julilili42/papers huggingface dataset:
Metabolic Drug Response Phenotyping in Colorectal Cancer Organoids by LC-QTOF-MS
2020-12-01

As metabolic rewiring is crucial for cancer cell proliferation, metabolic phenotyping of patient-derived organoids is desirable to identify drug-induced changes and trace metabolic vulnerabilities of tumor subtypes. We established a novel protocol for metabolomic and lipidomic profiling of colorectal cancer organoids by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) facing the challenge of capturing metabolic information from a minimal sample amount (&lt;500 cells/injection) in the presence of an extracellular matrix (ECM). The best procedure of the tested protocols included ultrasonic metabolite extraction with acetonitrile/methanol/water (2:2:1, v/v/v) without ECM removal. To eliminate ECM-derived background signals, we implemented a data filtering procedure based on the p-value and fold change cut-offs, which retained features with signal intensities &gt;120% compared to matrix-derived signals present in blank samples. As a proof-of-concept, the method was applied to examine the early metabolic response of colorectal cancer organoids to 5-fluorouracil treatment. Statistical analysis revealed dose-dependent changes in the metabolic profiles of treated organoids including elevated levels of 2′-deoxyuridine, 2′-O-methylcytidine, inosine and 1-methyladenosine and depletion of 2′-deoxyadenosine and specific phospholipids. In accordance with the mechanism of action of 5-fluorouracil, changed metabolites are mainly involved in purine and pyrimidine metabolism. The novel protocol provides a first basis for the assessment of metabolic drug response phenotypes in 3D organoid models.
THESEUS insights into axionlike particles, dark photon, and sterile neutrino dark matter
2020-12-01

Through a series of simulated observations, we investigate the capability of the instruments aboard the forthcoming THESEUS mission for the detection of a characteristic signal from decaying dark matter (DM) in the keV-MeV energy range. We focus our studies on three well studied Standard Model extensions hosting axion-like particle, dark photon, and sterile neutrino DM candidates. We show that, due to the sensitivity of THESEUS' X and Gamma Imaging Spectrometer (XGIS) instrument, existing constraints on dark matter parameters can be improved by a factor of up to ~300, depending on the considered DM model and assuming a zero level of systematic uncertainty. We also show that even a minimal level of systematic uncertainty of 1% can impair potential constraints by one to two orders of magnitude. We argue that nonetheless, the constraints imposed by THESEUS will be substantially better than existing ones and will well complement the constraints of upcoming missions such as eXTP and Athena. Ultimately, the limits imposed by THESEUS and future missions will ensure a robust and thorough coverage of the parameter space for decaying DM models, enabling either a detection of dark matter or a significant improvement of relevant limits.
Gravity and Rotation Drag the Magnetic Field in High-mass Star Formation
2020-12-01

Abstract The formation of hot stars out of the cold interstellar medium lies at the heart of astrophysical research. Understanding the importance of magnetic fields during star formation remains a major challenge. With the advent of the Atacama Large Millimeter Array, the potential to study magnetic fields by polarization observations has tremendously progressed. However, the major question remains how much magnetic fields shape the star formation process or whether gravity is largely dominating. Here, we show that for the high-mass star-forming region G327.3 the magnetic field morphology appears to be dominantly shaped by the gravitational contraction of the central massive gas core where the star formation proceeds. We find that in the outer parts of the region, the magnetic field is directed toward the gravitational center of the region. Filamentary structures feeding the central core exhibit U-shaped magnetic field morphologies directed toward the gravitational center as well, again showing the gravitational drag toward the center. The inner part then shows rotational signatures, potentially associated with an embedded disk, and there the magnetic field morphology appears to be rotationally dominated. Hence, our results demonstrate that for this region gravity and rotation are dominating the dynamics and shaping the magnetic field morphology.
Tweedle proteins form extracellular two-dimensional structures defining body and cell shape in Drosophila melanogaster
2020-12-01

Tissue function and shape rely on the organization of the extracellular matrix (ECM) produced by the respective cells. Our understanding of the underlying molecular mechanisms is limited. Here, we show that extracellular Tweedle (Twdl) proteins in the fruit fly Drosophila melanogaster form two adjacent two-dimensional sheets underneath the cuticle surface and above a distinct layer of dityrosinylated and probably elastic proteins enwrapping the whole body. Dominant mutations in twdl genes cause ectopic spherical aggregation of Twdl proteins that recruit dityrosinylated proteins at their periphery within lower cuticle regions. These aggregates perturb parallel ridges at the surface of epidermal cells that have been demonstrated to be crucial for body shaping. In one scenario, hence, this disorientation of epidermal ridges may explain the squatty phenotype of Twdl mutant larvae. In an alternative scenario, this phenotype may be due to the depletion of the dityrosinylated and elastic layer, and the consequent weakening of cuticle resistance against the internal hydrostatic pressure. According to Barlow's formula describing the distribution of internal pressure forces in pipes in dependence of pipe wall material properties, it follows that this reduction in turn causes lateral expansion at the expense of the antero-posterior elongation of the body.
The Neuromodulator-Encoding sadA Gene Is Widely Distributed in the Human Skin Microbiome
2020-12-01

Trace amines (TA) are endogenously produced in mammals, have a low concentration in the central nervous system (CNS), but trigger a variety of neurological effects and intervene in host cell communication. It emerged that neurotransmitters and TA are produced also by the microbiota. As it has been shown that TA contribute to wound healing, we examined the skin microbiome of probands using shotgun metagenomics. The phyla Actinobacteria, Proteobacteria, Firmicutes, and Bacteroidetes were predominant. Since SadA is a highly promiscuous TA-producing decarboxylase in Firmicutes, the skin microbiome was specifically examined for the presence of sadA -homologous genes. By mapping the reads of certain genes, we found that, although there were less reads mapping to sadA than to ubiquitous housekeeping genes ( arcC and mutS ), normalized reads counts were still &amp;gt;1000 times higher than those of rare control genes ( icaA , icaB , and epiA ). At protein sequence level SadA homologs were found in at least 7 phyla: Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes, Acidobacteria, Chloroflexi, and Cyanobacteria, and in 23 genera of the phylum Firmicutes. A high proportion of the genera that have a SadA homolog belong to the classical skin and intestinal microbiota. The distribution of sadA in so many different phyla illustrates the importance of horizontal gene transfer (HGT). We show that the sadA gene is widely distributed in the human skin microbiome. When comparing the sadA read counts in the probands, there was no correlation between age and gender, but an enormous difference in the sadA read counts in the microbiome of the individuals. Since sadA is involved in TA synthesis, it is likely that the TA content of the skin is correlated with the amount of TA producing bacteria in the microbiome. In this way, the microbiome-generated TA could influence signal transmission in the epithelial and nervous system.
Fire as an Artifact—Advances in Paleolithic Combustion Structure Studies: Introduction to the Special Issue
2020-12-01

Abstract Hearths present sedimentary features, artifacts, and direct evidence for maintained and controlled fire in the past. The use of hearths reflects regular access to fire and its diverse benefits. Among these benefits are cooked food, protection from the cold and from predators, and fire’s transformative power regarding raw materials. Hearths may have also served as focal points of activity at Paleolithic campsites and triggered changes in social structures. As sedimentary features, combustion structures function as behavioral as well as paleoenvironmental archives. The papers in this special issue focus on the former aspect, how combustion feature can serve as transmitters of behavior, and with what tools we can explore them. We here briefly present an overview on the range of topics explored in these papers, which include ethnoarchaeological research on fire use among recent hunter-gatherer groups, spatial analysis of burnt lithics, actualistic experiments regarding fire function and fire use in tool production.
Biochemical and cellular biomarkers in brown trout (Salmo trutta f. fario) in response to the antidepressants citalopram and venlafaxine
2020-12-01

Abstract Background During the last decades, a worldwide increase in the number of cases of depression accompanied by rising prescription rates of antidepressants was recorded. In Germany, the two most prescribed antidepressants are the selective serotonin reuptake inhibitor (SSRI) citalopram and the serotonin and noradrenalin reuptake inhibitor (SNRI) venlafaxine, taking about 30% of the market share. Both antidepressants are found frequently in surface waters and have the potential of adversely affecting aquatic organisms. Most studies dealing with antidepressants address apical endpoints and behaviour; however, only few studies investigate biochemical biomarkers and histopathological alterations. We conducted citalopram and venlafaxine exposure experiments over 5 months, starting with brown trout eggs in the eyed-ova stage, as well as with juvenile brown trout for 4 weeks. Exposure concentrations ranged from environmentally relevant 1 μg/L up to 1 mg/L. In this study, we investigated the effects of the antidepressants on b-esterase activity (neurotoxicity), stress protein level (proteotoxicity) and superoxide dismutase activity (oxidative stress). Additionally, we assessed the health status of the liver by means of histopathological analyses. Results We were able to show that both antidepressants did neither induce proteotoxic nor neurotoxic effects in brown trout. But for venlafaxine, the biochemical biomarker for oxidative stress (superoxide dismutase activity) was significantly increased in larvae exposed to at least 10-μg/L venlafaxine at 7 °C. With regard to liver histopathology, fish exposed to higher citalopram concentrations were in a worse health condition than control fish irrespective of their life stage. Also, the energy storage of fish exposed to 1 mg/L citalopram was reduced. Conclusion Thus, we here report citalopram-dependent histopathological alterations in brown trout liver, and the induction of oxidative stress by venlafaxine.
Directed flow measurement in Pb+Pb collisions at plab = 13A GeV/c collected with NA61/SHINE at SPS
2020-12-01

Abstract We present results of directed flow measurements in Pb+Pb collisions at beam momentum p beam = 13 A GeV/ c recorded at NA61/Shine in 2016. Directed flow is measured relative to the symmetry plane of projectile spectators. Measurements are performed differentially relative to transverse momentum, rapidity and collision centrality. We present v 1 ( p T ) and v 1 ( y ) for protons and negatively charged pions in different centrality classes. The analysis techniques developed as a part of this work will be used for measurements at the future CBM experiment at FAIR and the MPD experiment at NICA.
The transcriptional landscape ofArabidopsis thalianapattern-triggered immunity
2020-12-01

Abstract Plants initiate immunity upon recognition of a wide array of self and non-self molecular patterns. Whether plants tune their immune outputs to patterns of different biological origins or of different biochemical nature remains mostly unclear. Here, we performed a detailed early time-series transcriptomics analysis in Arabidopsis thaliana , revealing that the response to diverse patterns is remarkably congruent. Early transcriptional reprogramming is dominated by a plant general stress response (GSR), which is essential for pattern-induced immunity. The definition of ‘core immunity response’ genes common and specific to pattern response in addition revealed the function of previously uncharacterized GLUTAMATE RECEPTOR-LIKE calcium-permeable channels in immunity. This study thus illustrates general and unique properties of early immune transcriptional reprogramming and uncovered important components of plant immunity. One Sentence Summary Time-resolved transcriptomics reveals new properties of pattern-triggered immunity and function of calcium-permeable channels.
Dialect Identification under Domain Shift: Experiments with Discriminating Romanian and Moldavian
2020-12-01

This paper describes a set of experiments for discriminating between two closely related language varieties, Moldavian and Romanian, under a substantial domain shift. The experiments were conducted as part of the Romanian dialect identification task in the VarDial 2020 evaluation campaign. Our best system based on linear SVM classifier obtained the first position in the shared task with an F1 score of 0.79, supporting the earlier results showing (unexpected) success of machine learning systems in this task. The additional experiments reported in this paper also show that adapting to the test set is useful when the training data comes from another domain. However, the benefit of adaptation becomes doubtful even when a small amount of data from the target domain is available.
The Effects of a University’s Self-Presentation and Applicants’ Regulatory Focus on Emotional, Behavioral, and Cognitive Student Engagement
2020-12-01

A university’s presentation of its programs to the public should provide potential students with information about what they can expect as students at that university. However, it is largely unclear what kind of self-presentation affects different applicants and their commitment. In a laboratory experiment with N = 116 participants, we examined the emotional, behavioral and cognitive impact of a university’s self-presentation (either emphasizing chances for students or emphasizing their obligations) on student engagement. We also measured the participants’ regulatory focus (promotion and prevention focus). We found interaction effects of the university’s self-presentation and participants’ promotion and prevention focus on student engagement. There was a regulatory fit for promotion focus in the chances condition for emotions and behavior. There was also a regulatory fit for prevention focus in the obligations condition for cognitive processes. We conclude that universities should dedicate time and effort to creating a clear presentation of their offerings in the implementation of digital learning environments.
Residual Axillary Burden After Neoadjuvant Chemotherapy (NACT) in Early Breast Cancer in Patients with a priori Clinically Occult Nodal Metastases – a transSENTINA Analysis
2020-12-01

Abstract Background Among patients with breast cancer undergoing neoadjuvant chemotherapy (NACT), the association between pathological complete remission (pCR) in the breast and clinical/pathological parameters is well established, whereas the association between these parameters and residual axillary involvement after NACT remains unclear. Methods Patients with clinically occult nodal metastases (i.e. negative by clinical assessment but positive by SLNB prior to NACT, i.e. Arm B of the SENTINA trial) were included in the presented analysis. All patients received a second sentinel lymph node biopsy (SLNB) and axillary dissection after NACT. Univariate and multivariate analyses were carried out to evaluate the association between clinical/pathological parameters and axillary involvement after NACT. Results Arm B of the SENTINA study contained 360 patients, 318 of which were evaluable for this analysis. After NACT, 71/318 (22.3%) patients had involved SLNs or non-SLNs after NACT. Overall, 71/318 (22.3%) patients achieved a pCR in the breast. Associations of extranodal spread, lack of multifocality and pCR in the breast with residual axillary burden were statistically significant. In a descriptive analysis including all patients with clinically negative axilla before NACT in the SENTINA trial 1.2% of triple negative (TN) patients and 0.5% of HER/2 positive patients had residual axillary disease in case of a breast pCR. Conclusions Patients in the SENTINA trial with clinically negative axilla and involved SLNs still carried a significant risk of nodal metastases after NACT. However, the risk of residual axillary burden was particularly low in TN and HER/2 positive tumors in case of a breast pCR.
Early Neolithic settlement Ilindentsi in the Middle Struma valley, south–western Bulgaria: spatial organization and pottery
2020-12-01

The article offers new data on the Neolithisation process in the Struma valley and the Central Balkans based on recent research at the Early Neolithic settlement Ilindentsi in southwestern Bulgaria. The settlement was inhabited during the second half of the Early Neolithic. The stratigraphic analysis points to at least two main periods, which belong respectively to the Early Neolithic (Ilindentsi I) and the Middle Neolithic (Ilindentsi II). The entire ceramic assemblage shows a very smooth transition from the Early to the Middle Neolithic with two transitional stages of the final Early Neolithic – Ilindentsi FEN I and Ilindentsi FEN II. The results of this multidisciplinary study show the complexity of the processes related to the Neolithisation of this part of southeast Europe and the diversity of factors influencing the foundation and development of Ilindentsi, as well as its place in the network of early Neolithic settlements in the Balkans.
Object-oriented lexical encoding of multiword expressions: Short and sweet
2020-12-01

Multiword expressions (MWEs) exhibit both regular and idiosyncratic properties. Their idiosyncrasy requires lexical encoding in parallel with their component words. Their (at times intricate) regularity, on the other hand, calls for means of flexible factorization to avoid redundant descriptions of shared properties. However, so far, non-redundant general-purpose lexical encoding of MWEs has not received a satisfactory solution. We offer a proof of concept that this challenge might be effectively addressed within eXtensible MetaGrammar (XMG), an object-oriented metagrammar framework. We first make an existing metagrammatical resource, the FrenchTAG grammar, MWE-aware. We then evaluate the factorization gain during incremental implementation with XMG on a dataset extracted from an MWE-annotated reference corpus.
Eye Tracking Data Collection Protocol for VR for Remotely Located Subjects using Blockchain and Smart Contracts
2020-12-01

Eye tracking data collection in the virtual reality context is typically\\ncarried out in laboratory settings, which usually limits the number of\\nparticipants or consumes at least several months of research time. In addition,\\nunder laboratory settings, subjects may not behave naturally due to being\\nrecorded in an uncomfortable environment. In this work, we propose a\\nproof-of-concept eye tracking data collection protocol and its implementation\\nto collect eye tracking data from remotely located subjects, particularly for\\nvirtual reality using Ethereum blockchain and smart contracts. With the\\nproposed protocol, data collectors can collect high quality eye tracking data\\nfrom a large number of human subjects with heterogeneous socio-demographic\\ncharacteristics. The quality and the amount of data can be helpful for various\\ntasks in data-driven human-computer interaction and artificial intelligence.\\n
The Relationship between Mobility and COVID-19 in Germany: Modeling Case Occurrence using Apple's Mobility Trends Data
2020-12-01

Abstract Background Restrictions on social interaction and movement were implemented by the German government in March 2020 to reduce the transmission of coronavirus disease 2019 (COVID-19). Apple's “Mobility Trends” (AMT) data details levels of community mobility; it is a novel resource of potential use to epidemiologists. Objective The aim of the study is to use AMT data to examine the relationship between mobility and COVID-19 case occurrence for Germany. Is a change in mobility apparent following COVID-19 and the implementation of social restrictions? Is there a relationship between mobility and COVID-19 occurrence in Germany? Methods AMT data illustrates mobility levels throughout the epidemic, allowing the relationship between mobility and disease to be examined. Generalized additive models (GAMs) were established for Germany, with mobility categories, and date, as explanatory variables, and case numbers as response. Results Clear reductions in mobility occurred following the implementation of movement restrictions. There was a negative correlation between mobility and confirmed case numbers. GAM using all three categories of mobility data accounted for case occurrence as well and was favorable (AIC or Akaike Information Criterion: 2504) to models using categories separately (AIC with “driving,” 2511. “transit,” 2513. “walking,” 2508). Conclusion These results suggest an association between mobility and case occurrence. Further examination of the relationship between movement restrictions and COVID-19 transmission may be pertinent. The study shows how new sources of online data can be used to investigate problems in epidemiology.
Using multiplicity of produced particles for centrality determination in heavy-ion collisions with the CBM experiment
2020-12-01

Abstract The evolution of matter created in a heavy-ion collision depends on its initial geometry. Experimentally collision geometry is characterized with centrality. Procedure of centrality determination for the Compressed Baryonic Matter (CBM) experiment at FAIR is presented. Relation between parameters of the collision geometry (such as impact parameter magnitude) and centrality classes is extracted using multiplicity of produced charged particles. The latter is connected to the collision geometry parameters using Monte-Carlo Glauber approach.