julilili42/papers huggingface dataset:
Gap, shadows, spirals, and streamers: SPHERE observations of binary-disk interactions in GG Tauri A
2020-05-29

Context. A large portion of stars is found to be part of binary or higher-order multiple systems. The ubiquity of planets found around single stars raises the question of whether and how planets in binary systems form. Protoplanetary disks are the birthplaces of planets, and characterizing them is crucial in order to understand the planet formation process. Aims. Our goal is to characterize the morphology of the GG Tau A disk, one of the largest and most massive circumbinary disks. We also aim to trace evidence for binary-disk interactions. Methods. We obtained observations in polarized scattered light of GG Tau A using the SPHERE/IRDIS instrument in the H -band filter. We analyzed the observed disk morphology and substructures. We ran 2D hydrodynamical models to simulate the evolution of the circumbinary ring over the lifetime of the disk. Results. The disk and also the cavity and the inner region are highly structured, with several shadowed regions, spiral structures, and streamer-like filaments. Some of these are detected here for the first time. The streamer-like filaments appear to connect the outer ring with the northern arc. Their azimuthal spacing suggests that they may be generated through periodic perturbations by the binary, which tear off material from the inner edge of the outer disk once during each orbit. By comparing observations to hydrodynamical simulations, we find that the main features, in particular, the gap size, but also the spiral and streamer filaments, can be qualitatively explained by the gravitational interactions of a binary with a semimajor axis of ~35 au on an orbit coplanar with the circumbinary ring.
Pupil diameter differentiates expertise in dental radiography visual search
2020-05-29

Expert behavior is characterized by rapid information processing abilities, dependent on more structured schemata in long-term memory designated for their domain-specific tasks. From this understanding, expertise can effectively reduce cognitive load on a domain-specific task. However, certain tasks could still evoke different gradations of load even for an expert, e.g., when having to detect subtle anomalies in dental radiographs. Our aim was to measure pupil diameter response to anomalies of varying levels of difficulty in expert and student dentists' visual examination of panoramic radiographs. We found that students' pupil diameter dilated significantly from baseline compared to experts, but anomaly difficulty had no effect on pupillary response. In contrast, experts' pupil diameter responded to varying levels of anomaly difficulty, where more difficult anomalies evoked greater pupil dilation from baseline. Experts thus showed proportional pupillary response indicative of increasing cognitive load with increasingly difficult anomalies, whereas students showed pupillary response indicative of higher cognitive load for all anomalies when compared to experts.
Subunits of BK channels promote breast cancer development and modulate responses to endocrine treatment in preclinical models
2020-05-29

Background and Purpose Pore‐forming α subunits of the voltage‐ and Ca 2+ ‐activated K + channel with large conductance (BKα) promote malignant phenotypes of breast tumour cells. Auxiliary subunits such as the leucine‐rich repeat containing 26 (LRRC26) protein, also termed BKγ1, may be required to permit activation of BK currents at a depolarized resting membrane potential that frequently occur in non‐excitable tumour cells. Experimental Approach Anti‐tumour effects of BKα loss were investigated in breast tumour‐bearing MMTV‐PyMT transgenic BKα knockout (KO) mice, primary MMTV‐PyMT cell cultures, and in a syngeneic transplantation model of breast cancer derived from these cells. The therapeutic relevance of BK channels in the context of endocrine treatment was assessed in human breast cancer cell lines expressing either low (MCF‐7) or high (MDA‐MB‐453) levels of BKα and BKγ1, as well as in BKα‐negative MDA‐MB‐157. Key Results BKα promoted breast cancer onset and overall survival in preclinical models. Conversely, lack of BKα and/or knockdown of BKγ1 attenuated proliferation of murine and human breast cancer cells in vitro. At low concentrations, tamoxifen and its major active metabolites stimulated proliferation of BKα/γ1‐positive breast cancer cells, independent of the genomic signalling controlled by the oestrogen receptor. Finally, tamoxifen increased the relative survival time of BKα KO but not of wild‐type tumour cell recipient mice. Conclusion and Implications Breast cancer initiation, progression, and tamoxifen sensitivity depend on functional BK channels thereby providing a rationale for the future exploration of the oncogenic actions of BK channels in clinical outcomes with anti‐oestrogen therapy. LINKED ARTICLES This article is part of a themed issue on New avenues in cancer prevention and treatment (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.12/issuetoc
Distinct immune evasion in APOBEC‐enriched, HPV‐negative HNSCC
2020-05-29

Abstract Immune checkpoint inhibition leads to response in some patients with head and neck squamous cell carcinoma (HNSCC). Robust biomarkers are lacking to date. We analyzed viral status, gene expression signatures, mutational load and mutational signatures in whole exome and RNA‐sequencing data of the HNSCC TCGA dataset (n = 496) and a validation set (DKTK MASTER cohort, n = 10). Public single‐cell gene expression data from 17 HPV‐negative HNSCC were separately reanalyzed. APOBEC3‐associated TCW motif mutations but not total single nucleotide variant burden were significantly associated with inflammation. This association was restricted to HPV‐negative HNSCC samples. An APOBEC‐enriched, HPV‐negative subgroup was identified, that showed higher T‐cell inflammation and immune checkpoint expression, as well as expression of APOBEC3 genes. Mutations in immune‐evasion pathways were also enriched in these tumors. Analysis of single‐cell sequencing data identified expression of APOBEC3B and 3C genes in malignant cells. We identified an APOBEC‐enriched subgroup of HPV‐negative HNSCC with a distinct immunogenic phenotype, potentially mediating response to immunotherapy.
Changes in the perception of upright body orientation with age
2020-05-29

To determine own upright body orientation the brain creates a sense of verticality by a combination of multisensory inputs. To test whether this process is affected by aging, we placed younger and older adults on a motion platform and systematically tilted the orientation of their visual surroundings by using an augmented reality setup. In a series of trials, participants adjusted the orientation of the platform until they perceived themselves to be upright. Tilting the visual scene around the roll axis induced a bias in subjective postural vertical determination in the direction of scene tilt in both groups. In the group of older participants, however, the observed peak bias was larger and occurred at larger visual tilt angles. This indicates that the susceptibility to visually induced biases increases with age, possibly caused by a reduced reliability of sensory information.
Sevoflurane depletes macrophages from the melanoma microenvironment
2020-05-29

In sharp contrast to the detrimental impact of sevoflurane on patients' outcome reported in retrospective clinical studies, we propose here that sevoflurane might actually exert a beneficial effect by decreasing TAMs within the TME, rendering the tumour again susceptible for cytotoxic T cells and immunotherapies. Further research is warranted to delineate, how these results translate into the clinic.
Identification of a conserved var gene in different Plasmodium falciparum strains
2020-05-29

Abstract Background The multicopy var gene family of Plasmodium falciparum is of crucial importance for pathogenesis and antigenic variation. So far only var2csa, the var gene responsible for placental malaria, was found to be highly conserved among all P. falciparum strains. Here, a new conserved 3D7 var gene (PF3D7_0617400) is identified in several field isolates. Methods DNA sequencing, transcriptional analysis, Cluster of Differentiation (CD) 36-receptor binding, indirect immunofluorescence with PF3D7_0617400-antibodies and quantification of surface reactivity against semi-immune sera were used to characterize an NF54 clone and a Gabonese field isolate clone (MOA C3) transcribing the gene. A population of 714 whole genome sequenced parasites was analysed to characterize the conservation of the locus in African and Asian isolates. The genetic diversity of two var2csa fragments was compared with the genetic diversity of 57 microsatellites fragments in field isolates. Results PFGA01_060022400 was identified in a Gabonese parasite isolate (MOA) from a chronic infection and found to be 99% identical with PF3D7_0617400 of the 3D7 genome strain. Transcriptional analysis and immunofluorescence showed expression of the gene in an NF54 and a MOA clone but CD36 binding assays and surface reactivity to semi-immune sera differed markedly in the two clones. Long-read Pacific bioscience whole genome sequencing showed that PFGA01_060022400 is located in the internal cluster of chromosome 6. The full length PFGA01_060022400 was detected in 36 of 714 P. falciparum isolates and 500 bp fragments were identified in more than 100 isolates. var2csa was in parts highly conserved (H e = 0) but in other parts as variable (H e = 0.86) as the 57 microsatellites markers (H e = 0.8). Conclusions Individual var gene sequences exhibit conservation in the global parasite population suggesting that purifying selection may limit overall genetic diversity of some var genes. Notably, field and laboratory isolates expressing the same var gene exhibit markedly different phenotypes.
Functional-Style SQL UDFs With a Capital 'F'
2020-05-29

We advocate to express complex in-database computation using a functional style in which SQL UDFs use plain self-invocation to recurse. The resulting UDFs are concise and readable, but their run time performance on contemporary RDBMSs is sobering. This paper describes how to compile such functional-style UDFs into SQL:1999 recursive common table expressions. We build on function call graphs to build the compiler's core and to realize a series of optimizations (reference counting, memoization, exploitation of linear and tail recursion). The compiled UDFs evaluate efficiently, challenging the performance of manually tweaked (but often convoluted) SQL code. SQL UDFs can indeed be functional and fast.
PL/SQL Without the PL
2020-05-29

We demonstrate a source-to-source compilation technique that can translate user-defined PL/SQL functions into plain SQL queries. These PL/SQL functions may feature arbitrarily complex control flow-iteration, in particular. From this imperative-style input code we derive equivalent recursive common table expressions, ready for execution on any relational SQL:1999 back-end. Principally due to the absence of PL/SQL?SQL context switches, the output plain SQL code comes with substantial runtime savings. The demonstration embeds the compiler into an interactive setup that admits function editing while live re-compilation and visualization of intermediate code forms happens in the background.
Efficacy of Adalimumab in Non-Infectious Uveitis Across Different Etiologies: A Post Hoc Analysis of the VISUAL I and VISUAL II Trials
2020-05-29

<b>Purpose</b>: To assess efficacy of adalimumab versus placebo in patients with active or inactive noninfectious intermediate, posterior, or panuveitis across different etiologies.<b>Methods</b>: VISUAL I (V-I) and VISUAL II (V-II) clinical trials included adults with active or inactive uveitis, respectively, randomized to receive adalimumab or placebo. In a post hoc subgroup analysis, time to treatment failure (TTF) starting at week 6 (V-I) or week 2 (V-II) was analyzed using the Kaplan-Meier method. Hazard ratios (HR) for TTF with 95% CI were calculated with Cox proportional hazards regression.<b>Results</b>: The analysis included 217 V-I patients and 226 V-II patients. Treatment failure occurred later and risk was significantly lower in patients with idiopathic uveitis receiving adalimumab versus those receiving placebo in V-I (HR = 0.50 [CI, 0.30-0.84]; <i>P</i> = .006) and V-II (HR = 0.43 [CI, 0.22-0.83]; <i>P</i> = .010).<b>Conclusions</b>: Treatment failure risk was lower in patients with idiopathic noninfectious uveitis receiving adalimumab versus those receiving placebo.
Accurate determination of γδ T cells in multi‐channel mass and flow cytometry
2020-05-29

Cytometry Part B: Clinical Cytometry focuses on the development and applications of cellular system analysis and array based technologies as applied to clinical practice and translational research. This journal also covers relevant techniques such as flow cytometry, image cytometry, beadbased and slide-based array analyses, as well as other cell-based spectroscopic analyses. In addition, Clinical Cytometry publishes clinical and translational investigations that identify and validate the features and molecules important in diagnosis, prognosis, and therapeutic management of patients
GLV-1h68 vaccinia virus therapy of neuroendocrine neoplasms
2020-05-29

Abstract Background: Oncolytic virotherapy is an upcoming treatment option for many tumor entities. But so far, a first oncolytic virus only was approved for advanced stages of malignant melanomas. Neuroendocrine tumors (NETs) constitute a heterogenous group of tumors arising from the neuroendocrine system at diverse anatomic sites. Due to often slow growth rates and (in most cases) endocrine non-functionality, NETs are often detected only in a progressed metastatic situation, where therapy options are still severely limited. So far, immunotherapies and especially immunovirotherapies are not established as novel treatment modalities for NETs. Methods: In this immunovirotherapy study, pancreatic NET (BON-1, QGP-1), lung NET (H727, UMC-11), as well as neuroendocrine carcinoma (NEC) cell lines (HROC-57, NEC-DUE1) were employed. The well characterized genetically engineered vaccinia virus GLV-1h68, which has already been investigated in various clinical trials, was chosen as virotherapeutical treatment modality. Results: Profound oncolytic efficiencies were found for NET/NEC tumor cells. Besides, NET/NEC tumor cell bound expression of GLV-1h68-encoded marker genes was observed also. Furthermore, a highly efficient production of viral progenies was detected by sequential virus quantifications. Moreover, the mTOR inhibitor everolimus, licensed for treatment of metastatic NETs, was not found to interfere with GLV-1h68 replication, making a combinatorial treatment of both feasible. Conclusions: In summary, the oncolytic vaccinia virus GLV-1h68 was found to exhibit promising antitumoral activities, replication capacities and a potential for future combinatorial approaches. This has been shown in a widespread spectrum of cancers in a preclinical setting and now has to be further evaluated for treatment of metastatic neuroendocrine cancer.
The Impact of an Audience Response System on a summative Assessment, a controlled Field Study
2020-05-29

Abstract Background Audience response systems allow to activate the audience and to receive a direct feedback of participants during lectures. Modern systems do not require any proprietary hardware anymore. Students can directly respond on their smartphone. Several studies reported about a high level of satisfaction of students when audience response systems are used, however their impact on learning success is still unclear. Methods In order to evaluate the impact of an audience response system on the learning success we implemented the audience response system eduVote into a seminar series and performed a controlled crossover study on its impact on assessments. 154 students in nine groups were taught the same content. In four groups, eduVote was integrated for the first topic while five groups were taught this topic without the audience response systems. For a second topic, the groups were switched: Those groups who were taught before using eduVote were now taught without the audience response system and vice versa. We then analysed the impact of the audience response system on the students’ performance in a summative assessment and specifically focused on questions dealing with the topic, for which the audience response system was used during teaching. We further assessed the students’ perception on the use of eduVote using questionnaires. Results In our controlled crossover study we could not confirm an impact of the audience response system eduVote on long-term persistence i.e. the students’ performance in the summative assessment. Our evaluation revealed that students assessed the use of eduVote very positively, felt stronger engaged and better motivated to deal with the respective topics and would prefer their integration into additional courses as well. In particular we identified that students who feel uncomfortable with answering questions in front of others profit from the use of an audience response system during teaching. Conclusions Audience response systems motivate and activate students and increase their engagement during classes. However, their impact on long-term persistence and summative assessments may be limited. Audience response systems, however, specifically allow activating students which cannot be reached by the traditional way of asking questions without such an anonymous tool.
Characterization of Recessive Parkinson Disease in a Large Multicenter Study
2020-05-30

Studies of the phenotype and population distribution of rare genetic forms of parkinsonism are required, now that gene‐targeting approaches for Parkinson disease have reached the clinical trial stage. We evaluated the frequencies of PRKN , PINK1 , and DJ‐1 mutations in a cohort of 1,587 cases. Mutations were found in 14.1% of patients; 27.6% were familial and 8% were isolated. PRKN was the gene most frequently mutated in Caucasians, whereas PINK1 mutations predominated in Arab‐Berber individuals. Patients with PRKN mutations had an earlier age at onset, and less asymmetry, levodopa‐induced motor complications, dysautonomia, and dementia than those without mutations. ANN NEUROL 2020;88:843–850
Genomewide Association Study of Platelet Reactivity and Cardiovascular Response in Patients Treated With Clopidogrel: A Study by the International Clopidogrel Pharmacogenomics Consortium
2020-05-30

Antiplatelet response to clopidogrel shows wide variation, and poor response is correlated with adverse clinical outcomes. CYP2C19 loss‐of‐function alleles play an important role in this response, but account for only a small proportion of variability in response to clopidogrel. An aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify other genetic determinants of clopidogrel pharmacodynamics and clinical response. A genomewide association study (GWAS) was performed using DNA from 2,750 European ancestry individuals, using adenosine diphosphate‐induced platelet reactivity and major cardiovascular and cerebrovascular events as outcome parameters. GWAS for platelet reactivity revealed a strong signal for CYP2C19*2 ( P value = 1.67e−33). After correction for CYP2C19*2 no other single‐nucleotide polymorphism reached genomewide significance. GWAS for a combined clinical end point of cardiovascular death, myocardial infarction, or stroke (5.0% event rate), or a combined end point of cardiovascular death or myocardial infarction (4.7% event rate) showed no significant results, although in coronary artery disease, percutaneous coronary intervention, and acute coronary syndrome subgroups, mutations in SCOS5P1 , CDC42BPA , and CTRAC1 showed genomewide significance (lowest P values: 1.07e−09, 4.53e−08, and 2.60e−10, respectively). CYP2C19*2 is the strongest genetic determinant of on‐clopidogrel platelet reactivity. We identified three novel associations in clinical outcome subgroups, suggestive for each of these outcomes.
Illuminating Subsurface Microbial Water Quality Patterns Using Adenosine Triphosphate and Dynamic Time Warping Approaches
2020-05-30

Abstract Aquifer microbial water quality evaluations are often performed by collecting groundwater samples from monitoring wells. While samples collected from continuously pumped sources are seldom disputed as representative of the aquifer, natural biofilm present in the vicinity of well screens may introduce unwanted microbial artefacts in monitoring wells that are only periodically sampled. The need for well water purging to obtain samples void of these artefacts has been widely recognized. However, purging methods are not standardized; many approaches presume that physico‐chemical water quality stability achieved through the removal of 3 to 5 well volumes is indicative of the stability of target analytes. Using a data set collected from a shallow unconfined aquifer in Southern Ontario, Canada, the need for using dedicated approaches that account for the time‐dependent nature of microbial water quality changes was demonstrated. Specifically, the utility of adenosine triphosphate (ATP) as a rapid, field‐ready biochemical indicator of microbial water quality stability was investigated. This work shows that ATP concentrations reflect time‐limited (bio)colloid transport processes that are consistent with other microbial water quality parameters monitored, but different from commonly measured physical and chemical water quality indicators of well purging adequacy. ATP concentrations occasionally fluctuated even after 3 or 4 h of purging, indicating that microbial artefacts attributable to biofilms in the vicinity of the well screen can still persist. The recurrence of characteristic ATP patterns in each well was systematically examined through the novel application of dynamic time warping (DTW), a nonparametric time series analysis approach. These patterns are believed to be linked with seasonal hydrogeological conditions, which warrant consideration in the design and interpretation of subsurface microbial water quality investigations.
Can’t decide how much to EAT? Effort variability for reward is associated with cognitive restraint
2020-05-31

Abstract Food intake is inherently variable and often characterized by episodical restraint or overeating (uncontrolled eating). Such heightened variability in intake has been associated with higher variability in the brain response to food reward, but it is an open issue whether comparable associations with elevated variability in reward seeking exist. Here, we assessed whether restraint and uncontrolled eating as markers of trait-like variability in eating are associated with higher intra-individual variability in reward seeking as captured by a cost-benefit paradigm. To test this hypothesis, 81 healthy, overnight-fasting participants ( M BMI = 23.0 kg/m 2 ± 2.95) completed an effort allocation task (EAT) twice. In the EAT, participants had to exert physical effort to earn monetary and food rewards and indicated levels of wanting through visual analog scales (VAS). As predicted, we found that greater trial-by-trial effort variability was associated with lower scores on cognitive restraint, r p (78) = −.28, p = .011 (controlled for average effort). In line with previous findings, higher wanting variability was associated with higher BMI, r p (78) = .25, p = .026 (controlled for average effort). Collectively, our results support the idea that higher variability in reward seeking is a potential risk factor for eating beyond homeostatic need. Since associations with variability measures of reward exceeded associations with average reward seeking, our findings may indicate that variability in the representation of the reward value could be a crucial aspect driving fluctuations in food intake.