julilili42/papers huggingface dataset:
Meta-analysis of fish early life stage tests—Association of toxic ratios and acute-to-chronic ratios with modes of action
2018-01-19

Abstract Fish early life stage (ELS) tests (Organisation for Economic Co-operation and Development test guideline 210) are widely conducted to estimate chronic fish toxicity. In these tests, fish are exposed from the embryonic to the juvenile life stages. To analyze whether certain modes of action are related to high toxic ratios (i.e., ratios between baseline toxicity and experimental effect) and/or acute-to-chronic ratios (ACRs) in the fish ELS test, effect concentrations (ECs) for 183 compounds were extracted from the US Environmental Protection Agency's ecotoxicity database. Analysis of ECs of narcotic compounds indicated that baseline toxicity could be observed in the fish ELS test at similar concentrations as in the acute fish toxicity test. All nonnarcotic modes of action were associated with higher toxic ratios, with median values ranging from 4 to 9.3 × 104 (uncoupling &amp;lt; reactivity &amp;lt; neuromuscular toxicity &amp;lt; methemoglobin formation &amp;lt; endocrine disruption &amp;lt; extracellular matrix formation inhibition). Four modes of action were also found to be associated with high ACRs: 1) lysyl oxidase inhibition leading to notochord distortion, 2) putative methemoglobin formation or hemolytic anemia, 3) endocrine disruption, and 4) compounds with neuromuscular toxicity. For the prediction of ECs in the fish ELS test with alternative test systems, endpoints targeted to the modes of action of compounds with enhanced toxic ratios or ACRs could be used to trigger fish ELS tests or even replace these tests. Environ Toxicol Chem 2018;37:955–969. © 2018 SETAC Abstract Modes of action in the fish early life stage test that lead to median toxic ratios and acute-to-chronic ratios (ACRs) ≥10. The ACR was calculated using acute toxicity in juvenile/adult fish (AFT) or zebrafish embryos (ZFET) as reference values.
The retinal locus of fixation in simulations of progressing central scotomas
2018-01-19

Patients with central scotoma use a preferred retinal locus (PRL) of fixation to perform visual tasks. Some of the conditions that cause central scotoma are progressive, and as a consequence, the PRL needs to be adjusted throughout the progression. The present study investigates the peripheral locus of fixation in subjects under a simulation of progressive central scotoma. Five normally sighted subjects participated in the study. A foveally centered mask of varying size was presented to simulate the scotoma. Initially, subjects developed a peripheral locus of fixation under simulation of a 6° scotoma, which was used as a baseline. The progression was simulated in two separate conditions: a gradual progression and an abrupt progression. In the gradual progression, the diameter of the scotoma increased by a fixed amount of either 1° or 2° of visual angle, thus scotomas of 8°, 10°, and 11° of visual angle were simulated. In the abrupt progression, the diameter was adjusted individually to span the area of the visual field used by the current peripheral locus of fixation. Subjects located the peripheral locus of fixation along the same meridian under simulation of scotoma progression. Furthermore, no differences between the fixation stability of the baseline locus of fixation and the incremental progression locus of fixation were found whereas, in abrupt progression, the fixation stability decreased significantly. These results provide first insight into fixation behavior in a progressive scotoma and may contribute to the development of training tools for patients with progressive central maculopathies.
Homonymous Hemianopia in Children and Adolescents: An MRI Study
2018-01-19

Aim Diagnosing homonymous hemianopia (HH) in children can be difficult due to inability to comply with perimetry. Therefore, HH can often only be suspected by magnetic resonance imaging (MRI) showing lesions to the retrochiasmatic visual pathways. The aim of our retrospective observational cross-sectional study was to improve the radiologic detection of HH. Methods MRIs of 21 subjects (5–17 years old) with ophthalmologically confirmed HH (14 complete, 7 incomplete hemianopias) were analyzed. In addition, we asked four questions looking at everyday problems possibly related to the HH. The questions asked for (1) problems in avoiding objects/people, (2) bumping into objects/people, (3) difficulties in judging stairs, and (4) difficulties in grasping objects. Results We found neuroanatomical correlates of the HH in all 21 participants, with the optic radiation being involved in almost all participants (20/21). Everyday problems possibly related to the HH were reported for all nine patients with postneonatally acquired complete hemianopias. In contrast, no such problems were reported for seven patients with incomplete HH (7/7) and for 3/5 patients with complete hemianopias due to pre-, peri- or neonatally acquired brain lesions. Interpretation A dedicated radiologic analysis of the retrochiasmatic optic pathway should routinely be performed in children with brain lesions to identify children with HH. Early onset and incomplete HH are predictors for successful compensation.
Autofocusing‐based phase correction
2018-01-19

Purpose Phase artifacts due to B 0 inhomogeneity can severely degrade the quality of MR images. The artifacts are particularly prominent in long‐TE scans and usually appear as ghosting and blur. We propose a retrospective phase correction method based on autofocusing. The proposed method uses raw data acquired with standard imaging sequences, and does not rely on navigators or external measures of field inhomogeneity. Methods We formulate and solve the optimization problem, where we seek the latent phase offsets that are associated with an optimal value of the image quality measure that is evaluated in the spatial domain. As a quality measure we use entropy computed on spatial image gradients. We propose two types of objective function, both compatible with parallel imaging and accelerated image acquisition. Results We evaluate the method on both synthetic and real data. In real data case we evaluate the performance on a range of sequences and images acquired with different acceleration factors. The experimental results demonstrate that our method is capable of minimizing ghosting artifacts and that the quality of the output images is similar to navigator‐based reconstructions. Conclusion The presented technique can be alternative to or complement navigator‐based methods, and is able to improve images with severe phase artifacts from all standard imaging sequences. Magn Reson Med 80:958–968, 2018. © 2018 International Society for Magnetic Resonance in Medicine.
Schelling’s prehistory in Russia: the legacy of enlightenment
2018-01-19

Schelling’s first Russian disciple, D.M. Vellanskij, met his teacher at Würzburg in 1803. It was the heyday of Schelling’s philosophy of identity, the identity of spirit and nature, of mind and matter. Yet, teacher and student differ on the labels they applied to this philosophy. Vellanskij thought of it as the peak of human ‘Aufklärung’, whereas Schelling abhorred the term due to controversies going on within German philosophy at the time (‘Berliner Aufklärung’). The argument put forward here is that Vellanskij was right in using the term ‘Enlightenment’ for Schelling’s philosophy of identity, which conceptualized – via nature – the ideas of free movement, tolerance and human solidarity.
Phytotoxin produced by the netted scab pathogen, Streptomyces turgidiscabies strain 65, isolated in Sweden
2018-01-20

Streptomyces spp. are a highly diverse group of bacteria most of which are soil-inhabiting saprophytes. A few are plant pathogens that produce a family of phytotoxins called thaxtomins and cause significant economic losses, e.g., by reducing the marketability of potato tubers (Solanum tuberosum). In northern Europe, S. scabies, S. turgidiscabies and S. europaeiscabiei are the most common plant pathogenic species. In this study, a Streptomyces strain isolated from a netted scab lesion on a tuber of potato cv. Bintje in northern Sweden was identified as S. turgidiscabies but was found to differ in the genomic region carrying genes required for thaxtomin biosynthesis. Our results showed that the strain did not produce thaxtomin but rather phytotoxin fridamycin E, which is an anthraquinone novel to plant pathogenic Streptomyces spp. Fridamycin E was shown to reduce or inhibit sprouting of potato microtubers in vitro. While fridamycin E is known to have antibiotic activity against Gram-positive bacteria, the inhibitory activity of fridamycin E on plant growth is a novel finding.
A Diverse and Versatile Regiospecific Synthesis of Tetrasubstituted Alkylsulfanylimidazoles as p38α Mitogen-Activated Protein Kinase Inhibitors
2018-01-20

An alternative strategy for the synthesis of 1-aryl- and 1-alkyl-2-methylsulfanyl-4-(4-fluorophenyl)-5-(pyridin-4-yl)imidazoles as potential p38α mitogen-activated protein kinase inhibitors is reported. The regioselective N-substitution of the imidazole ring was achieved by treatment of α-aminoketones with different aryl or alkyl isothiocyanates. In contrast to previously published synthesis routes starting from 2-amino-4-methylpyridine, the presented route is characterized by a higher flexibility and a lower number of steps. This strategy was also applied to access 1-alkyl-2-methylsulfanyl-5-(4-fluorophenyl)-4-(pyridin-4-yl)imidazoles in six steps starting from 2-chloro-4-methylpyridine.
Chondrosarcoma: A Rare Misfortune in Aging Human Cartilage? The Role of Stem and Progenitor Cells in Proliferation, Malignant Degeneration and Therapeutic Resistance
2018-01-21

Unlike other malignant bone tumors including osteosarcomas and Ewing sarcomas with a peak incidence in adolescents and young adults, conventional and dedifferentiated chondrosarcomas mainly affect people in the 4th to 7th decade of life. To date, the cell type of chondrosarcoma origin is not clearly defined. However, it seems that mesenchymal stem and progenitor cells (MSPC) in the bone marrow facing a pro-proliferative as well as predominantly chondrogenic differentiation milieu, as is implicated in early stage osteoarthritis (OA) at that age, are the source of chondrosarcoma genesis. But how can MSPC become malignant? Indeed, only one person in 1,000,000 will develop a chondrosarcoma, whereas the incidence of OA is a thousandfold higher. This means a rare coincidence of factors allowing escape from senescence and apoptosis together with induction of angiogenesis and migration is needed to generate a chondrosarcoma. At early stages, chondrosarcomas are still assumed to be an intermediate type of tumor which rarely metastasizes. Unfortunately, advanced stages show a pronounced resistance both against chemo- and radiation-therapy and frequently metastasize. In this review, we elucidate signaling pathways involved in the genesis and therapeutic resistance of chondrosarcomas with a focus on MSPC compared to signaling in articular cartilage (AC).
Intracellular Ca 2+ stores control in vivo neuronal hyperactivity in a mouse model of Alzheimer’s disease
2018-01-22

Significance Although both patients with Alzheimer’s disease (AD) and mouse models of the disease suffer from a profound neuronal hyperactivity mediating an impairment of memory and cognition, the underlying mechanisms remain elusive. Here, we show that neuronal hyperactivity is a hallmark of healthy aging but is further aggravated by AD-related mutations in presenilin 1 protein. AD-mediated enhancement of neuronal hyperactivity occurred even in the absence of amyloid plaques and neuroinflammation, mainly due to a presenilin-mediated dysfunction of intracellular Ca 2+ stores in presynaptic boutons, likely causing more frequent activation of synaptic NMDA receptors. Emptying the stores normalized neuronal network activity in mutant mice, thus identifying presynaptic Ca 2+ stores as a key element controlling AD-related neuronal hyperactivity and as a target for disease-modifying treatments.
Students’ idiosyncratic perceptions of teaching quality in mathematics: A result of rater tendency alone or an expression of dyadic effects between students and teachers?
2018-01-22

Student ratings of teaching quality have been shown to be powerful predictors of important academic outcome variables. This is the case despite the fact that students from the same classroom can perceive teaching quality quite differently in their own idiosyncratic ways. These differences among students in the same classroom are typically dismissed as the result of individual rating tendencies (e.g., rater leniency) with only low relevance for students’ learning. However, such idiosyncratic perceptions might also be the result of meaningful differences among students in that they could reflect dyadic effects between individual students and specific teachers (e.g., a trusting relationship). In the present study, we examined students’ perceptions of teaching quality in mathematics lessons (structure, monitoring, comprehensibility, and support) in a nationally representative sample of 204 German secondary school mathematics classes. We used a quasi-experimental design for students who had the same teacher in Grades 9 and 10 and students who had a new teacher in Grade 10 to differentiate between students’ time-consistent rating tendencies and dyadic student-teacher effects. The results of latent variable models showed that student rating tendencies were found for all quality dimensions, with the highest impact observed for students’ general impression and teacher monitoring. The results for students with the same teacher showed additional dyadic effects. Students’ general impression and comprehensibility exhibited greater time consistency when students rated the same teacher than when students rated different teachers. Finally, students’ rating tendencies and dyadic effects were related to students’ outcomes. (PsycINFO Database Record (c) 2018 APA, all rights reserved)
Evaluating the impact of fast-fMRI on dynamic functional connectivity in an event-based paradigm
2018-01-22

The human brain is known to contain several functional networks that interact dynamically. Therefore, it is desirable to analyze the temporal features of these networks by dynamic functional connectivity (dFC). A sliding window approach was used in an event-related fMRI (visual stimulation using checkerboards) to assess the impact of repetition time (TR) and window size on the temporal features of BOLD dFC. In addition, we also examined the spatial distribution of dFC and tested the feasibility of this approach for the analysis of interictal epileptiforme discharges. 15 healthy controls (visual stimulation paradigm) and three patients with epilepsy (EEG-fMRI) were measured with EPI-fMRI. We calculated the functional connectivity degree (FCD) by determining the total number of connections of a given voxel above a predefined threshold based on Pearson correlation. FCD could capture hemodynamic changes relative to stimulus onset in controls. A significant effect of TR and window size was observed on FCD estimates. At a conventional TR of 2.6 s, FCD values were marginal compared to FCD values using sub-seconds TRs achievable with multiband (MB) fMRI. Concerning window sizes, a specific maximum of FCD values (inverted u-shape behavior) was found for each TR, indicating a limit to the possible gain in FCD for increasing window size. In patients, a dynamic FCD change was found relative to the onset of epileptiform EEG patterns, which was compatible with their clinical semiology. Our findings indicate that dynamic FCD transients are better detectable with sub-second TR than conventional TR. This approach was capable of capturing neuronal connectivity across various regions of the brain, indicating a potential to study the temporal characteristics of interictal epileptiform discharges and seizures in epilepsy patients or other brain diseases with brief events.
Ciliary and rhabdomeric photoreceptor-cell circuits form a spectral depth gauge in marine zooplankton
2018-01-22

Abstract Ciliary and rhabdomeric photoreceptor cells represent two main lines of photoreceptor evolution in animals. The two photoreceptor-cell types coexist in some animals, however how they functionally integrate is unknown. We used connectomics to map synaptic paths between ciliary and rhabdomeric photoreceptors in the planktonic larva of the annelid Platynereis and found that ciliary photoreceptors are presynaptic to the rhabdomeric circuit. The behaviors mediated by the ciliary and rhabdomeric cells also interact hierarchically. The ciliary photoreceptors are UV-sensitive and mediate downward swimming to non-directional UV light, a behavior absent in ciliary-opsin knockouts. UV avoidance antagonizes positive phototaxis mediated by the rhabdomeric eyes so that vertical swimming direction is determined by the ratio of blue/UV light. Since this ratio increases with depth, Platynereis larvae may use it as a depth gauge during planktonic migration. Our results revealed a functional integration of ciliary and rhabdomeric photoreceptors with implications for eye and photoreceptor evolution.
Abstract TMP48: Subcortical Volumes Associated With Post-Stroke Motor Performance Vary Across Impairment Severity, Time Since Stroke, and Lesion Laterality: an ENIGMA Stroke Recovery Analysis
2018-01-22

Associations between subcortical gray matter volume and motor performance post-stroke are unclear, partly because many stroke MRI studies are underpowered. Potential influences of the severity of motor impairment, lesion laterality, and time since stroke on these associations is also unknown. Here, we addressed these questions using a large dataset (n=629) from the ENIGMA Stroke Recovery working group (http://enigma.usc.edu). Regression analyses examined brain volumes as predictors of motor scores. ENIGMA FreeSurfer protocols extracted volumes from 16 subcortical regions on T1-weighted MRIs; segmentations were manually quality controlled. Motor scores were calculated as a percentage of the maximum possible score (100% = no impairment). Covariates (e.g., age, sex, intracranial volume) were modeled. Statistical significance was assessed nonparametrically by permutation. Separate analyses were performed, stratifying by motor severity and time since stroke. Each analysis was also subdivided by lesioned hemisphere. The motor severity analysis (Table 1A) used subgroups of mild (66.7-99.9%), moderate (33.3-66.6%), and severe (0-33.2%). Significant associations were found for mild and moderate, but not severe, stroke; only the left hemisphere stroke group showed further significant results. The time since stroke analysis (Table 1B) used subgroups of acute (&lt;1 month), subacute (1-6 months), and chronic (&gt;6 months). Significant associations were found in chronic stroke, but not acute, subacute. Left versus right hemisphere lesions generated different results in chronic stroke. Overall, these results show that the most significant associations between subcortical volumes and motor outcomes are in chronic mild-to-moderate stroke. Stroke subgroups may recover via disparate mechanisms; establishing biomarkers of impairment and disability across stroke subgroups may be useful for clinical trials.
Detecting non-functional circuit activity in SoC designs
2018-01-22

In this paper, we present a methodology for the automatic detection of non-functional circuit activity in SoC designs. Our methodology formally analyses an RTL design, generates an internal graph representation and traverses the graph using given simulation traces. We evaluate an open source processor with a given set of benchmark applications using our approach. With a commercial RTL simulator, we observe an average register toggle activity of 6.7% -- 11.5%, but our experiments show that 86.1 -- 92.7% of these toggles are non-functional, i.e. not necessary for producing the exact same circuit output. We further evaluate the efficiency of the clock gating architecture of a commercial ASIP. For the Dhrystone benchmark we show that, even though only 34.7% of the registers are clocked on average, still 64.3% of the non-clock-gated registers in this ASIP are not needed on average to produce exactly the same circuit output.
Abstract TMP15: Penumbral Rescue by Normobaric O2 in Ischemic Stroke With Target Mismatch ProFile (PROOF)
2018-01-22

Introduction/Hypothesis: Despite effective reperfusion therapies, outcome following ischemic stroke (IS) often remains poor. Shortly after IS onset, the already necrotic area is surrounded by the severely hypoperfused but still viable penumbra. Sustaining the latter may widen treatment time windows and improve outcomes. As tissue damage in IS is primarily mediated by hypoxia, increasing penumbral oxygen (O2) supply seems a logical approach. Normobaric hyperoxygenation (NBHO) increased penumbral O2 and attenuated brain injury when initiated early in animal models of transient vessel occlusion. The few clinical trials conducted so far did not adapt these insights: NBHO initiation was late (treatment windows of more than 9 hours) and patients eligible for intravenous thrombolysis and endovascular treatment were excluded. Methods: Multi-center, randomized phase-II proof-of-concept trial studying NBHO adjunct to standard IS treatment; adaptive patient sample size of 180 to 460 depending on interim analysis. Eligibility: Patients with an acute large vessel occlusion in the anterior circulation (terminal ICA plus M1, proximal M1, or distal M1) and an Alberta Stroke Program Early CT Score of 7 or higher. Study treatment must be initiated prior to recanalization therapy and within 3 hours after IS onset. NBHO is achieved by administration of high-flow O2 (40 L/min) via non-rebreather face mask with reservoir or FiO2 of 1.0 during mechanical ventilation. NBHO will be stopped after endovascular treatment or applied for a maximum of four hours in case of not-attempted endovascular treatment. Controls will receive standard O2 supplementation whenever required. Primary Endpoint: Infarct growth from baseline to 24 hours; key secondary endpoint: Δ24h-NIHSS. Conclusion: PROOF is the first clinical trial to incorporate two cornerstones of effective experimental NBHO: early initiation and fast reperfusion. If proven beneficial, phase-III trials may be undertaken. Considering its low cost, NBHO may impact stroke care worldwide.