julilili42/papers huggingface dataset:
Cereblon-binding proteins expression levels correlate with hyperdiploidy in newly diagnosed multiple myeloma patients
2019-01-29

Abstract Immunomodulatory drugs (IMIDs) are very effective in the treatment of multiple myeloma (MM). The description of their cereblon-mediated mechanism of action was a hallmark in MM research. Although the importance of IMID-induced degradation of cereblon-binding proteins is well described in vitro, the prognostic value of their expression levels in MM cells is less clear. Based on recently published data showing somewhat conflicting RNA levels, we analyzed the association between the levels of the Ikaros family zinc finger protein 1 (IKZF1), IKZF3, and karyopherin subunit alpha 2 (KPNA2) proteins measured by flow cytometry and prognostic parameters in 214 newly diagnosed MM patients who were randomized in the GMMG HD6 trial. No statistically significant associations between the expression levels and age, gender, light chain type, International Staging System (ISS) stage or cytogenetic high- and normal risk groups could be identified. Hyperdiploid MM cells expressed significantly higher levels of IKZF1, IKZF3 and KPNA2 than nonhyperdiploid cells. In contrast, translocation t(11;14) was associated with significantly lower expression levels. In conclusion, the observed overexpression of cereblon-binding proteins in MM cells with gain of chromosomes 5, 9, 11, 15, and 19 is consistent with the previously proposed positive regulation of MYC by IKZF1 and IKZF3, as well as MYC activation in hyperdiploid MM cells.
Interface properties of CoPc and CoPcF16 on graphene/nickel: influence of germanium intercalation
2019-01-29

Photoelectron spectroscopy was used to investigate electronic interface properties and interactions of the organic semiconductors CoPc and CoPcF<sub>16</sub> on graphene/nickel based substrates. Additional focus was put on the influence of germanium intercalation of graphene/nickel. The presented results demonstrate that germanium can decouple graphene from nickel and in this manner restore its buffer layer properties. No charge transfer from the substrate to the organic layer is observed in the germanium intercalated case, while interface related peaks in the Co 2p core level spectra indicate such charge transfer on graphene/nickel. Strong interface dipoles are found for CoPcF<sub>16</sub> on graphene/nickel and on germanium intercalated graphene/nickel. Fluorine Auger parameters have been measured, and the results provide evidence for polarization and charge transfer screening effects of different amounts at the unlike film-substrate interfaces. The various contributions to the observed shifts are discussed.
Association of Online Learning Behavior and Learning Outcomes for Medical Students: Large-Scale Usage Data Analysis (Preprint)
2019-01-29

<sec> <title>BACKGROUND</title> Digital learning environments have become very common in the training of medical professionals, and students often use such platforms for exam preparation. Multiple choice questions (MCQs) are a common format in medical exams and are used by students to prepare for said exams. </sec> <sec> <title>OBJECTIVE</title> We aimed to examine whether particular learning activities contributed more strongly than others to users’ exam performance. </sec> <sec> <title>METHODS</title> We analyzed data from users of an online platform that provides learning materials for medical students in preparation for their final exams. We analyzed whether the number of learning cards viewed and the number of MCQs taken were positively related to learning outcomes. We also examined whether viewing learning cards or answering MCQs was more effective. Finally, we tested whether taking individual notes predicted learning outcomes, and whether taking notes had an effect after controlling for the effects of learning cards and MCQs. Our analyses from the online platform Amboss are based on user activity data, which supplied the number of learning cards studied and test questions answered. We also included the number of notes from each of those 23,633 users who had studied at least 200 learning cards and had answered at least 1000 test exam questions in the 180 days before their state exam. The activity data for this analysis was collected retrospectively, using Amboss archival usage data from April 2014 to April 2017. Learning outcomes were measured using the final state exam scores that were calculated by using the answers voluntarily entered by the participants. </sec> <sec> <title>RESULTS</title> We found correlations between the number of cards studied (r=.22; P&lt;.001) and the number of test questions that had been answered (r=.23; P&lt;.001) with the percentage of correct answers in the learners’ medical exams. The number of test questions answered still yielded a significant effect, even after controlling for the number of learning cards studied using a hierarchical regression analysis (β=.14; P&lt;.001; ΔR2=.017; P&lt;.001). We found a negative interaction between the number of learning cards and MCQs, indicating that users with high scores for learning cards and MCQs had the highest exam scores. Those 8040 participants who had taken at least one note had a higher percentage of correct answers (80.94%; SD=7.44) than those who had not taken any notes (78.73%; SD=7.80; t23631=20.95; P&lt;.001). In a stepwise regression, the number of notes the participants had taken predicted the percentage of correct answers over and above the effect of the number of learning cards studied and of the number of test questions entered in step one (β=.06; P&lt;.001; ΔR2=.004; P&lt;.001). </sec> <sec> <title>CONCLUSIONS</title> These results show that online learning platforms are particularly helpful whenever learners engage in active elaboration in learning material, such as by answering MCQs or taking notes. </sec>
Exploration of New Contrasts, Targets, and MR Imaging and Spectroscopy Techniques for Neuromuscular Disease – A Workshop Report of Working Group 3 of the Biomedicine and Molecular Biosciences COST Action BM1304 MYO-MRI
2019-01-30

Neuromuscular diseases are characterized by progressive muscle degeneration and muscle weakness resulting in functional disabilities. While each of these diseases is individually rare, they are common as a group, and a large majority lacks effective treatment with fully market approved drugs. Magnetic resonance imaging and spectroscopy techniques (MRI and MRS) are showing increasing promise as an outcome measure in clinical trials for these diseases. In 2013, the European Union funded the COST (co-operation in science and technology) action BM1304 called MYO-MRI (www.myo-mri.eu), with the overall aim to advance novel MRI and MRS techniques for both diagnosis and quantitative monitoring of neuromuscular diseases through sharing of expertise and data, joint development of protocols, opportunities for young researchers and creation of an online atlas of muscle MRI and MRS. In this report, the topics that were discussed in the framework of working group 3, which had the objective to: Explore new contrasts, new targets and new imaging techniques for NMD are described. The report is written by the scientists who attended the meetings and presented their data. An overview is given on the different contrasts that MRI can generate and their application, clinical needs and desired readouts, and emerging methods.
Healthy Brain Aging Modifies Microglial Calcium Signaling In Vivo
2019-01-30

Brain aging is characterized by a chronic, low-grade inflammatory state, promoting deficits in cognition and the development of age-related neurodegenerative diseases. Malfunction of microglia, the brain-resident immune cells, was suggested to play a critical role in neuroinflammation, but the mechanisms underlying this malfunctional phenotype remain unclear. Specifically, the age-related changes in microglial Ca2+ signaling, known to be linked to its executive functions, are not well understood. Here, using in vivo two-photon imaging, we characterize intracellular Ca2+ signaling and process extension of cortical microglia in young adult (2–4-month-old), middle-aged (9–11-month-old), and old (18–21-month-old) mice. Our data revealed a complex and nonlinear dependency of the properties of intracellular Ca2+ signals on an animal’s age. While the fraction of cells displaying spontaneous Ca2+ transients progressively increased with age, the frequencies and durations of the spontaneous Ca2+ transients followed a bell-shaped relationship, with the most frequent and largest Ca2+ transients seen in middle-aged mice. Moreover, in old mice microglial processes extending toward an ATP source moved faster but in a more disorganized manner, compared to young adult mice. Altogether, these findings identify two distinct phenotypes of aging microglia: a reactive phenotype, abundantly present in middle-aged animals, and a dysfunctional/senescent phenotype ubiquitous in old mice.
Scientific Reasoning in Elementary School Children: Assessment of the Inquiry Cycle
2019-01-30

Scientific reasoning abilities are already developing in elementary-school-aged children and enable them to understand the world around them. The goal of the current study was to develop a new instrument for 8- to 10-year-old children in Grades 3 and 4 to measure their understanding of the steps of the scientific inquiry cycle (SIC). Such an understanding is essential for scientific reasoning as well as for inquiry-based learning approaches and, above all, for scientific practice. We developed and applied 15 items in a sample of 878 third- and fourth-grade students ( n = 434, Grade 3; n = 435, Grade 4). As confirmed by item response theory (IRT) modeling, the items produced reliable scale scores. Furthermore, we explored the relations between children’s SIC performances, cognitive abilities, and epistemic beliefs. As expected, intelligence, text comprehension, experimentation strategies, and sophisticated epistemic beliefs were positively associated with children’s SIC performance, a finding that helps to establish initial evidence for the construct validity of the SIC test scores.
Doxapram stimulates respiratory activity through distinct activation of neurons in the nucleus hypoglossus and the pre-Bötzinger complex
2019-01-30

Doxapram is a respiratory stimulant used for decades as a treatment option in apnea of prematurity refractory to methylxanthine treatment. Its mode of action, however, is still poorly understood. We investigated direct effects of doxapram on the pre-Bötzinger complex (PreBötC) and on a downstream motor output system, the hypoglossal nucleus (XII), in the transverse brainstem slice preparation. While doxapram has only a modest stimulatory effect on frequency of activity generated within the PreBötC, a much more robust increase in the amplitude of population activity in the subsequent motor output generated in the XII was observed. In whole cell patch-clamp recordings of PreBötC and XII neurons, we confirmed significantly increased firing of evoked action potentials in XII neurons in the presence of doxapram, while PreBötC neurons showed no significant alteration in firing properties. Interestingly, the amplitude of activity in the motor output was not increased in the presence of doxapram compared with control conditions during hypoxia. We conclude that part of the stimulatory effects of doxapram is caused by direct input on brainstem centers with differential effects on the rhythm generating kernel (PreBötC) and the downstream motor output (XII). NEW &amp; NOTEWORTHY The clinically used respiratory stimulant doxapram has distinct effects on the rhythm generating kernel (pre-Bötzinger complex) and motor output centers (nucleus hypoglossus). These effects are obliterated during hypoxia and are mediated by distinct changes in the intrinsic properties of neurons of the nucleus hypoglossus and synaptic transmission received by pre-Bötzinger complex neurons.
Complex charges, time reversal asymmetry, and interior-boundary conditions in quantum field theory
2019-01-30

While fundamental physically realistic Hamiltonians should be invariant under time reversal, time asymmetric Hamiltonians can occur as mathematical possibilities or effective Hamiltonians. Here, we study conditions under which non-relativistic Hamiltonians involving particle creation and annihilation, as come up in quantum field theory (QFT), are time asymmetric. It turns out that the time reversal operator T can be more complicated than just complex conjugation, which leads to the question which criteria determine the correct action of time reversal. We use Bohmian trajectories for this purpose and show that time reversal symmetry can be broken when charges are permitted to be complex numbers, where `charge' means the coupling constant in a QFT that governs the strength with which a fermion emits and absorbs bosons. We pay particular attention to the technique for defining Hamiltonians with particle creation based on interior-boundary conditions, and we find them to generically be time asymmetric. Specifically, we show that time asymmetry for complex charges occurs whenever not all charges have equal or opposite phase. We further show that, in this case, the corresponding ground states can have non-zero probability currents, and we determine the effective potential between fermions of complex charge.
Stimulation of the vagus nerve reduces learning in a go/no-go reinforcement learning task
2019-01-30

Abstract When facing decisions to approach rewards or to avoid punishments, we often figuratively go with our gut, and the impact of metabolic states such as hunger on motivation are well documented. However, whether and how vagal feedback signals from the gut influence instrumental actions is unknown. Here, we investigated the effect of non-invasive transcutaneous vagus nerve stimulation (tVNS) vs. sham (randomized cross-over design) on approach and avoidance behavior using an established go/no-go reinforcement learning paradigm (Guitart-Masip et al., 2012) in 39 healthy, participants after an overnight fast. First, mixed-effects logistic regression analysis of choice accuracy showed that tVNS acutely impaired decision-making, p = .045. Computational reinforcement learning models identified the cause of this as a reduction in the learning rate through tVNS (Δα = −0.092, p boot = .002), particularly after punishment (Δα Pun = −0.081, p boot = .012 vs. Δα Rew = −0.031, p = .22). However, tVNS had no effect on go biases, Pavlovian response biases or response time. Hence, tVNS appeared to influence learning rather than action execution. These results highlight a novel role of vagal afferent input in modulating reinforcement learning by tuning the learning rate according to homeostatic needs.
Recent advances and future directions in mantle cell lymphoma research: report of the 2018 mantle cell lymphoma consortium workshop
2019-01-30

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma characterized by the t(11;14) chromosomal translocation. This translocation most often results in overexpression of cyclin D1. MCL is clinically heterogeneous, outcomes are generally poor, and no standard treatment has been established. The recent approvals of ibrutinib and acalabrutinib have provided an additional therapeutic option; however, resistance has emerged as a significant issue and presents the need for more detailed studies of resistance mechanisms. Recent clinical trials have provided new perspectives on the relative efficacy and safety of various approaches for both transplant-eligible and transplant-ineligible patients. Multiple novel strategies are being evaluated in the treatment of MCL, including both targeted agents and cellular immunotherapies. At the Lymphoma Research Foundation's 13th MCL Workshop, researchers gathered to discuss research findings, clinical trial results, and future directions related to MCL, its biology, and its treatment. This report, which includes a summary of each presentation, aims to review recent findings in MCL research and highlight potential areas for future study.
The Integration Functions of Topic Chains in Chinese Discourse
2019-01-30

The topic chain, one of the essential organization devices in Chinese discourse, is highlighted by the use of many co-referential zero forms. Although the topic chain has been realized to play an important role in organizing discourse, few attempts have been made to explore how the topic chain forms an integrated and meaningful unit and facilitates discourse organization, which are called the “integration functions” of the topic chain in this paper. This study, based on a comprehensive review of topic chain studies, re-examines the core characteristics of the topic chain. After this, the integration functions of the topic chain are analysed from internal and external levels. The topic chain itself can manage its internally different clauses to form a cohesive, meaningful and unified unit. At this stage, this paper clearly demonstrates why so much information within a topic chain is assembled into such a compact structure. At the discourse level, one topic chain can associate with other topic chains or non-chain constructions to establish textual coherence. Making use of zero anaphora, co-reference, cognitive orders and other non-morph-syntactic devices, the topic chain can combine different discourse units together to construct Chinese discourse. The study provides a systematic and well-developed account of the integration functions for the topic chain, which is significant for a deeper understanding of the nature of the topic chain and how discourse coherence is established in Chinese.
The strikingflower-in-flowerphenotype ofArabidopsis thalianaNossen (No-0) is caused by a novelLEAFYallele
2019-01-30

Summary The transition to reproduction is a crucial step in the life cycle of any organism. In Arabidopsis thaliana the establishment of reproductive growth can be divided into two phases: In the first phase, cauline leaves with axillary meristems are formed and internode elongation begins. In the second phase, lateral meristems develop into flowers with defined organs. Floral shoots are usually determinate and suppress the development of lateral shoots. Here, we describe a Ds transposon insertion mutant in the Nossen (No-0) accession with severe defects in floral development and flower morphology. The most striking aspect is the outgrowth of stems from the axillary bracts of the primary flower carrying terminal secondary flowers. Therefore, we named this mutant flower-in-flower ( fif ). However, the insertion of the transposon in the annotated gene is not responsible for the fif phenotype. By means of classical and genome sequencing-based mapping, the mutation responsible for the fif phenotype was found to be in the LEAFY ( LFY ) gene. The mutation, a G-to-A exchange in the second exon of LFY , creates a novel lfy allele and causes a cysteine-to-tyrosine exchange in the α1-helix of the LFY DNA-binding domain. Whereas subcellular localization and homomerization are not affected, the DNA-binding of LFY FIF is abolished. We propose that the amino acid exchange interferes with the cooperative binding of LFY to its target DNA. To generate the strong fif phenotype, LFY FIF may act dominant-negatively by either forming non-binding LFY/LFY FIF heteromers or by titrating out the interaction partners, required for LFY function as transcription factor. Significant Statement: The fif phenotype of Arabidopsis thaliana No-0 is caused by a novel allele of the LEAFY gene
Monkey EEG links neuronal color and motion information across species and scales
2019-01-30

Abstract It remains challenging to relate EEG and MEG to underlying circuit processes and comparable experiments on both spatial scales are rare. To close this gap between invasive and non-invasive electrophysiology we developed and recorded human-comparable EEG in macaque monkeys during visual stimulation with colored dynamic random dot patterns. Furthermore, we performed simultaneous microelectrode recordings from 6 areas of macaque cortex and human MEG. Motion direction and color information were accessible in all signal types. Tuning of the non-invasive signals was similar to V4 and IT, but not to dorsal and frontal areas. Thus, MEG and EEG were dominated by early visual and ventral stream sources. Source level analysis revealed corresponding information and latency gradients across the cortex. We show how information-based methods and monkey EEG can identify analogous properties of visual processing in signals spanning spatial scales from single units to MEG – a valuable framework for relating human and animal studies.
Terpenoids
2019-01-30

This chapter presents a brilliant approach for modern isolation and structure elucidation of terpenoids. It includes background, in-depth information about isolation processes and structural characterization as well as a Q&A section. Linalool is derived from Brazilian rosewood oil and Russian coriander oil. Linalool is an open chain tertiary monoterpene alcohol that occurs for example in the scent of flowers and in spices. The chapter describes the phytogenic sources of both linalools and their isolation by distillation of essential oils. Linalool can be used as a fragrance in washing agents and cosmetics; it is also a component in the synthesis of the vitamin E group. Coriander is an annual plant of the umbellifer family that since antiquity has been cultivated as a medicinal and spice plant. Coriander gets its name from the smell of true bugs which the fresh herb has. Coriander belongs to the oldest spices used.
Alkaloids
2019-01-30

This chapter presents a brilliant approach for modern isolation and structure elucidation of alkaloids. It includes background, in-depth information about isolation processes and structural characterization as well as a Q&A section. Pseudopelletierine is derived from the root-bark of the pomegranate tree. The chapter explains the the synthesis of cyclooctatetraene (COT) from pseudopelletierine. COT is not planar but in its most stable form exists in a tub-shaped conformation. Basic alkaloids occur in plants most often with a protonated amino function, i.e. in cationic form. The basicity of the alkaloid is used to differentiate it from the other lipophilic, organic substances. Pseudopelletierine is a homologue of tropinone. Pseudopelletierine proved to be a stroke of luck for the up-and-coming organic chemistry of the 20th century. The root-bark of the pomegranate tree is a speciality and a natural product that is not always commercially available.