julilili42/papers huggingface dataset:
Broadband electron spin resonance from 500 MHz to 40 GHz using superconducting coplanar waveguides
2013-04-22

We present non-conventional electron spin resonance (ESR) experiments based on microfabricated superconducting Nb thin film waveguides. A very broad frequency range, from 0.5 to 40 GHz, becomes accessible at low temperatures down to 1.6 K and in magnetic fields up to 1.4 T. This allows for an accurate inspection of the ESR absorption position in the frequency domain, in contrast to the more common observation as a function of magnetic field. We demonstrate the applicability of frequency-swept ESR on Cr3+ atoms in ruby as well as on organic radicals of the nitronyl-nitroxide family. Measurements between 1.6 and 30 K reveal a small frequency shift of the ESR and a resonance broadening below the critical temperature of Nb, which we both attribute to a modification of the magnetic field configuration due to the appearance of shielding supercurrents in the waveguide.
The potential of operando XAFS for determining the role and structure of noble metal additives in metal oxide based gas sensors
2013-04-22

Noble metal additives significantly improve the performance of SnO2 based sensors. Recently, it has been found that X-ray absorption spectroscopy is an excellent tool to identify their structure under sensing conditions, despite of the low concentrations and the rather thin (50 μm) and highly porous layers. For this purpose a new in situ approach has been established and here we highlight the potential with an overview on the results of Pd-, Pt-, and Au-additives in SnO2-based sensors at work. Emphasis was laid on recording the structure (by XANES and EXAFS) and performance at the same time. In contrast to earlier studies, Pd- and Pt-additives were observed to be in oxidized and finely dispersed state under sensing conditions excluding a spillover from metallic noble metal particles. However, Au was mainly present as metallic particles in the sensing SnO2-layer. For the Pt- and Au-doped SnO2-layers high energy-resolved fluorescence detected X-ray absorption spectra (HERFD-XAS) were recorded not only to minimize the lifetime-broadening but also to eliminate the Au- and Pt-fluorescence effectively and to record range-extended EXAFS.
Kant on Virtue
2013-04-22

In business ethics journals, Kant's ethics is often portrayed as overly formalistic, devoid of substantial content, and without regard for the consequences of actions or questions of character. Hence virtue ethicists ride happily to the rescue, offering to replace or complement Kant's theory with theirs. Before such efforts are undertaken, however, one should recognize that Kant himself wrote a 'virtue theory' (Tugendlehre), wherein he discussed the questions of character as well as the teleological nature of human action. Numerous Kant scholars argue that Kant already erected precisely the kind of integrative moral architecture that some of his modern interpreters (while aiming to supersede him) wish to construct. For business ethics, this divergence of scholarly opinion is of crucial importance. It shows first that the standard textbook portrayals of Kant's ethics – as rigidly deontological, narrowly individualistic, and hence unsuitable for the specific demands of corporate agency – might have to be revised. Second, discussions in academic literature on theories of stakeholder-engagement and managerial decision-making likewise stand to gain from a more nuanced picture of Kant's moral philosophy. Third, a reassessment of Kant's ethics in regard to questions of personal character and moral sentiments might also be warranted. Last, but not least, the many current attempts to reconcile Kant's freedom-oriented philosophy with virtue theories stand to benefit considerably from better understanding how Kant himself aimed at one such synthesis between the formal and substantial aspects of morality.
Faculty Opinions recommendation of Mutations of DEPDC5 cause autosomal dominant focal epilepsies.
2013-04-22

The main familial focal epilepsies are autosomal dominant nocturnal frontal lobe epilepsy, familial temporal lobe epilepsy and familial focal epilepsy with variable foci. A frameshift mutation in the DEPDC5 gene (encoding DEP domain-containing protein 5) was identified in a family with focal epilepsy with variable foci by linkage analysis and exome sequencing. Subsequent pyrosequencing of DEPDC5 in a cohort of 15 additional families with focal epilepsies identified 4 nonsense mutations and 1 missense mutation. Our findings provided evidence of frequent (37%) loss-of-function mutations in DEPDC5 associated with a broad spectrum of focal epilepsies. The implication of a DEP (Dishevelled, Egl-10 and Pleckstrin) domain-containing protein that may be involved in membrane trafficking and/or G protein signaling opens new avenues for research. PMID: 23542701 Funding information This work was supported by: European Research Council, International Grant ID: 322721
Mitogen-Activated Protein Kinase-Activated Protein Kinases 2 and 3 Regulate SERCA2a Expression and Fiber Type Composition To Modulate Skeletal Muscle and Cardiomyocyte Function
2013-04-23

The mitogen-activated protein kinase (MAPK)-activated protein kinases 2 and 3 (MK2/3) represent protein kinases downstream of the p38 MAPK. Using MK2/3 double-knockout (MK2/3(-/-)) mice, we analyzed the role of MK2/3 in cross-striated muscle by transcriptome and proteome analyses and by histology. We demonstrated enhanced expression of the slow oxidative skeletal muscle myofiber gene program, including the peroxisome proliferator-activated receptor gamma (PPARγ) coactivator 1α (PGC-1α). Using reporter gene and electrophoretic gel mobility shift assays, we demonstrated that MK2 catalytic activity directly regulated the promoters of the fast fiber-specific myosin heavy-chain IId/x and the slow fiber-specific sarco/endoplasmic reticulum Ca(2+)-ATPase 2 (SERCA2) gene. Elevated SERCA2a gene expression caused by a decreased ratio of transcription factor Egr-1 to Sp1 was associated with accelerated relaxation and enhanced contractility in MK2/3(-/-) cardiomyocytes, concomitant with improved force parameters in MK2/3(-/-) soleus muscle. These results link MK2/3 to the regulation of calcium dynamics and identify enzymatic activity of MK2/3 as a critical factor for modulating cross-striated muscle function by generating a unique muscle phenotype exhibiting both reduced fatigability and enhanced force in MK2/3(-/-) mice. Hence, the p38-MK2/3 axis may represent a novel target for the design of therapeutic strategies for diseases related to fiber type changes or impaired SERCA2 function.
Is there a relationship between fetal brain function and the fetal behavioral state? A fetal MEG-study
2013-04-23

Abstract Aim: Fetal magnetography enables the recording of biomagnetic fetal signals, including fetal heart and fetal brain signals. These signals allow the determination of fetal behavioral states and functional brain signals with auditory evoked responses (AER). In the current study, we investigated how the behavioral state influences the AER and how stimulation affects fetal state. Methods: One hundred and four fetuses in three age groups (28–31 weeks, 32–35 weeks and 36–41 weeks) were recorded with and without auditory stimulation. Both sessions were scored for fetal states. The AER latency was determined for each state separately. Forty-five additional subjects were recorded with two sessions of 10 min without stimulation to investigate a possible time effect on state changes. Results: The state distribution was significantly different between stimulation and no stimulation conditions. The AER latencies were significantly shorter in active sleep (P=0.013) and active wakefulness (P=0.004) compared to quiet sleep. Conclusion: Auditory stimulation has an effect on fetal states. The state information should be taken into account for the analysis of AER latencies.
Cerebellar Soluble Mutant Ataxin-3 Level Decreases during Disease Progression in Spinocerebellar Ataxia Type 3 Mice
2013-04-23

Spinocerebellar Ataxia Type 3 (SCA3), also known as Machado-Joseph disease, is an autosomal dominantly inherited neurodegenerative disease caused by an expanded polyglutamine stretch in the ataxin-3 protein. A pathological hallmark of the disease is cerebellar and brainstem atrophy, which correlates with the formation of intranuclear aggregates in a specific subset of neurons. Several studies have demonstrated that the formation of aggregates depends on the generation of aggregation-prone and toxic intracellular ataxin-3 fragments after proteolytic cleavage of the full-length protein. Despite this observed increase in aggregated mutant ataxin-3, information on soluble mutant ataxin-3 levels in brain tissue is lacking. A quantitative method to analyze soluble levels will be a useful tool to characterize disease progression or to screen and identify therapeutic compounds modulating the level of toxic soluble ataxin-3. In the present study we describe the development and application of a quantitative and easily applicable immunoassay for quantification of soluble mutant ataxin-3 in human cell lines and brain samples of transgenic SCA3 mice. Consistent with observations in Huntington disease, transgenic SCA3 mice reveal a tendency for decrease of soluble mutant ataxin-3 during disease progression in fractions of the cerebellum, which is inversely correlated with aggregate formation and phenotypic aggravation. Our analyses demonstrate that the time-resolved Förster resonance energy transfer immunoassay is a highly sensitive and easy method to measure the level of soluble mutant ataxin-3 in biological samples. Of interest, we observed a tendency for decrease of soluble mutant ataxin-3 only in the cerebellum of transgenic SCA3 mice, one of the most affected brain regions in Spinocerebellar Ataxia Type 3 but not in whole brain tissue, indicative of a brain region selective change in mutant ataxin-3 protein homeostasis.
12q24.33 deletion: Report of a patient with intellectual disability and review of the literature
2013-04-23

Abstract Deletions of chromosome band 12q24.33 are rare. We report on a 17‐year‐old male patient with intellectual disability but no major malformations or dysmorphic features in whom a de novo interstitial 660 kb deletion in 12q24.33 was detected by SNP array analysis. This deletion was secondary to a translocation t(12;14)(q24.3;q13)dn that also led to a small deletion in 14q21.1 and a small duplication in 2p23.1. The deletion overlaps with two previously published larger deletions in patients who suffered from intellectual disability, obesity, and polycystic kidney disease, indicating that haploinsufficiency of one or several of the genes in the deleted interval of the patient reported here causes intellectual deficits, but not obesity or renal problems. The 14 RefSeq genes that are harbored by this deletion include P2RX2 , which had previously been proposed as a candidate gene for intellectual disability. Thus, the patient reported here broadens our knowledge of the phenotypic consequences of deletions in 12q24.33 and facilitates genotype–phenotype correlations for chromosome aberrations of this region. © 2013 Wiley Periodicals, Inc.
Representation of Abstract Quantitative Rules Applied to Spatial and Numerical Magnitudes in Primate Prefrontal Cortex
2013-04-24

Processing quantity information based on abstract principles is central to intelligent behavior. Neural correlates of quantitative rule selectivity have been identified previously in the prefrontal cortex (PFC). However, whether individual neurons represent rules applied to multiple magnitude types is unknown. We recorded from PFC neurons while monkeys switched between “greater than/less than” rules applied to spatial and numerical magnitudes. A majority of rule-selective neurons responded only to the quantitative rules applied to one specific magnitude type. However, another population of neurons generalized the magnitude principle and represented the quantitative rules related to both magnitudes. This indicates that the primate brain uses rule-selective neurons specialized in guiding decisions related to a specific magnitude type only, as well as generalizing neurons that respond abstractly to the overarching concept “magnitude rules.”
A Novel Flow Cytometric Hemozoin Detection Assay for Real-Time Sensitivity Testing of Plasmodium falciparum
2013-04-24

Resistance of Plasmodium falciparum to almost all antimalarial drugs, including the first-line treatment with artemisinins, has been described, representing an obvious threat to malaria control. In vitro antimalarial sensitivity testing is crucial to detect and monitor drug resistance. Current assays have been successfully used to detect drug effects on parasites. However, they have some limitations, such as the use of radioactive or expensive reagents or long incubation times. Here we describe a novel assay to detect antimalarial drug effects, based on flow cytometric detection of hemozoin (Hz), which is rapid and does not require any additional reagents. Hz is an optimal parasite maturation indicator since its amount increases as the parasite matures. Due to its physical property of birefringence, Hz depolarizes light, hence it can be detected using optical methods such as flow cytometry. A common flow cytometer was adapted to detect light depolarization caused by Hz. Synchronized in vitro cultures of P. falciparum were incubated for 48 hours with several antimalarial drugs. Analysis of depolarizing events, corresponding to parasitized red blood cells containing Hz, allowed the detection of parasite maturation. Moreover, chloroquine resistance and the inhibitory effect of all antimalarial drugs tested, except for pyrimethamine, could be determined as early as 18 to 24 hours of incubation. At 24 hours incubation, 50% inhibitory concentrations (IC50) were comparable to previously reported values. These results indicate that the reagent-free, real-time Hz detection assay could become a novel assay for the detection of drug effects on Plasmodium falciparum.
Power and temptation cause shifts between exploitation and cooperation in a cleaner wrasse mutualism
2013-04-24

In many instances of cooperation, only one individual has both the potential and the incentive to ‘cheat’ and exploit its partner. Under these asymmetric conditions, a simple model predicts that variation in the temptation to cheat and in the potential victim's capacity for partner control leads to shifts between exploitation and cooperation. Here, we show that the threat of early termination of an interaction was sufficient to induce cleaner wrasse Labroides dimidiatus to feed selectively against their preference (which corresponds to cooperatively eating client fish ectoparasites), provided that their preference for alternative food was weak. Under opposite conditions, cleaners fed selectively according to their own preference (which corresponds to cheating by eating client mucus). By contrast, a non-cleaning fish species, Halichoeres melanurus , failed to adjust its foraging behaviour under these same conditions. Thus, cleaners appear to have evolved the power to strategically adjust their levels of cooperation according to the circumstances.
Seeking a Sex‐Specific Coolidge Effect in a Simultaneous Hermaphrodite
2013-04-24

Abstract In polygamous mating systems, a capability to discriminate against familiar mates may be beneficial to both sexes. Polyandrous females, for instance, may enhance the odds of finding sires with optimal genetic compatibility or high genetic quality by mating with multiple different males; polygynous males, in addition, may more efficiently invest their limited ejaculates across multiple (rather than single) females. The Coolidge effect facilitates this kind of mate discrimination, as sexual motivation declines across consecutive copulations with a familiar partner but resurrects with a novel mate. In simultaneous hermaphrodites, we expect the Coolidge effect to show sex role‐dependent patterns and vary with previous sex‐specific mating activity. Using the promiscuous hermaphroditic sea slug Chelidonura sandrana, we investigated (1) whether sexual motivation indeed declines when repeatedly exposed to familiar partners, (2) whether the Coolidge effect occurs in a sex‐specific manner and (3) whether ejaculation is strategic with respect to partner familiarity. We found neither mating latency, nor penis intromission duration, mating propensity or the frequency of sex role alternations to vary significantly with treatments. Furthermore, slugs did not donate larger ejaculates to novel than to familiar partners. Partner novelty thus elicited no detectable response in sexual motivation or mating effort in C. sandrana . We suggest that the sea slugs' promiscuous mating system in often large mating aggregations makes mate discrimination based on novelty obsolete in comparison with more relevant criteria such as partner body size or mating history.
Common Genetic Variation in the Human FNDC5 Locus, Encoding the Novel Muscle-Derived ‘Browning’ Factor Irisin, Determines Insulin Sensitivity
2013-04-25

This study provides evidence that the FNDC5 gene, encoding the novel myokine irisin, determines insulin sensitivity in humans. Our gene expression data point to an unexpected insulin-desensitizing effect of irisin.
Acute effects of short‐chain alkylglycerols on blood‐brain barrier properties of cultured brain endothelial cells
2013-04-25

Background and Purpose The blood‐brain barrier ( BBB ) restricts drug penetration to the brain preventing effective treatment of patients suffering from brain tumours. Intra‐arterial injection of short‐chain alkylglycerols ( AGs ) opens the BBB and increases delivery of molecules to rodent brain parenchyma in vivo . The mechanism underlying AG ‐mediated modification of BBB permeability is still unknown. Here, we have tested the effects of AGs on barrier properties of cultured brain microvascular endothelial cells. Experimental Approach The effects of two AGs, 1‐ O ‐pentylglycerol and 2‐ O ‐hexyldiglycerol were examined using an in vitro BBB model consisting of primary cultures of rat brain endothelial cells, co‐cultured with rat cerebral glial cells. Integrity of the paracellular, tight junction‐based, permeation route was analysed by functional assays, immunostaining for junctional proteins, freeze‐fracture electron microscopy, and analysis of claudin‐claudin trans ‐interactions. Key Results AG treatment (5 min) reversibly reduced transendothelial electrical resistance and increased BBB permeability for fluorescein accompanied by changes in cell morphology and immunostaining for claudin‐5 and β‐catenin. These short‐term changes were not accompanied by alterations of inter‐endothelial tight junction strand complexity or the trans ‐interaction of claudin‐5. Conclusion and Implications AG ‐mediated increase in brain endothelial paracellular permeability was short, reversible and did not affect tight junction strand complexity. Redistribution of junctional proteins and alterations in the cell shape indicate the involvement of the cytoskeleton in the action of AGs . These data confirm the results from in vivo studies in rodents characterizing AGs as adjuvants that transiently open the BBB .
Phosphorylation of Serine 1137/1138 of Mouse Insulin Receptor Substrate (IRS) 2 Regulates cAMP-dependent Binding to 14-3-3 Proteins and IRS2 Protein Degradation
2013-04-25

Insulin receptor substrate (IRS) 2 as intermediate docking platform transduces the insulin/IGF-1 (insulin like growth factor 1) signal to intracellular effector molecules that regulate glucose homeostasis, β-cell growth, and survival. Previously, IRS2 has been identified as a 14-3-3 interaction protein. 14-3-3 proteins can bind their target proteins via phosphorylated serine/threonine residues located within distinct motifs. In this study the binding of 14-3-3 to IRS2 upon stimulation with forskolin or the cAMP analog 8-(4-chlorophenylthio)-cAMP was demonstrated in HEK293 cells. Binding was reduced with PKA inhibitors H89 or Rp-8-Br-cAMPS. Phosphorylation of IRS2 on PKA consensus motifs was induced by forskolin and the PKA activator N(6)-Phe-cAMP and prevented by both PKA inhibitors. The amino acid region after position 952 on IRS2 was identified as the 14-3-3 binding region by GST-14-3-3 pulldown assays. Mass spectrometric analysis revealed serine 1137 and serine 1138 as cAMP-dependent, potential PKA phosphorylation sites. Mutation of serine 1137/1138 to alanine strongly reduced the cAMP-dependent 14-3-3 binding. Application of cycloheximide revealed that forskolin enhanced IRS2 protein stability in HEK293 cells stably expressing IRS2 as well as in primary hepatocytes. Stimulation with forskolin did not increase protein stability either in the presence of a 14-3-3 antagonist or in the double 1137/1138 alanine mutant. Thus the reduced IRS2 protein degradation was dependent on the interaction with 14-3-3 proteins and the presence of serine 1137/1138. We present serine 1137/1138 as novel cAMP-dependent phosphorylation sites on IRS2 and show their importance in 14-3-3 binding and IRS2 protein stability.
Brain communication in the locked-in state
2013-04-26

Patients in the completely locked-in state have no means of communication and they represent the target population for brain-computer interface research in the last 15 years. Although different paradigms have been tested and different physiological signals used, to date no sufficiently documented completely locked-in state patient was able to control a brain-computer interface over an extended time period. We introduce Pavlovian semantic conditioning to enable basic communication in completely locked-in state. This novel paradigm is based on semantic conditioning for online classification of neuroelectric or any other physiological signals to discriminate between covert (cognitive) 'yes' and 'no' responses. The paradigm comprised the presentation of affirmative and negative statements used as conditioned stimuli, while the unconditioned stimulus consisted of electrical stimulation of the skin paired with affirmative statements. Three patients with advanced amyotrophic lateral sclerosis participated over an extended time period, one of which was in a completely locked-in state, the other two in the locked-in state. The patients' level of vigilance was assessed through auditory oddball procedures to study the correlation between vigilance level and the classifier's performance. The average online classification accuracies of slow cortical components of electroencephalographic signals were around chance level for all the patients. The use of a non-linear classifier in the offline classification procedure resulted in a substantial improvement of the accuracy in one locked-in state patient achieving 70% correct classification. A reliable level of performance in the completely locked-in state patient was not achieved uniformly throughout the 37 sessions despite intact cognitive processing capacity, but in some sessions communication accuracies up to 70% were achieved. Paradigm modifications are proposed. Rapid drop of vigilance was detected suggesting attentional variations or variations of circadian period as important factors in brain-computer interface communication with locked-in state and completely locked-in state.