julilili42/papers huggingface dataset:
Generation of a human induced pluripotent stem cell (iPSC) line from a patient with family history of diabetes carrying a C18R mutation in the PDX1 gene
2016-08-07

Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor PDX1 leads to pancreatic agenesis, whereas certain heterozygous point mutations are associated with Maturity-Onset Diabetes of the Young 4 (MODY4) and Type 2 Diabetes Mellitus (T2DM). To understand the pathomechanism of MODY4 and T2DM, we have generated iPSCs from a woman with a C18R heterozygous mutation in the transactivation domain of PDX1. The resulting PDX1 C18R iPSCs generated by episomal reprogramming are integration-free, have a normal karyotype and are pluripotent in vitro and in vivo. Taken together, this iPSC line will be useful to study diabetes pathomechanisms.
Hybrid Neuroprosthesis for the Upper Limb: Combining Brain-Controlled Neuromuscular Stimulation with a Multi-Joint Arm Exoskeleton
2016-08-08

Brain-machine interface-controlled (BMI) neurofeedback training aims to modulate cortical physiology and is applied during neurorehabilitation to increase the responsiveness of the brain to subsequent physiotherapy. In a parallel line of research, robotic exoskeletons are used in goal-oriented rehabilitation exercises for patients with severe motor impairment to extend their range of motion (ROM) and the intensity of training. Furthermore, neuromuscular electrical stimulation (NMES) is applied in neurologically impaired patients to restore muscle strength by closing the sensorimotor loop. In this proof-of-principle study, we explored an integrated approach for providing assistance as needed to amplify the task-related ROM and the movement-related brain modulation during rehabilitation exercises of severely impaired patients. For this purpose, we combined these three approaches (BMI, NMES, and exoskeleton) in an integrated neuroprosthesis and studied the feasibility of this device in seven severely affected chronic stroke patients who performed wrist flexion and extension exercises while receiving feedback via a virtual environment. They were assisted by a gravity-compensating, seven degree-of-freedom exoskeleton which was attached to the paretic arm. NMES was applied to the wrist extensor and flexor muscles during the exercises and was controlled by a hybrid BMI based on both sensorimotor cortical desynchronization (ERD) and electromyography (EMG) activity. The stimulation intensity was individualized for each targeted muscle and remained subthreshold, i.e., induced no overt support. The hybrid BMI controlled the stimulation significantly better than the offline analyzed ERD (p = 0.028) or EMG (p = 0.021) modality alone. Neuromuscular stimulation could be well integrated into the exoskeleton-based training and amplified both the task-related ROM (p = 0.009) and the movement-related brain modulation (p = 0.019). Combining a hybrid BMI with neuromuscular stimulation and antigravity assistance augments upper limb function and brain activity during rehabilitation exercises and may thus provide a novel restorative framework for severely affected stroke patients.
POST-TEXT III and IV Hepatoblastoma
2016-08-09

Aggressive surgical resection is a successful approach in some patients with POST-TEXT III and IV HB who otherwise would be candidates for liver transplantation. These children should undergo central review and should be surgically managed at centers of excellence for pediatric liver surgery. Despite challenging surgical procedures and complex clinical courses, the patients benefit from avoidance of morbidities of organ transplant. However, preparation of backup liver transplantation should be considered in selected cases.
How open is too open? The mitigating role of appropriation mechanisms in R&D cooperation settings
2016-08-09

In this article, we investigate the influence of firms’ R&amp;D cooperation activities on their likelihood to experience imitation. Analyses of firm‐level survey data concerning the R&amp;D cooperation behavior of 2,797 German firms reveal that companies engaging in R&amp;D cooperation face significantly more imitation than their peers that do not cooperate on R&amp;D. Further, we show that cooperation with all potential collaboration partner types except universities and research institutions and in all phases of the innovation process increases the risk of imitation. While we find evidence that intellectual property rights (IPR) generally work well as governance mechanisms moderating the relationship between R&amp;D cooperation and imitation, contracts do not. Hence, IPR apparently provide better protection against imitation than contracts. Our findings indicate that the risks associated with firms’ increased engagement in R&amp;D cooperation could eventually harm the production of new knowledge.
Post-translational Serine/Threonine Phosphorylation and Lysine Acetylation: A Novel Regulatory Aspect of the Global Nitrogen Response Regulator GlnR in S. coelicolor M145
2016-08-09

Soil-dwelling Streptomyces bacteria such as S.coelicolor have to constantly adapt to the nitrogen (N) availability in their habitat. Thus, strict transcriptional and post-translational control of the N-assimilation is fundamental for survival of this species. GlnR is a global response regulator that controls transcription of the genes related to the N-assimilation in S. coelicolor and other members of the Actinomycetales. GlnR represents an atypical orphan response regulator that is not activated by the phosphorylation of the conserved aspartate residue (Asp 50). We have applied transcriptional analysis, LC-MS/MS analysis and electrophoretic mobility shift assays (EMSAs) to understand the regulation of GlnR in S. coelicolor M145. The expression of glnR and GlnR-target genes was revisited under four different N-defined conditions and a complex N-rich condition. Although, the expression of selected GlnR-target genes was strongly responsive to changing N-concentrations, the glnR expression itself was independent of the N-availability. Using LC-MS/MSanalysis we demonstrated that GlnR was post-translationally modified. The post-translational modifications of GlnR comprise phosphorylation of the serine/threonine residues and acetylation of lysine residues. In the complex N-rich medium GlnR was phosphorylated on six serine/threonine residues and acetylated on one lysine residue. Under defined N-excess conditions only two phosphorylated residues were detected whereas under defined N-limiting conditions no phosphorylation was observed. GlnR phosphorylation is thus clearly correlated with N-rich conditions. Furthermore, GlnR was acetylated on four lysine residues independently of the N-concentration in the defined media and on only one lysine residue in the complex N-rich medium. Using EMSAs we demonstrated that phosphorylation inhibited the binding of GlnR to its targets genes, whereas acetylation had little influence on the formation of GlnR-DNA complex. This study clearly demonstrated that GlnR DNA-binding affinity is modulated by post-translational modifications in response to changing N-conditions in order to elicit a proper transcriptional response to the latter.
Site-Specific Ligand Interactions Favor the Tetragonal Distortion of PbS Nanocrystal Superlattices
2016-08-09

We analyze the structure and morphology of mesocrystalline, body-centered tetragonal (bct) superlattices of PbS nanocrystals functionalized with oleic acid. On the basis of combined scattering and real space imaging, we derive a three-dimensional (3D) model of the superlattice and show that the bct structure benefits from a balanced combination of {100}PbS-{100}PbS and {111}PbS-{111}PbS interactions between neighboring layers of nanocrystals, which uniquely stabilizes this structure. These interactions are enabled by the coaxial alignment of the atomic lattices of PbS with the superlattice. In addition, we find that this preferential orientation is already weakly present within isolated monolayers. By adding excess oleic acid to the nanocrystal solution, tetragonal distortion is suppressed, and we observe assembly into a bilayered hexagonal lattice reminiscent of a honeycomb with grain sizes of several micrometers.
Is it all task-specific? The role of binary responses, verbal mediation, and saliency for eliciting language-space associations.
2016-08-09

Associations between language and space are of central interest for grounded models of language comprehension. Various studies show that reading words such as bird or shoe results in faster responses toward the typical location of the corresponding entity (e.g., after bird, upward responses are faster than downward responses). Critically, as of yet, the mechanisms underlying these effects and their boundary conditions are widely unknown. In fact, it cannot be ruled out that these effects are by-products of processing that only occur in very specific task settings. Here we investigated the role of 3 major processes (response set, labeling, and saliency) that might underlie these compatibility effects in Stroop-like paradigms. In Experiment 1, we aimed at overcoming the binary nature of the response set by including responses both in the vertical and the horizontal dimension. In Experiment 2 no memorizing of the color-to-response mapping was required, making internal response labeling unnecessary. In Experiment 3 this was replicated in a mouse-tracking setup. In all experiments a clear language-space association was observed. Critically, in a final experiment not only the saliency of verticality in the response set but also in the stimulus set was reduced. Here no language-space association was observed. Together these results suggest that language-space associations extend beyond bipolar response settings and that internal response labeling is not a precondition for finding these compatibility effects. However, the vertical dimension needs to be salient either in the stimulus or response set. Implications for models of language comprehension are discussed. (PsycINFO Database Record
J(Si,H) Coupling Constants in Nonclassical Transition‐Metal Silane Complexes
2016-08-09

Abstract We will outline that the sign and magnitude of J (Si,H) coupling constants provide a highly sensitive tool to measure the extent of Si−H bond activation in nonclassical silane complexes. Up to now, this structure–property relationship was obscured by erroneous J (Si,H) sign determinations in the literature. These new findings also help to identify the salient control parameters of the Si−H bond activation process in nonclassical silane complexes.
Efficacy and safety of Dexrazoxane (DRZ) in sarcoma patients receiving high cumulative doses of anthracycline therapy – a retrospective study including 32 patients
2016-08-09

Chemotherapy with high cumulative doses of anthracyclines in addition with DRZ demonstrated a remarkable OS in these advanced disease patients. Cardiac side-effects due to high cumulative doses of anthracyclines requiring discontinuation of anthracycline treatment were rare. A PFS of 9 months from the beginning of the coadministration of DRZ indicates that continuing anthracycline therapy beyond established cumulative doses is a promising therapeutic option.
Eu2(CN2)3 and KEu[Si(CN2)4]: Missing Members of the Rare Earth Metal Carbodiimide and Tetracyanamidosilicate Series
2016-08-09

Europium(III) compounds with the compositions Eu 2 (CN 2 ) 3 and KEu[Si(CN 2 ) 4 ] were prepared by solid‐state metathesis reactions. The europium(III) carbodiimide was prepared by the reaction of EuF 3 and Li 2 CN 2 , while the europium(III) tetracyanamidosilicate was prepared from EuF 3 , K 2 SiF 6 , and Li 2 CN 2 . Their crystal structures were refined from powder XRD data with space groups C 2/ m for Eu 2 (CN 2 ) 3 and P 2 1 2 1 2 for KEu[Si(CN 2 ) 4 ]. Luminescence spectra of Eu 2 (CN 2 ) 3 and KEu[Si(CN 2 ) 4 ] as well as nonlinear optical properties of KEu[Si(CN 2 ) 4 ] are reported. The two synthesized compounds are the missing members of the rare earth metal carbodiimide and tetracyanamidosilicate series.
Novel mouse model for primary uveal melanoma: a pilot study
2016-08-09

Abstract Background To establish a mouse model with the aim of studying the tumour biology and metastasis formation of uveal melanoma. Methods Two human primary uveal melanoma cell lines (UMT2 and UMT42) were injected into the choroid of BALB/c nude mouse eyes. Intraocular tumour growth and metastasis formation in the liver and lungs were assessed after 13 to 22 weeks. Formalin‐fixed, paraffin‐embedded material was processed via haematoxylin and eosin staining for histological examination and periodic acid Schiff staining to search for extravascular matrix patterns. Immunohistochemistry for Melan A, CD34 and Ki67 was performed to assess the expression of a melanocytic lineage marker, angiogenesis and proliferative activity. Results All eyes injected with UMT2 cells, but only 25% of eyes treated with UMT42, developed intraocular tumour growth. The morphology of intraocular melanomas resembled that of primary tumours and showed signs of malignancy, including retinal invasion, optic nerve invasion and scleral penetration with extraocular tumour growth. UMT2 tumours formed extravascular matrix patterns exclusively. Most of the tumour cells expressed Melan A. Intratumoural angiogenesis was detected in both tumour entities. Proliferative activity was verified in all but one tumour. However, no metastases appeared in the liver or lungs. Conclusions The mouse model presented with the UMT2 cell line allows for investigations of tumour biology of the primary UM because of the high degree of similarity between the tumours generated in the mouse eyes and the corresponding primary human UM. Unfortunately, the model is not suitable for investigations of metastasis formation.
Clusterorganisationen in der Praxis
2016-08-09

Cluster organizations implement cluster policies and affect the outcome of them to a high degree. Their work is influenced by interactions with the promoted firms, political and other actors. A sound consultancy of cluster promotion should know these influences and take them seriously, because they shape the strengths, weaknesses and potentials of cluster organizations. This article examines how cluster organizations in Bavaria translate cluster theory into practical activities and how other actors influence them in the process. The influences are subdivided into institutional and structural factors. Institutional factors refer to social institutions that other actors impose on the organizations. It will be shown that these factors shape the work of cluster organizations to a high degree, but only seldom restrain it. The organizations positions and tasks within the wider economic promotion system constitute the structural factors. They confine the organizations towards networking activities and force them to cooperate with other promotional actors, if they want to provide a comprehensive cluster promotion.
KEPLER-1647B: THE LARGEST AND LONGEST-PERIOD KEPLER TRANSITING CIRCUMBINARY PLANET
2016-08-10

ABSTRACT We report the discovery of a new Kepler transiting circumbinary planet (CBP). This latest addition to the still-small family of CBPs defies the current trend of known short-period planets orbiting near the stability limit of binary stars. Unlike the previous discoveries, the planet revolving around the eclipsing binary system Kepler-1647 has a very long orbital period (∼1100 days) and was at conjunction only twice during the Kepler mission lifetime. Due to the singular configuration of the system, Kepler-1647b is not only the longest-period transiting CBP at the time of writing, but also one of the longest-period transiting planets. With a radius of 1.06 ± 0.01 R Jup , it is also the largest CBP to date. The planet produced three transits in the light curve of Kepler-1647 (one of them during an eclipse, creating a syzygy) and measurably perturbed the times of the stellar eclipses, allowing us to measure its mass, 1.52 ± 0.65 M Jup . The planet revolves around an 11-day period eclipsing binary consisting of two solar-mass stars on a slightly inclined, mildly eccentric ( e bin = 0.16), spin-synchronized orbit. Despite having an orbital period three times longer than Earth’s, Kepler-1647b is in the conservative habitable zone of the binary star throughout its orbit.
Intrinsic functional connectivity underlying successful emotion regulation of angry faces
2016-08-10

Most of our social interaction is naturally based on emotional information derived from the perception of faces of other people. Negative facial expressions of a counterpart might trigger negative emotions and initiate emotion regulatory efforts to reduce the impact of the received emotional message in a perceiver. Despite the high adaptive value of emotion regulation in social interaction, the neural underpinnings of it are largely unknown. To remedy this, this study investigated individual differences in emotion regulation effectiveness during the reappraisal of angry faces on the underlying functional activity using functional magnetic resonance imaging (fMRI) as well as the underlying functional connectivity using resting-state fMRI. Greater emotion regulation ability was associated with greater functional activity in the ventromedial prefrontal cortex. Furthermore, greater functional coupling between activity in the ventrolateral prefrontal cortex and the amygdala was associated with emotion regulation success. Our findings provide a first link between prefrontal cognitive control and subcortical emotion processing systems during successful emotion regulation in an explicitly social context.
Heritability of Caffeine Metabolism: Environmental Effects Masking Genetic Effects on CYP1A2 Activity but Not on NAT2
2016-08-10

Heritability of caffeine pharmacokinetics and cytochrome P450 1A2 (CYP1A2) activity is controversial. Here, we analyzed the pharmacokinetics of caffeine, an in vivo probe drug for CYP1A2 and arylamine N‐acetyltransferase 2 (NAT2) activity, in monozygotic (MZ) and dizygotic (DZ) twins. In the entire group, common and unique environmental effects explained most variation in caffeine area under the curve (AUC). Apparently, smoking and hormonal contraceptives masked the genetic effects on CYP1A2 activity. However, when excluding smokers and users of hormonal contraceptives, 89% of caffeine AUC variation was due to genetic effects and, even in the entire group, 8% of caffeine AUC variation could be explained by a CYP1A1/1A2 promotor polymorphism (rs2470893). In contrast, nearly all of the variations (99%) of NAT2 activity were explained by genetic effects. This study illustrates two very different situations in pharmacogenetics from an almost exclusively genetic determination of NAT2 activity with no environmental modulation to only moderate genetic effects on CYP1A2 activity with strong environmental modulation.
DJ‐1/Park7 Sensitive Na+/H+ Exchanger 1 (NHE1) in CD4+ T Cells
2016-08-10

DJ‐1/Park7 is a redox‐sensitive chaperone protein counteracting oxidation and presumably contributing to the control of oxidative stress responses and thus inflammation. DJ‐1 gene deletion exacerbates the progression of Parkinson's disease presumably by augmenting oxidative stress. Formation of reactive oxygen species (ROS) is paralleled by activation of the Na + /H + exchanger 1 (NHE1). ROS formation in CD4 + T cells plays a decisive role in regulating inflammatory responses. In the present study, we explored whether DJ‐1 is expressed in CD4 + T cells, and affects ROS production as well as NHE1 in those cells. To this end, DJ‐1 and NHE1 transcript, and protein levels were quantified by qRT‐PCR and Western blotting, respectively, intracellular pH (pH i ) utilizing bis‐(2‐carboxyethyl)‐5‐(and‐6)‐carboxyfluorescein (BCECF) fluorescence, NHE activity from realkalinization after an ammonium pulse, and ROS production utilizing 2′,7′ −dichlorofluorescin diacetate (DCFDA) fluorescence. As a result DJ‐1 was expressed in CD4 + T cells. ROS formation, NHE1 transcript levels, NHE1 protein, and NHE activity were higher in CD4 + T cells from DJ‐1 deficient mice than in CD4 + T cells from wild type mice. Antioxidant N‐acetyl‐cysteine (NAC) and protein tyrosine kinase (PTK) inhibitor staurosporine decreased the NHE activity in DJ‐1 deficient CD4 + T cells, and blunted the difference between DJ‐1 −/− and DJ‐1 +/+ CD4 + T cells, an observation pointing to a role of ROS in the up‐regulation of NHE1 in DJ‐1 −/− CD4 + T cells. In conclusion, DJ‐1 is a powerful regulator of ROS production as well as NHE1 expression and activity in CD4 + T cells. J. Cell. Physiol. 232: 3050–3059, 2017. © 2016 Wiley Periodicals, Inc.
Lipoproteins of Gram-Positive Bacteria: Key Players in the Immune Response and Virulence
2016-08-11

SUMMARY Since the discovery in 1973 of the first of the bacterial lipoproteins (Lpp) in Escherichia coli , Braun's lipoprotein, the ever-increasing number of publications indicates the importance of these proteins. Bacterial Lpp belong to the class of lipid-anchored proteins that in Gram-negative bacteria are anchored in both the cytoplasmic and outer membranes and in Gram-positive bacteria are anchored only in the cytoplasmic membrane. In contrast to the case for Gram-negative bacteria, in Gram-positive bacteria lipoprotein maturation and processing are not vital. Physiologically, Lpp play an important role in nutrient and ion acquisition, allowing particularly pathogenic species to better survive in the host. Bacterial Lpp are recognized by Toll-like receptor 2 (TLR2) of the innate immune system. The important role of Lpp in Gram-positive bacteria, particularly in the phylum Firmicutes , as key players in the immune response and pathogenicity has emerged only in recent years. In this review, we address the role of Lpp in signaling and modulating the immune response, in inflammation, and in pathogenicity. We also address the potential of Lpp as promising vaccine candidates.
Simulation and projection of climatic changes in the Indus River Basin, using the regional climate model COSMO‐CLM
2016-08-11

ABSTRACT In this article, the analysis of simulated and projected climatic changes in the Indus River Basin ( IRB ) is presented. The performance of the regional climate model COSMO‐CLM ( CCLM ) driven by the global circulation model MPI‐ESM‐LR is evaluated on the ability of reproducing temperature, precipitation, and wind pattern for the period 1961–2005. There exist quantitative biases, especially in precipitation pattern, which are associated to the diverse reproduction of the atmospheric circulation by the global circulation model. The overall results show that CCLM is able to satisfyingly capture the dominant spatial characteristics in annual temperature and precipitation time series, including the warming trend, and the seasonal variations. The changes in precipitation and temperature over the IRB are projected for the mid‐ (2046–2065) and late‐21st century (2081–2100). Relative to the baseline period (1986–2005), the average annual temperature will increase during the mid‐ and late‐21st century over the whole basin. Extreme temperature events, i.e. heat waves, are more likely to occur. An increase in summer temperature is also projected especially in the upper IRB , where the persistent increase is likely to cause further melting of glaciers. The annual precipitation will decrease in both the mid‐ and late‐21st century with significant spatial changes. A decrease in the monsoon precipitation is also projected, particularly in the central and southern plains of lower altitudes, which might be highly related to the reduction of wet air from the Indian Ocean and the increment in outflow to the east of the IRB . For winter and spring precipitation, except for the late‐21st century under the representative climate pathway (RCP) 2.6, a decreasing trend is projected, which might be caused by the reduction of water vapour from the west. This will further weaken the availability of water resources in these seasons, especially in the upper IRB of higher altitudes.