allowed us to evolve a new pathway and identify mechanisms by which mutations increase fitness when an inefficient new pathway becomes important for survival. PdxB (erythronate 4-phosphate dehydrogenase) is expected to be required for synthesis of the essential cofactor pyridoxal 5′-phosphate (PLP) in Escherichia coli. Surprisingly, incubation of the ∆pdxB strain in medium containing glucose as a sole carbon source for 10 d resulted in visible turbidity, suggesting that PLP is being produced by some alternative pathway. Continued evolution of parallel lineages for 110 to 150 generations produced several strains that grow robustly in glucose. We identified a 4-step bypass pathway patched together from promiscuous enzymes that restores PLP synthesis in strain JK1. None of the mutations in JK1 occurs in a gene encoding an enzyme in the new pathway. Two mutations indirectly enhance the ability of SerA (3-phosphoglycerate dehydrogenase) to perform a new function in the bypass pathway. Another disrupts a gene encoding a PLP phosphatase, thus preserving PLP levels. These results demonstrate that a functional pathway can be patched together from promiscuous enzymes in the proteome, even without mutations in the genes encoding those enzymes.
The multikinase inhibitor RXDX-105 is effective against neuroblastoma in vitro and in vivo

Neuroblastoma is the most common extracranial solid tumor of childhood and accounts for 15% of all pediatric cancer-related deaths. New therapies are needed to improve outcomes for children with high-risk and relapsed tumors. Inhibitors of the RET kinase and the RAS-MAPK pathway have previously been shown to be effective against neuroblastoma, suggesting that combined inhibition may have increased efficacy. RXDX-105 is a small molecule inhibitor of multiple kinases, including the RET and BRAF kinases. We found that treatment of neuroblastoma cells with RXDX-105 resulted in a significant decrease in cell viability and proliferation in vitro and in tumor growth and tumor vascularity in vivo. Treatment with RXDX-105 inhibited RET phosphorylation and phosphorylation of the MEK and ERK kinases in neuroblastoma cells and xenograft tumors, and RXDX-105 treatment induced both apoptosis and cell cycle arrest. RXDX-105 also showed enhanced efficacy in combination with 13-cis-retinoic acid, which is currently a component of maintenance therapy for children with high-risk neuroblastoma. Our results demonstrate that RXDX-105 shows promise as a novel therapeutic agent for children with high-risk and relapsed neuroblastoma.
Performance comparison of reverse transcriptases for single-cell studies

Background Recent technical advances allowing quantification of RNA from single cells are revolutionizing biology and medicine. Currently, almost all single-cell transcriptomic protocols rely on conversion of RNA to cDNA by reverse transcription (RT). However, RT is recognized as highly limiting step due to its inherent variability and suboptimal sensitivity, especially at minute amounts of RNA. Primary factor influencing RT outcome is reverse transcriptase (RTase). Recently, several new RTases with potential to decrease the loss of information during RT have been developed, but the thorough assessment of their performance is missing. Methods We have compared the performance of 11 RTases in RT-qPCR on single-cell and 100-cell bulk templates using two priming strategies: conventional mixture of random hexamers with oligo(dT)s and reduced concentration of oligo(dT)s mimicking common single-cell RNA-Seq library preparation protocols. Based on the performance, two RTases were further tested in high-throughput single-cell experiment. Results All RTases tested reverse transcribed low-concentration templates with high accuracy (R2 > 0.9445) but variable reproducibility (median CVRT = 40.1 %). The most pronounced differences were found in the ability to capture rare transcripts (0 - 90% reaction positivity rate) as well as in the rate of RNA conversion to cDNA (7.3 - 124.5 % absolute yield). Finally, RTase performance and reproducibility across all tested parameters were compared using Z-scores and validity of obtained results was confirmed in a single-cell model experiment. The better performing RTase provided higher positive reaction rate and expression levels and improved resolution in clustering analysis. Conclusions We performed a comprehensive comparison of 11 RTases in low RNA concentration range and identified two best-performing enzymes (Maxima H-; SuperScript IV). We found that using better-performing enzyme (Maxima H-) over commonly-used below-average performer (SuperScript II) increases the sensitivity of single-cell experiment. Our results provide a reference for the improvement of current single-cell quantification protocols.
Molecular and functional evidence of phosphatidylserine synthase in Vibrio parahaemolyticus

Phosphatidylserine synthase (Pss) catalyzes phosphatidylserine synthesis, which is critical to synthesizing the component of cell membrane. However, few putative pss genes of bacteria have been studied. In this study, it was found that Vibrio parahaemolyticus, a common foodborne pathogen that causes human gastroenteritis, has a type I Pss with two HKD motifs and is a phospholipase D superfamily member. The transcriptional start site of pss was mapped through sequencing and was identified at −37 nucleotides upstream of the start codon. Pss mRNA was found to be expressed mainly during the exponential phase. In addition, the promoter was identified using a lux reporter assay and gel shift assay with an RNA polymerase. To analyze the catalytic activity, a soluble form of His6‐tagged recombinant Pss was overexpressed and purified from Escherichia coli. Using matrix‐assisted laser desorption ionization‐time of flight mass spectrometry, it was found that Pss can catalyze cytidine diphosphate diacylglycerol and L‐serine to form phosphatidylserine. Since Pss is conserved in vibrios, the current study can promote understanding the biosynthesis of phospholipid in Vibrio bacteria that might cause vibriosis. This is the first report of molecular characterization of the pss gene and identification of Pss enzyme activity in V. parahaemolyticus using matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry.
Lactose and Fructo-oligosaccharides Increase Visceral Sensitivity in Mice via Glycation Processes, Increasing Mast Cell Density in Colonic Mucosa.

BACKGROUND AND AIMS Irritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and erratic bowel habits. A diet low in fermentable oligo-, di-, mono-saccharides and polyols (FODMAPs) can reduce symptoms of IBS, possibly by reducing microbial fermentation products. We investigated whether ingestion of FODMAPs can induce IBS-like visceral hypersensitivity mediated by fermentation products of intestinal microbes in mice. METHODS C57Bl/6 mice were gavaged with lactose, with or without the anti-glycation agent pyridoxamine, or saline (controls) daily for 3 weeks. A separate group of mice were fed a diet containing fructo-oligosaccharides, with or without pyridoxamine in drinking water, or a normal chow diet (controls) for 6 weeks. Feces were collected and analyzed by 16S rRNA gene sequencing and bacterial community analyses. Abdominal sensitivity was measured by electromyography and mechanical von Frey filament assays. Colon tissues were collected from some mice and analyzed by histology and immunofluorescence, to quantify mast cells and expression of advanced glycosylation end-product specific receptor (AGER). RESULTS Mice gavaged with lactose or fed fructo-oligosaccharides had increased abdominal sensitivity compared with controls, associated with increased numbers of mast cells in colon and expression of the receptor for AGER in proximal colon epithelium. These effects were prevented by administration of pyridoxamine. Lactose and/or pyridoxamine did not induce significant alterations in the composition of the fecal microbiota. Mass spectrometric analysis of carbonyl compounds in fecal samples identified signatures associated with mice given lactose or fructo-oligosaccharides vs controls. CONCLUSION We found that oral administration of lactose or fructo-oligosaccharides to mice increases abdominal sensitivity, associated with increased numbers of mast cells in colon and expression of AGER; these can be prevented with an anti-glycation agent. Lactose and/or pyridoxamine did not produce alterations in fecal microbiota of mice. Our findings indicate that preventing glycation reactions might reduce abdominal pain in patients with IBS with sensitivity to FODMAPs.
Chlamydia trachomatis: when the virulence-associated genome backbone imports a prevalence-associated major antigen signature

Chlamydia trachomatis is the most prevalent sexually transmitted bacterium worldwide and the causative agent of trachoma. Its strains are classified according to their ompA genotypes, which are strongly linked to differential tissue tropism and disease outcomes [ocular disease, urogenital disease and lymphogranuloma venereum (LGV)]. While the genome-based species phylogenetic tree presents four main clades correlating with tropism/prevalence, namely ocular, LGV, urogenital T1 (more prevalent genotypes) and urogenital T2 (less prevalent genotypes), inter-clade exchange of ompA is considered a rare phenomenon probably mediating marked tropism alterations. An LGV epidemic, associated with the clonal expansion of the L2b genotype, has emerged in the last few decades, raising concerns particularly due to its atypical clinical presentation (ulcerative proctitis) and circulation among men who have sex with men (MSM). Here, we report an LGV outbreak, mostly affecting human immunodeficiency virus-positive MSM engaging in high-risk sexual practices, caused by an L2b strain with a rather unique non-LGV ompA signature that precluded the laboratory notification of this outbreak as LGV. C. trachomatis whole-genome capture and sequencing directly from clinical samples was applied to deeply characterize the genomic backbone of this novel LGV outbreak-causing clone. It revealed a chimeric genome structure due to the genetic transfer of ompA and four neighbouring genes from a serovar D/Da strain, likely possessing the genomic backbone associated with the more prevalent urogenital genotypes (T1 clade), to an LGV (L2b) strain. The hybrid L2b/D-Da strain presents the adhesin and immunodominant antigen MOMP (major outer membrane protein) (encoded by ompA) with an epitope repertoire typical of non-invasive genital strains, while keeping the genome-dispersed virulence fingerprint of a classical LGV strain. As previously reported for inter-clade ompA exchange among non-LGV clades, this novel C. trachomatis genomic mosaic involving a contemporary epidemiologically and clinically relevant LGV strain may have implications on its transmission, tissue tropism and pathogenic capabilities. The emergence of variants with epidemic and pathogenic potential highlights the need for more focused surveillance strategies to capture C. trachomatis evolution in action.
Tumor‐associated macrophages secrete CC‐chemokine ligand 2 and induce tamoxifen resistance by activating PI3K/Akt/mTOR in breast cancer

Breast cancer is the most prevalent malignancy among women. Although endocrine therapy is effective, the development of endocrine resistance is a major clinical challenge. The tumor microenvironment (TME) promotes tumor malignancy, and tumor‐associated macrophages (TAM) within the TME play a crucial role in endocrine resistance. Herein, we aimed to elucidate the relationship between TAM and the endocrine‐resistant phenotype of breast cancer. Macrophages were cultured with conditioned medium (CM) from tamoxifen‐sensitive (MCF7‐S) or ‐resistant (MCF7‐R) MCF7 breast cancer cells. M2 polarization was detected by CD163 immunofluorescence. To determine the effect on endocrine resistance, MCF7 cells were cultured in the supernatant of different TAM, and then treated with tamoxifen. CC‐chemokine ligand 2 (CCL2) immunohistochemistry was carried out on pathological sections from 100 patients with invasive estrogen receptor‐positive breast cancer. We found that macrophages cultured in the CM of MCF7‐S and MCF7‐R cells were induced into TAM, with a more obvious M2 polarization in the latter. Tamoxifen resistance was increased by culture in TAM medium. TAM secreted CCL2, which increased endocrine resistance in breast cancer cells through activation of the PI3K/Akt/mTOR signaling pathway. High expression of CCL2 was correlated with infiltration of CD163+macrophages (r = 0.548, P < .001), and patients with high CCL2 expression presented shorter progression‐free survival than those with low CCL2 expression (P < .05). We conclude that CCL2 secreted by TAM activates PI3K/Akt/mTOR signaling and promotes an endocrine resistance feedback loop in the TME, suggesting that CCL2 and TAM may be novel therapeutic targets for patients with endocrine‐resistant breast cancer.
Social behaviour as an emergent property of embodied curiosity: a robotics perspective

Social interaction is an extremely complex yet vital component in daily life. We present a bottom-up approach for the emergence of social behaviours from the interaction of the curiosity drive, i.e. the intrinsic motivation to learn as much as possible, and the embedding environment of an agent. Implementing artificial curiosity algorithms in robots that explore human-like environments results in the emergence of a hierarchical structure of learning and behaviour. This structure resembles the sequential emergence of behavioural patterns in human babies, culminating in social behaviours, such as face detection, tracking and attention-grabbing facial expressions. These results suggest that an embodied curiosity drive may be the progenitor of many social behaviours if satiated by a social environment. This article is part of the theme issue ‘From social brains to social robots: applying neurocognitive insights to human–robot interaction’.