julilili42/papers huggingface dataset:
Comment on Hedderson et al. Prepregnancy SHBG Concentrations and Risk for Subsequently Developing Gestational Diabetes Mellitus. Diabetes Care 2014;37:1296–1303
2014-11-08

Hedderson et al. (1) recently found that lower sex hormone–binding globulin (SHBG) concentrations measured, on average, 6 years before pregnancy were associated with increased odds of the development of gestational diabetes mellitus (GDM). Because this relationship was independent of known risk factors of GDM, they concluded that circulating SHBG may represent a potentially useful new biomarker for identifying who is at risk for GDM beyond the currently established clinical and demographic risk factors, in particular insulin resistance. While the study appears to be well performed and the data are very interesting, the conclusion with respect to insulin resistance may be overstated. In their study, Hedderson et al. could estimate ...
GP130 activation induces myeloma and collaborates with MYC
2014-11-09

Multiple myeloma (MM) is a plasma cell neoplasm that results from clonal expansion of an Ig-secreting terminally differentiated B cell. Advanced MM is characterized by tissue damage that involves bone, kidney, and other organs and is typically associated with recurrent genetic abnormalities. IL-6 signaling via the IL-6 signal transducer GP130 has been implicated as an important driver of MM pathogenesis. Here, we demonstrated that ectopic expression of constitutively active GP130 (L-GP130) in a murine retroviral transduction-transplantation model induces rapid MM development of high penetrance. L-GP130-expressing mice recapitulated all of the characteristics of human disease, including monoclonal gammopathy, BM infiltration with lytic bone lesions, and protein deposition in the kidney. Moreover, the disease was easily transplantable and allowed different therapeutic options to be evaluated in vitro and in vivo. Using this model, we determined that GP130 signaling collaborated with MYC to induce MM and was responsible and sufficient for directing the plasma cell phenotype. Accordingly, we identified Myc aberrations in the L-GP130 MM model. Evaluation of human MM samples revealed recurrent activation of STAT3, a downstream target of GP130 signaling. Together, our results indicate that deregulated GP130 activity contributes to MM pathogenesis and that pathways downstream of GP130 activity have potential as therapeutic targets in MM.
Generation of dense statistical connectomes from sparse morphological data
2014-11-10

Sensory-evoked signal flow, at cellular and network levels, is primarily determined by the synaptic wiring of the underlying neuronal circuitry. Measurements of synaptic innervation, connection probabilities and subcellular organization of synaptic inputs are thus among the most active fields of research in contemporary neuroscience. Methods to measure these quantities range from electrophysiological recordings over reconstructions of dendrite-axon overlap at light-microscopic levels to dense circuit reconstructions of small volumes at electron-microscopic resolution. However, quantitative and complete measurements at subcellular resolution and mesoscopic scales to obtain all local and long-range synaptic in/outputs for any neuron within an entire brain region are beyond present methodological limits. Here, we present a novel concept, implemented within an interactive software environment called NeuroNet, which allows (i) integration of sparsely sampled (sub)cellular morphological data into an accurate anatomical reference frame of the brain region(s) of interest, (ii) up-scaling to generate an average dense model of the neuronal circuitry within the respective brain region(s) and (iii) statistical measurements of synaptic innervation between all neurons within the model. We illustrate our approach by generating a dense average model of the entire rat vibrissal cortex, providing the required anatomical data, and illustrate how to measure synaptic innervation statistically. Comparing our results with data from paired recordings in vitro and in vivo, as well as with reconstructions of synaptic contact sites at light- and electron-microscopic levels, we find that our in silico measurements are in line with previous results.
Linking Online Gaming and Addictive Behavior: Converging Evidence for a General Reward Deficiency in Frequent Online Gamers
2014-11-10

Millions of people regularly play so-called massively multiplayer online role playing games (MMORPGs). Recently, it has been argued that MMORPG overuse is becoming a significant health problem worldwide. Symptoms such as tolerance, withdrawal, and craving have been described. Based on behavioral, resting state, and task-related neuroimaging data, we test whether frequent players of the MMORPG "World of Warcraft" (WoW) - similar to drug addicts and individuals with an increased risk for addictions - show a generally deficient reward system. In frequent players of the MMORPG "World of Warcraft" (WoW-players) and in a control group of non-gamers we assessed (1) trait sensitivity to reward (SR), (2) BOLD responses during monetary reward processing in the ventral striatum, and (3) ventral-striatal resting-state dynamics. We found a decreased neural activation in the ventral striatum during the anticipation of both small and large monetary rewards. Additionally, we show generally altered neurodynamics in this region independent of any specific task for WoW players (resting state). On the behavioral level, we found differences in trait SR, suggesting that the reward processing deficiencies found in this study are not a consequence of gaming, but predisposed to it. These findings empirically support a direct link between frequent online gaming and the broad field of behavioral and drug addiction research, thus opening new avenues for clinical interventions in addicted gamers and potentially improving the assessment of addiction-risk in the vast population of frequent gamers.
Photodegradation of C‐PCPDTBT and Si‐PCPDTBT: Influence of the Bridging Atom on the Stability of a Low‐Band‐Gap Polymer for Solar Cell Application
2014-11-10

Abstract The kinetics of photodegradation and the reactivity of different sites of the low‐band‐gap polymers poly[2,6‐(4,4‐ bis ‐(2‐ethylhexyl)‐4 H ‐cyclopenta[2,1‐ b :3,4‐ b ′]dithiophene)‐ alt ‐4,7‐(2,1,3‐benzothiadiazole)] (C‐PCPDTBT) and poly[2,6‐(4,4‐ bis ‐(2‐ethylhexyl)dithieno[3,2‐ b :2′,3′‐ d ]silole)‐ alt ‐4,7‐(2,1,3‐benzothiadiazole)] (Si‐PCPDTBT) are investigated as thin films and are compared to those of poly(3‐hexylthiophene) (P3HT). The decay kinetics are monitored with UV/Vis spectroscopy and the reactivity and product evolution are investigated with X‐ray photoelectron spectroscopy (XPS). Both polymers exhibit higher stability than P3HT. The bridging atom in the cyclopentadithiophene (CPDT) subunit has a significant influence on the stability. Varying oxidation rates for the different elements were observed. In the case of Si‐PCPDTBT, the silicon atom is oxidized primarily, whereas the photooxidation rates of the other elements are reduced relative to C‐PCPDTBT. Additionally, XPS experiments with varying excitation energies reveal a significant reaction gradient within a few nanometers of the surface of degraded thin films of C‐PCPDTBT.
Absolute configuration assignment of a chiral molecule in the gas phase using foil-induced Coulomb explosion imaging
2014-11-10

Chiral molecules exist in two configurations that are nonsuperposable mirror images of one another. The underlying molecular structure is referred to as the absolute configuration. In chiral environments, the handedness of molecules influences their chemical characteristics dramatically, and therefore the determination of absolute configurations is of fundamental interest in organic chemistry and biology. Commonly applied techniques to assign absolute configuration are anomalous single-crystal x-ray diffraction and vibrational circular dichroism. However, these techniques become increasingly more challenging when applied to molecules that are made out of light atoms exclusively. Furthermore, there is no established method to determine the absolute handedness of gas-phase molecules that are not optically active. In this work, we apply the foil-induced Coulomb explosion imaging technique to determine directly the absolute configuration of the chiral molecule trans-2,3-dideuterooxirane ( ) in the gas phase. The experiment leads to the definitive assignment of the ( ) configuration to an enantio-selected dideuterooxirane sample with a statistical confidence of . As the handedness of trans-2,3-dideuterooxirane is unambiguously linked by chemical synthesis to the stereochemical key reference glyceraldehyde, our results provide an independent verification of the absolute configuration of the stereochemical reference standard.
Variants inCUL4Bare Associated with Cerebral Malformations
2014-11-11

Variants in cullin 4B (CUL4B) are a known cause of syndromic X-linked intellectual disability. Here, we describe an additional 25 patients from 11 families with variants in CUL4B. We identified nine different novel variants in these families and confirmed the pathogenicity of all nontruncating variants. Neuroimaging data, available for 15 patients, showed the presence of cerebral malformations in ten patients. The cerebral anomalies comprised malformations of cortical development (MCD), ventriculomegaly, and diminished white matter volume. The phenotypic heterogeneity of the cerebral malformations might result from the involvement of CUL-4B in various cellular pathways essential for normal brain development. Accordingly, we show that CUL-4B interacts with WDR62, a protein in which variants were previously identified in patients with microcephaly and a wide range of MCD. This interaction might contribute to the development of cerebral malformations in patients with variants in CUL4B.
Automatic CEFR Level Prediction for Estonian Learner Text
2014-11-11

This paper reports on approaches for automatically predicting a learner’s language proficiency in Estonian according to the European CEFR scale. We used the morphological and POS tag information extracted from the texts written by learners. We compared classification and regression modeling for this task. Our models achieve a classification accuracy of 79 % and a correlation of 0.85 when modeled as regression. After a comparison between them, we concluded that classification is more effective than regression in terms of exact error and the direction of error. Apart from this, we investigated the most predictive features for both multi-class and binary classification between groups and also explored the nature of the correlations between highly predictive features. Our results show considerable improvement in classification accuracy over previously reported results and take us a step closer towards the automated assessment of Estonian learner text.
A VIEW of Russian: Visual Input Enhancement and Adaptive Feedback
2014-11-11

We explore the challenges and opportunities which arise in developing automatic visual input enhancement activities for Russian with a focus on target selection and adaptive feedback. Russian, a language with a rich fusional morphology, has many syntactically relevant forms that are not transparent to the language learner, which makes it a good candidate for visual input enhancement (VIE). VIE essentially supports incidental focus on form by increasing the salience of language forms to support noticing by the learner. The freely available VIEW system (Meurers et al., 2010) was designed to automatically generate VIE activities from any web content. We extend VIEW to Russian and discuss connected research issues regarding target selection, ambiguity management, prompt generation, and distractor generation. We show that the same information and techniques used for target selection can often be repurposed for adaptive feedback. Authentic Text ICALL (ATICALL) systems incorporating only native-language NLP, without the NLP analysis specific to learner language that is characteristic of Intelligent Language Tutoring Systems (ILTS), thus can support some forms of adaptive feedback. ATICALL and ILTS represent a spectrum of possibilities rather than two categorically distinct enterprises.
Ion-activated attractive patches as a mechanism for controlled protein interactions
2014-11-12

The understanding of protein interactions to control phase and nucleation behavior of protein solutions is an important challenge for soft matter, biological and medical research. Here, we present ion bridges of multivalent cations between proteins as an ion-activated mechanism for patchy interaction that is directly supported by experimental findings in protein crystals. A deep understanding of experimentally observed phenomena in protein solutions--including charge reversal, reentrant condensation, metastable liquid-liquid phase separation, cluster formation and different pathways of crystallization--is gained by an analytic model that directly displays parameter dependencies and physical connections. The direct connection between experiment and theory provides a conceptual framework for future experimental, computational and theoretical research on topics such as rational design of phase behavior and crystallization pathways on the basis of the statistical physics of patchy particles.
Featured Article: Isolation, characterization, and cultivation of human hepatocytes and non-parenchymal liver cells
2014-11-12

Primary human hepatocytes (PHH) are considered to be the gold standard for in vitro testing of xenobiotic metabolism and hepatotoxicity. However, PHH cultivation in 2D mono-cultures leads to dedifferentiation and a loss of function. It is well known that hepatic non-parenchymal cells (NPC), such as Kupffer cells (KC), liver endothelial cells (LEC), and hepatic stellate cells (HSC), play a central role in the maintenance of PHH functions. The aims of the present study were to establish a protocol for the simultaneous isolation of human PHH and NPC from the same tissue specimen and to test their suitability for in vitro co-culture. Human PHH and NPC were isolated from tissue obtained by partial liver resection by a two-step EDTA/collagenase perfusion technique. The obtained cell fractions were purified by Percoll density gradient centrifugation. KC, LEC, and HSC contained in the NPC fraction were separated using specific adherence properties and magnetic activated cell sorting (MACS®). Identified NPC revealed a yield of 1.9 × 10 6 KC, 2.7 × 10 5 LEC and 4.7 × 10 5 HSC per gram liver tissue, showing viabilities &gt;90%. Characterization of these NPC showed that all populations went through an activation process, which influenced the cell fate. The activation of KC strongly depended on the tissue quality and donor anamnesis. KC became activated in culture in association with a loss of viability within 4–5 days. LEC lost specific features during culture, while HSC went through a transformation process into myofibroblasts. The testing of different culture conditions for HSC demonstrated that they can attenuate, but not prevent dedifferentiation in vitro. In conclusion, the method described allows the isolation and separation of PHH and NPC in high quality and quantity from the same donor.
How Laypeople Understand the Tentativeness of Medical Research News in the Media
2014-11-12

Medical research findings are often tentative, and people should be able to perceive this. However, the psychological processes underlying this ability are largely unclear. In a laboratory experiment, we found that the following factors had an impact on perception of tentativeness of research findings reported in a newspaper article: (a) the framing of findings, (b) emphasis on the limited reliability of the findings in the article, (c) people’s provisional opinion on the topic, and (d) their medicine-related epistemological beliefs. We make recommendations to science journalists to help promote the public understanding of health research and provide suggestions for future studies.
Identification of a Common Non-Apoptotic Cell Death Mechanism in Hereditary Retinal Degeneration
2014-11-13

Cell death in neurodegenerative diseases is often thought to be governed by apoptosis; however, an increasing body of evidence suggests the involvement of alternative cell death mechanisms in neuronal degeneration. We studied retinal neurodegeneration using 10 different animal models, covering all major groups of hereditary human blindness (rd1, rd2, rd10, Cngb1 KO, Rho KO, S334ter, P23H, Cnga3 KO, cpfl1, Rpe65 KO), by investigating metabolic processes relevant for different forms of cell death. We show that apoptosis plays only a minor role in the inherited forms of retinal neurodegeneration studied, where instead, a non-apoptotic degenerative mechanism common to all mutants is of major importance. Hallmark features of this pathway are activation of histone deacetylase, poly-ADP-ribose-polymerase, and calpain, as well as accumulation of cyclic guanosine monophosphate and poly-ADP-ribose. Our work thus demonstrates the prevalence of alternative cell death mechanisms in inherited retinal degeneration and provides a rational basis for the design of mutation-independent treatments.
Controlling the magnetic-field sensitivity of atomic-clock states by microwave dressing
2014-11-13

We demonstrate control of the differential Zeeman shift between clock states of ultracold rubidium atoms by means of non-resonant microwave dressing. Using the dc-field dependence of the microwave detuning, we suppress the first and second order differential Zeeman shift in magnetically trapped Rb atoms. By dressing the state pair 5S and , a residual frequency spread of <0.1 Hz in a range of 100 mG around a chosen magnetic offset field can be achieved. This is one order of magnitude smaller than the shift of the bare states at the magic field of the Breit-Rabi parabola. We further identify double magic points, around which the clock frequency is insensitive to fluctuations both in the magnetic field and the dressing Rabi frequency. The technique is compatible with chip-based cold atom systems and allows the creation of clock and qubit states with reduced sensitivity to magnetic field noise.
Rare‐Earth‐Metal Methyl, Amide, and Imide Complexes Supported by a Superbulky Scorpionate Ligand
2014-11-13

Abstract The reaction of monomeric [(Tp t Bu,Me )LuMe 2 ] (Tp t Bu,Me =tris(3‐Me‐5‐ t Bu‐pyrazolyl)borate) with primary aliphatic amines H 2 NR (R= t Bu, Ad=adamantyl) led to lutetium methyl primary amide complexes [(Tp t Bu,Me )LuMe(NHR)], the solid‐state structures of which were determined by XRD analyses. The mixed methyl/tetramethylaluminate compounds [(Tp t Bu,Me )LnMe({μ 2 ‐Me}AlMe 3 )] (Ln=Y, Ho) reacted selectively and in high yield with H 2 NR, according to methane elimination, to afford heterobimetallic complexes: [(Tp t Bu,Me )Ln({μ 2 ‐Me}AlMe 2 )(μ 2 ‐NR)] (Ln=Y, Ho). X‐ray structure analyses revealed that the monomeric alkylaluminum‐supported imide complexes were isostructural, featuring bridging methyl and imido ligands. Deeper insight into the fluxional behavior in solution was gained by 1 H and 13 C NMR spectroscopic studies at variable temperatures and 1 H– 89 Y HSQC NMR spectroscopy. Treatment of [(Tp t Bu,Me )LnMe(AlMe 4 )] with H 2 N t Bu gave dimethyl compounds [(Tp t Bu,Me )LnMe 2 ] as minor side products for the mid‐sized metals yttrium and holmium and in high yield for the smaller lutetium. Preparative‐scale amounts of complexes [(Tp t Bu,Me )LnMe 2 ] (Ln=Y, Ho, Lu) were made accessible through aluminate cleavage of [(Tp t Bu,Me )LnMe(AlMe 4 )] with N , N , N ′, N ′‐tetramethylethylenediamine (tmeda). The solid‐state structures of [(Tp t Bu,Me )HoMe(AlMe 4 )] and [(Tp t Bu,Me )HoMe 2 ] were analyzed by XRD.
<em>In Vitro</em> Synthesis of Modified mRNA for Induction of Protein Expression in Human Cells
2014-11-13

The exogenous delivery of coding synthetic messenger RNA (mRNA) for induction of protein synthesis in desired cells has enormous potential in the fields of regenerative medicine, basic cell biology, treatment of diseases, and reprogramming of cells. Here, we describe a step by step protocol for generation of modified mRNA with reduced immune activation potential and increased stability, quality control of produced mRNA, transfection of cells with mRNA and verification of the induced protein expression by flow cytometry. Up to 3 days after a single transfection with eGFP mRNA, the transfected HEK293 cells produce eGFP. In this video article, the synthesis of eGFP mRNA is described as an example. However, the procedure can be applied for production of other desired mRNA. Using the synthetic modified mRNA, cells can be induced to transiently express the desired proteins, which they normally would not express.
Three‐Dimensional Mid‐Infrared Tomographic Imaging of Endogenous and Exogenous Molecules in a Single Intact Cell with Subcellular Resolution
2014-11-13

Abstract Microscopy in the mid‐infrared spectral range provides detailed chemical information on a sample at moderate spatial resolution and is being used increasingly in the characterization of biological entities as challenging as single cells. However, a conventional cellular 2D imaging measurement is limited in its ability to associate specific compositional information to subcellular structures because of the interference from the complex topography of the sample. Herein we provide a method and protocols that overcome this challenge in which tilt‐series infrared tomography is used with a standard benchtop infrared microscope. This approach gives access to the quantitative 3D distribution of molecular components based on the intrinsic contrast provided by the sample. We demonstrate the method by quantifying the distribution of an exogenous metal carbonyl complex throughout the cell and by reporting changes in its coordination sphere in different locations in the cell.
Characterization of K-Complexes and Slow Wave Activity in a Neural Mass Model
2014-11-13

NREM sleep is characterized by two hallmarks, namely K-complexes (KCs) during sleep stage N2 and cortical slow oscillations (SOs) during sleep stage N3. While the underlying dynamics on the neuronal level is well known and can be easily measured, the resulting behavior on the macroscopic population level remains unclear. On the basis of an extended neural mass model of the cortex, we suggest a new interpretation of the mechanisms responsible for the generation of KCs and SOs. As the cortex transitions from wake to deep sleep, in our model it approaches an oscillatory regime via a Hopf bifurcation. Importantly, there is a canard phenomenon arising from a homoclinic bifurcation, whose orbit determines the shape of large amplitude SOs. A KC corresponds to a single excursion along the homoclinic orbit, while SOs are noise-driven oscillations around a stable focus. The model generates both time series and spectra that strikingly resemble real electroencephalogram data and points out possible differences between the different stages of natural sleep.
Omega-3 fatty acid concentrate fromDunaliella salinapossesses anti-inflammatory properties including blockade of NF-κB nuclear translocation
2014-11-13

The health benefits of omega-3 polyunsaturated fatty acids (ω-3 PUFA), mainly eicosapentaenoic acid (EPA 20:5) and docosahexaenoic acid (DHA, 22:6), have been long known. Although various studies have demonstrated the health benefits of ω-3 PUFA, the mechanisms of action of ω-3 PUFAs are still not completely understood. While the major commercial source is marine fish oil, in this study we suggest the marine micro algae, Dunaliella salina as an alternate source of omega-3 fatty acids. Treatment with this algal omega-3 fatty acid concentrate (Ds-ω-3 FA) resulted in significant down-regulation of LPS-induced production of TNF-α and IL-6 by peripheral blood mononuclear cells (PBMCs). The concentrate was also found to be a potent blocker of cyclooxygenase (COX-2) and matrix metalloproteinase (MMP-2 and MMP-9) expression. The present study reveals the anti-inflammatory properties of Ds-ω-3 FA concentrate including the inhibition of NF-κB translocation.