Miracle-dz/UniFAR-FTUs huggingface dataset:
Hans B. Pacejka (1934–2017): a life in tyre mechanics

Hans Pacejka was born in the city of Rotterdam in the Netherlands, on 12 September 1934, in an Austrian family. His parents, Eduard S. Pacejka and Edith Messmer, were originally from Vienna and emigrated to the Netherlands in 1932. His father, Eduard, was already familiar with the Netherlands through a World War I humanitarian children’s act. After that war, ill-fed Austrian children were sent to foster parents in the Netherlands for nourishment. After Eduard finished his secondary school in the Netherlands, he went back to Austria to study mechanical engineering at the Vienna University of Technology. Directly after graduation, he married Edith Messmer and started looking for a job. In the meantime, his foster parents from the Netherlands were working at the TMS Technicum in Rotterdam, a polytechnical school oriented towards an engineering education. They offered Eduard a job as a teacher at the Technicum, and in 1932, Eduard and Edith emigrated to the Netherlands. In that same year, they were naturalised, and in 1933, their first child, Edith Marijke Pacejka, was born. The next year, 1934, Hans Bastiaan Pacejka was born. After having finished primary school, partly through home education because ofWorld War II, Hans started his secondary school education in Rotterdam at the Erasmiaans Gymnasium in 1946. In 1948, his father was offered a professorship in mechanical engineering at the Technical University of Bandung, and the family moved to what is now Indonesia in
Determination of Bacterioplankton Abundance, Production and Carbon Budget in the Northwest Weddell Sea

Abstract Bacteria are an essential part of the microbial loops and play key roles in carbon cycling. To understand their ecological contributions in polar regions, they were measured in the northwest Weddell Sea during the 32nd Chinese National Antarctic Research Expedition in the austral summer of 2016. The results showed a range of bacterial abundance from 0.20 to 3.34 × 108 cells/L with an average of 1.03 × 108 cells/dm3. Bacterial production varied between 0.06 and 2.42 mg C/(m3 d) with an average of 0.44 mg C/(m3 d). Bacterial carbon budgets were unevenly distributed in the northwest Weddle Sea, and surpluses appeared in the autotrophic area such as Weddell Surface Water and Transitional Zonal Water with Weddell Sea influence (TWW), and deficits in the Weddell-Scotia Confluence (heterotrophic area). A t-test result suggested that the unbalanced bacterial carbon budgets were mainly caused by distributions of Chl a. Bacterial abundance was uncorrelated with environmental and biological factors in the autotrophic region. At the same time, production was positively correlated with temperature and Chl a. In the heterotrophic area, bacterial abundance was positively correlated with temperature. Production was significantly positively correlated with temperature, and Chl a. Bacterial production had a small contribution to the increase of bacterial abundance because of a strong top-down control in the northwest Weddell Sea.
Behavioral Thermoregulation by Mothers Protects Offspring from Global Warming but at a Cost

Thermal conditions during embryonic development affect offspring phenotype in ectotherms. Therefore, rising environmental temperatures can have important consequences for an individual’s fitness. Nonetheless, females have some capacity to compensate for potential negative consequences that adverse developmental environments may have on their offspring. Recent studies show that oviparous reptiles exhibit behavioral plasticity in nest site selection, which can buffer their embryos against high incubation temperatures; however, much less is known about these responses in viviparous reptiles. We subjected pregnant viviparous skinks, Saiphos equalis, to current or projected midcentury (2050) temperatures to test (i) how elevated temperatures affect female thermoregulatory and foraging behavior; (ii) whether temperatures experienced by females during pregnancy negatively affect the morphology, performance, and behavior of hatchlings; and (iii) whether behavioral thermoregulation during pregnancy is costly to females. Females from the elevated temperature treatment compensated by going deeper belowground to seek cooler temperatures and eating less, and they consequently had a lower body mass relative to snout-to-vent length (condition estimator) compared with females from the current thermal treatment. The temperatures experienced by females in the elevated temperature treatment were high enough to affect foraging and locomotor performance but not the morphology and growth rate of hatchlings. By seeking cooler temperatures, mothers can mitigate some of the effects of high temperatures on their offspring (e.g., reduced body size and growth). However, this protective behavior of females may come at an energetic cost to them. This study adds to growing evidence of lizards’ vulnerability to global warming, particularly during reproduction when females are already paying a substantial cost.
Preliminary Evidence for Cannabis and Nicotine Urinary Metabolites as Predictors of Verbal Memory Performance and Learning Among Young Adults

Abstract Objective: Verbal memory deficits are linked to cannabis use. However, self-reported episodic use does not allow for assessment of variance from other factors (e.g., cannabis potency, route of consumption) that are important for assessing brain-behavior relationships. Further, co-occurring nicotine use may moderate the influence of cannabis on cognition. Here we utilized objective urinary measurements to assess the relationship between metabolites of cannabis, 11-nor-9-carboxy-∆9-tetrahydrocannabinol (THCCOOH), and nicotine (cotinine) on verbal memory in young adults. Method: Adolescents and young adults (n = 103) aged 16–22 completed urinary drug testing and verbal memory assessment (RAVLT). Linear regressions examined the influence of THCCOOH and cotinine quantitative concentrations, and their interaction, on RAVLT scores, controlling for demographics and alcohol. Cannabis intake frequency was also investigated. Secondary analyses examined whether past month or recency of use related to performance, while controlling for THCCOOH and cotinine concentrations. Results: THCCOOH concentration related to both poorer total learning and long delay recall. Cotinine concentration related to poorer short delay recall. Higher frequency cannabis use status was associated with poorer initial learning and poorer short delay. When comparing to self-report, THCCOOH and cotinine concentrations were negatively related to learning and memory performance, while self-report was not. Conclusions: Results confirm the negative relationship between verbal memory and cannabis use, extending findings with objective urinary THCCOOH, and cotinine concentration measurements. No moderating relationship with nicotine was found, though cotinine concentration independently associated with negative short delay performance. Findings support the use of both urinary and self-report metrics as complementary methods in substance use research.
Characterizing cancer‐associated myosteatosis: anatomic distribution and cancer‐specific variability of low radiodensity muscle

Low muscle radiodensity on computed tomography (CT) scan, indicative of myosteatosis, is commonly observed in cancer patients and can be associated with poor prognosis. Radiodensity is typically measured at the level of the third lumbar vertebra (L3). It is unknown whether features at L3 reflect a systemic state affecting peripheral muscle groups, whether images used at different levels can be used as a surrogate if L3 images are unavailable, and how radiodensity varies between cancer types.
Parallel Framework for Inferring Genome Scale Gene Regulatory Networks

Genome-scale network inference is essential to understand comprehensive interaction patterns. Current methods are limited to the reconstruction of small to moderate-size networks. The most obvious alternative is to propose a novel method or alter existing methods that may leverage parallel computing paradigms. Very few attempts also have been made to re-engineer existing methods by executing selective iterative steps concurrently. We propose a generic framework in this paper that leverages parallel computing without re-engineering the original methods. The proposed framework uses state-of-the-art methods as a black box to infer sub-networks of the segmented data matrix. A simple merger was designed based on preferential attachment to generate the global network by merging the sub-networks. Fifteen (15) inference methods were considered for experimentation. Qualitative and speedup analysis was carried out using DREAM challenge networks. The proposed framework was implemented on all the 15 inference methods using large expression matrices. The results were auspicious as we could infer large networks in reasonable time without compromising the qualitative aspects of the original (serial) algorithm. CLR, the top performer, was then used to infer the network from the expression profiles of an Alzheimer’s disease (AD) affected mouse model consisting of 45,101 genes. We have also highlighted few hub genes from the network that are functionally related to various diseases.
Cellular remodeling and JAK inhibition promote zygotic gene expression in the Ciona germline

During development, remodeling of the cellular transcriptome and proteome underlies cell fate decisions and, in somatic lineages, transcription control is a major determinant of fateful biomolecular transitions. By contrast, early germline fate specification in numerous vertebrate and invertebrate species relies extensively on RNA-level regulation, exerted on asymmetrically inherited maternal supplies, with little-to-no zygotic transcription. However delayed, a maternal-to-zygotic transition is nevertheless poised to complete the deployment of pre-gametic programs in the germline. Here, we focused on early germline specification in the tunicate Ciona to study zygotic genome activation. We first demonstrate that a peculiar cellular remodeling event excludes localized postplasmic mRNAs, including Pem-1, which encodes the general inhibitor of transcription. Subsequently, zygotic transcription begins in Pem-1-negative primordial germ cells (PGCs), as revealed by histochemical detection of elongating RNA Polymerase II (RNAPII), and nascent transcripts from the Mef2 locus. Using PGC-specific Mef2 transcription as a read-out, we uncovered a provisional antagonism between JAK and MEK/BMPRI/GSK3 signaling, which controls the onset of zygotic gene expression, following cellular remodeling of PGCs. We propose a 2-step model for the onset of zygotic transcription in the Ciona germline, which relies on successive cellular remodeling and JAK inhibition, and discuss the significance of germ plasm dislocation and remodeling in the context of developmental fate specification.
Rapid Shifts in Mitochondrial tRNA Import in a Plant Lineage with Extensive Mitochondrial tRNA Gene Loss

In most eukaryotes, transfer RNAs (tRNAs) are one of the very few classes of genes remaining in the mitochondrial genome, but some mitochondria have lost these vestiges of their prokaryotic ancestry. Sequencing of mitogenomes from the flowering plant genus Silene previously revealed a large range in tRNA gene content, suggesting rapid and ongoing gene loss/replacement. Here, we use this system to test longstanding hypotheses about how mitochondrial tRNA genes are replaced by importing nuclear-encoded tRNAs. We traced the evolutionary history of these gene loss events by sequencing mitochondrial genomes from key outgroups (Agrostemma githago and Silene [=Lychnis] chalcedonica). We then performed the first global sequencing of purified plant mitochondrial tRNA populations to characterize the expression of mitochondrial-encoded tRNAs and the identity of imported nuclear-encoded tRNAs. We also confirmed the utility of high-throughput sequencing methods for the detection of tRNA import by sequencing mitochondrial tRNA populations in a species (Solanum tuberosum) with known tRNA trafficking patterns. Mitochondrial tRNA sequencing in Silene revealed substantial shifts in the abundance of some nuclear-encoded tRNAs in conjunction with their recent history of mt-tRNA gene loss and surprising cases where tRNAs with anticodons still encoded in the mitochondrial genome also appeared to be imported. These data suggest that nuclear-encoded counterparts are likely replacing mitochondrial tRNAs even in systems with recent mitochondrial tRNA gene loss, and the redundant import of a nuclear-encoded tRNA may provide a mechanism for functional replacement between translation systems separated by billions of years of evolutionary divergence.
Mutation rate and spectrum in Caenorhabditis elegans mutation accumulation lines subjected to RNAi-induced knockdown of the mismatch repair gene msh-2

DNA mismatch repair (MMR), an evolutionarily conserved repair pathway shared by prokaryotic and eukaryotic species alike, influences molecular evolution by detecting and correcting mismatches that escape DNA polymerase proofreading, thereby protecting genetic fidelity, reducing the mutational load, and preventing lethality. Herein we conduct the first genome-wide evaluation of the alterations to the mutation rate and spectrum under impaired activity of the MutSα homolog, msh-2, in Caenorhabditis elegans. We performed mutation accumulation (MA) under RNAi-induced knockdown of msh-2 for 50 generations in obligately outcrossing fog-2(lf) lines, followed by next-generation sequencing of 19 MA lines and the ancestral control. msh-2 impairment substantially increased the frequency of nuclear base substitutions (∼23×) and small indels (∼328×) relative to wildtype. However, we observed no increase in the mutation rates of mtDNA, and copy-number changes of single-copy genes. There was a marked increase in copy-number variation of rDNA genes under MMR impairment. In C. elegans, msh-2 repairs transitions more efficiently than transversions as well as increases the AT mutational bias relative to wildtype. The local sequence context, including sequence complexity, G+C-content, and flanking bases influenced the mutation rate. The X chromosome had a lower substitution and higher indel rate than autosomes, which can either result from sex-specific mutation rates or a nonrandom distribution of mutable sites in the genome. Comparison of MMR impairment in C. elegans to that in other species shows that the specificity of the MMR varies between taxa, and is more efficient in detecting and repairing small indels in eukaryotes relative to prokaryotes.
The functional form of specialized predation dramatically affects whether Janzen-Connell effects can prevent competitive exclusion

Janzen Connell Effects (JCEs), specialized predation of seeds and seedlings near conspecific trees, are hypothesized to promote high species richness. While past modeling studies show JCEs can maintain higher diversity than a neutral community, recent theoretical work indicates JCEs may weakly inhibit competitive exclusion when species exhibit interspecific fitness variation. However, recent models make somewhat restrictive assumptions about the functional form of specialized predation – that JCEs occur at a fixed rate when seeds/seedlings are within a fixed distance of a conspecific tree. Using a theoretical model, I show that the functional form of JCEs largely impacts their ability to promote coexistence. If specialized predation pressure increases additively with adult tree density and decays exponentially with distance, JCEs maintain considerably higher diversity than predicted by recent models. Parameterizing the model with values from a Panamanian tree community indicates JCEs can maintain high diversity in communities exhibiting high interspecific fitness variation.
Zic1 advances epaxial myotome morphogenesis to cover the neural tube via Wnt11r

The dorsal axial muscles, or epaxial muscles, are a fundamental structure covering the spinal cord and vertebrae, as well as mobilizing the vertebrate trunk. To date, mechanisms underlying the morphogenetic process shaping the epaxial myotome are largely unknown. To address this, we used the medaka zic1/zic4-enhancer mutant Double anal fin (Da), which exhibits ventralized dorsal trunk structures resulting in impaired epaxial myotome morphology and incomplete coverage over the neural tube. In wild type, dorsal dermomyotome (DM) cells, progenitors of myotomal cells, reduce their proliferative activity after somitogenesis and subsequently form unique large protrusions extending dorsally, potentially guiding the epaxial myotome dorsally. In Da, by contrast, DM cells maintain the high proliferative activity and form mainly small protrusions. By combining RNA- and ChIP-sequencing analyses, we revealed direct targets of Zic1 which are specifically expressed in dorsal somites and involved in various aspects of development, such as cell migration, extracellular matrix organization and cell-cell communication. Among these, we identified wnt11r as a crucial factor regulating both cell proliferation and protrusive activity of DM cells. We propose that the dorsal movement of the epaxial myotome is guided by DM cells and that Zic1 empowers this activity via Wnt11r to achieve the neural tube coverage.
Scanning mutagenesis of RNA-binding protein ProQ reveals a quality control role for the Lon protease

The FinO-domain protein ProQ belongs to a widespread family of RNA-binding proteins (RBPs) involved in gene regulation in bacterial chromosomes and mobile elements. Whilst the cellular RNA targets of ProQ have been established in diverse bacteria, the functionally crucial ProQ residues remain to be identified under physiological conditions. Following our discovery that ProQ deficiency alleviates growth suppression of Salmonella with succinate as the sole carbon source, an experimental evolution approach was devised to exploit this phenotype. By coupling mutational scanning with loss-of-function selection, we identified multiple ProQ residues in both the N-terminal FinO domain and the variable C-terminal region required for ProQ activity. Two C-terminal mutations abrogated ProQ function and mildly impaired binding of a model RNA target. By contrast, several mutations in the FinO domain rendered ProQ both functionally inactive and unable to interact with target RNA in vivo. Alteration of the FinO domain stimulated the rapid turnover of ProQ by Lon-mediated proteolysis, suggesting a quality control mechanism that prevents the accumulation of non-functional ProQ molecules. We extend this observation to Hfq, the other major sRNA chaperone of enteric bacteria. The Hfq Y55A mutant protein, defective in RNA-binding and oligomerization, proved to be labile and susceptible to degradation by Lon. Taken together, our findings connect the major AAA+ family protease Lon with RNA-dependent quality control of Hfq and ProQ, the two major sRNA chaperones of Gram-negative bacteria. SIGNIFICANCE Proteins that interact with RNA play a vital role in controlling key functions in pathogenic bacteria. RNA-binding proteins regulate how, when and where bacteria feed, swim or interact with a host, and it is critical that we understand how RNAs associate with these proteins. ProQ is one of the three major RNA-binding proteins (RBPs) in Gram-negative bacteria. In this study, we mapped the amino acid residues of ProQ that are essential for function. We successfully identified residue substitutions that rendered the ProQ RBP both non-functional and unable to interact with RNA. Our findings raise the possibility that the Lon protease mediates a quality control mechanism of ProQ that targets this RBP in the absence of RNA. A posttranslational quality control mechanism of this type could prevent the accumulation of nonfunctional RBPs in the bacterial cytoplasm.
Modelling complex population structure using F-statistics and Principal Component Analysis

Human genetic diversity is shaped by our complex history. Data-driven methods such as Principal Component Analysis (PCA) are an important population genetic tool to understand this method. Here, I contrast PCA with a set of statistics motivated by trees (F-statistics). Here, I show that these two methods are closely related, and I derive explicit connections between the two approaches. I show that F-statistics have a simple geometrical interpretation in the context of PCA, and that orthogonal projections are the key concept to establish this link. I illustrate my results on two examples, one of local, and one of global human diversity. In both examples, I find that just using the first few PCs provides good population structure is sparse, and only a few components contribute to most statistics. Based on these results, I develop novel visualizations that allow for investigating specific hypotheses, checking the assumptions of more sophisticated models. My results extend F-statistics to non-discrete populations, moving towards more complete and less biased descriptions of human genetic variation.
Experimental evolution of Vibrio cholerae: Identification of genes involved in motility in presence of polymyxin B

Vibrio cholerae is the bacteria responsible for the cholera disease and a natural inhabitant of aquatic environments. Biofilm formation is important for human colonization and environmental survival. Motility is essential for adhesion and biofilm formation by V. cholerae. In a previous study, we showed that motility and biofilm formation are altered in the presence of sub-inhibitory concentrations of polymyxin B in V. cholerae. In this study, we performed an experimental evolution to identify genes rescuing the motility in the presence of polymyxin B. Mutations in 5 genes have been identified: ihfA, vacJ (mlaA), mlaF, dacB and ccmH. The details of these mutations, their potential impact on the function of the proteins they encode and on the motility in presence of polymyxin B are discussed.
Interpretable machine learning models for single-cell ChIP-seq imputation

Motivation Single-cell ChIP-seq (scChIP-seq) analysis is challenging due to data sparsity. High degree of data sparsity in biological high-throughput single-cell data is generally handled with imputation methods that complete the data, but specific methods for scChIP-seq are lacking. We present SIMPA, a scChIP-seq data imputation method leveraging predictive information within bulk data from ENCODE to impute missing protein-DNA interacting regions of target histone marks or transcription factors. Results Imputations using machine learning models trained for each single cell, each target, and each genomic region accurately preserve cell type clustering and improve pathway-related gene identification on real data. Results on simulated data show that 100 input genomic regions are already enough to train single-cell specific models for the imputation of thousands of undetected regions. Furthermore, SIMPA enables the interpretation of machine learning models by revealing interaction sites of a given single cell that are most important for the imputation model trained for a specific genomic region. The corresponding feature importance values derived from promoter-interaction profiles of H3K4me3, an activating histone mark, highly correlate with co-expression of genes that are present within the cell-type specific pathways. An imputation method that allows the interpretation of the underlying models facilitates users to gain an even deeper understanding of individual cells and, consequently, of sparse scChIP-seq datasets. Availability and implementation Our interpretable imputation algorithm was implemented in Python and is available at https://github.com/salbrec/SIMPA