julilili42/papers huggingface dataset:
Nuclear delivery of recombinant OCT4 by chitosan nanoparticles for transgene-free generation of protein-induced pluripotent stem cells
2016-05-10

Protein-based reprogramming of somatic cells is a non-genetic approach for the generation of induced pluripotent stem cells (iPSCs), whereby reprogramming factors, such as OCT4, SOX2, KLF4 and c-MYC, are delivered as functional proteins. The technique is considered safer than transgenic methods, but, unfortunately, most protein-based protocols provide very low reprogramming efficiencies. In this study, we developed exemplarily a nanoparticle (NP)-based delivery system for the reprogramming factor OCT4. To this end, we expressed human OCT4 in Sf9 insect cells using a baculoviral expression system. Recombinant OCT4 showed nuclear localization in Sf9 cells indicating proper protein folding. In comparison to soluble OCT4 protein, encapsulation of OCT4 in nuclear-targeted chitosan NPs strongly stabilized its DNA-binding activity even under cell culture conditions. OCT4-loaded NPs enabled cell treatment with high micromolar concentrations of OCT4 and successfully delivered active OCT4 into human fibroblasts. Chitosan NPs therefore provide a promising tool for the generation of transgene-free iPSCs.
Broadband observations of the X-ray burster 4U1705-44 withBeppoSAX
2016-05-10

4U 1705-44 is one of the most-studied type I X-ray burster and Atoll sources. This source represents a perfect candidate to test different models proposed to self-consistently track the physical changes occurring between different spectral states because it shows clear spectral state transitions. The broadband coverage, the sensitivity and energy resolution of the BeppoSAX satellite offers the opportunity to disentangle the components that form the total X-ray spectrum and to study their changes according to the spectral state. Using two BeppoSAX observations carried out in August and October 2000, respectively, for a total effective exposure time of about 100 ks, we study the spectral evolution of the source from a soft to hard state. Energy spectra are selected according to the source position in the color-color diagram (CCD) Results. We succeeded in modeling the spectra of the source using a physical self-consistent scenario for both the island and banana branches (the double Comptonization scenario). The components observed are the soft Comptonization and hard Comptonization, the blackbody, and a reflection component with a broad iron line. When the source moves from the banana state to the island state, the parameters of the two Comptonization components change significantly and the blackbody component becomes too weak to be detected. We interpret the soft Comptonization component as emission from the hot plasma surrounding the neutron star, hard Comptonization as emission from the disk region, and the blackbody component as emission from the inner accretion disk. The broad feature in the iron line region is compatible with reflection from the inner accretion disk.
Taxonomic revision of the fossil generaBulimactaeon,Hemiauricula(=Liocarenus) andNucleopsis, with description of a new Recent genus and species (Gastropoda: Heterobranchia: Acteonidae)
2016-05-10

The genus &lt;it&gt;Liocarenus&lt;/it&gt; (Acteonidae) was originally described from Eocene fossil material and has subsequently come to include three subgenera (&lt;it&gt;Liocarenus s. s&lt;/it&gt;., &lt;it&gt;Bulimactaeon&lt;/it&gt; and &lt;it&gt;Nucleopsis&lt;/it&gt;) and nine species, including a Recent one (&lt;it&gt;L. globulinus&lt;/it&gt;). Together, these have been accorded status as a subfamily, Liocareninae. We here present a taxonomic revision of all the species and subgenera historically ascribed to &lt;it&gt;Liocarenus&lt;/it&gt;. We show that the genus name &lt;it&gt;Liocarenus&lt;/it&gt; is an objective synonym of &lt;it&gt;Hemiauricula&lt;/it&gt;. All three taxa (&lt;it&gt;Bulimactaeon&lt;/it&gt;, &lt;it&gt;Hemiauricula&lt;/it&gt; and &lt;it&gt;Nucleopsis&lt;/it&gt;) are accepted at genus level and a new genus, &lt;it&gt;Rapturella&lt;/it&gt;, is erected for the Recent species. &lt;it&gt;Rapturella&lt;/it&gt; is diagnosed by a thick shell with rounded whorls, slightly stepped spire, two closely spaced subsutural spiral grooves, a weak columellar fold and a tooth-like palatal thickening. Three of the formerly included species of &lt;it&gt;Liocarenus&lt;/it&gt; are here excluded from the Acteonidae. The revised classification is as follows: &lt;it&gt;B. bernayi&lt;/it&gt; (Cossmann, 1892), &lt;it&gt;H. edentula&lt;/it&gt; (F&lt;a&gt;&lt;ac&gt;e&lt;/ac&gt;&lt;ac&gt; ́&lt;/ac&gt;&lt;/a&gt;russac, 1821), &lt;it&gt;H. hilarionis&lt;/it&gt; (Bayan, 1870) n. comb., &lt;it&gt;N. subvaricatus&lt;/it&gt; (Conrad, 1860), &lt;it&gt;R. globulina&lt;/it&gt; (Forbes, 1844) n. comb. and &lt;it&gt;R. ryani&lt;/it&gt; n. sp. (Acteonidae); &lt;it&gt;Hamlinia eliai&lt;/it&gt; (Shalem, 1928) n. comb. and &lt;it&gt;Globiconcha formosa&lt;/it&gt; (Cragin, 1893) n. comb. (Cylindrobullinidae); &lt;it&gt;Ringicula lata&lt;/it&gt; (Conrad, 1865) n. comb. (Ringiculidae). &lt;it&gt;Acteon costellatus&lt;/it&gt; Conrad, 1833 is considered a &lt;it&gt;species inquirenda&lt;/it&gt;.
Regionalization of surface lipids in insects
2016-05-11

Cuticular hydrocarbons (CHCs) play a critical role in the establishment of the waterproof barrier that prevents dehydration and wetting in insects. While rich data are available on CHC composition in different species, we know little about their distribution and organization. Here, we report on our studies of the surface barrier of the fruit fly Drosophila melanogaster applying a newly developed Eosin Y staining method. The inert Eosin Y penetrates different regions of the adult body at distinct temperatures. By contrast, the larval body takes up the dye rather uniformly and gradually with increasing temperature. Cooling down specimens to 25°C after incubation at higher temperatures restores impermeability. Eosin Y penetration is also sensitive to lipid solvents such as chloroform indicating that permeability depends on CHCs. As in D. melanogaster adult flies, Eosin Y penetration is regionalized in Tenebrio molitor larvae, whereas it is not in Locusta migratoria nymphs. Regionalization of the fly surface implies tissue-specific variation of the genetic or biochemical programmes of CHC production and deposition. The Eosin Y-based map of CHC distribution may serve to identify the respective factors that are activated to accommodate ecological needs.
Peripheral Immune Signatures in Alzheimer Disease
2016-05-11

According to the current paradigm, the main cause of AD is the accumulation of neurotoxic amyloid beta (Aβ) peptide aggregates resulting from the cleavage of the amyloid precursor protein into peptides of different length, with the 42 amino acid long Aβ42 being the most toxic form. Aβ can aggregate and form plaques in the brain. It further promotes the hyperphosphorylation of the tau protein which forms characteristic neurofibrillary tangles and thereby loses its important role in axonal transport and contributes to neurodegeneration. Therefore, treatments have targeted Aβ, but clinical trials of immunotherapies caused severe side effects and showed that Aβ clearance alone did not result in any cognitive improvement. This leads to the question: what else promotes AD pathology? Here, we review data on systemic inflammation and the possible roles that the immune system might play in AD. Microglia and astrocytes are activated and secrete inflammatory cytokines and chemokines. Via a disturbed blood-brain barrier, peripheral immune cells are activated and recruited towards inflamed brain lesions and amyloid plaques, but due to the chronic nature of the amyloid burden and their reduced function, these cells are not able to control inflammation and the associated detrimental immune responses. In addition, age-related inflammation and chronic infection with herpes viruses might contribute to the systemic inflammation and exacerbate attempts to restore the balance of inflammation.
Impact of iterative metal artifact reduction on diagnostic image quality in patients with dental hardware
2016-05-11

Background Metal artifacts often impair diagnostic accuracy in computed tomography (CT) imaging. Therefore, effective and workflow implemented metal artifact reduction algorithms are crucial to gain higher diagnostic image quality in patients with metallic hardware. Purpose To assess the clinical performance of a novel iterative metal artifact reduction (iMAR) algorithm for CT in patients with dental fillings. Material and Methods Thirty consecutive patients scheduled for CT imaging and dental fillings were included in the analysis. All patients underwent CT imaging using a second generation dual-source CT scanner (120 kV single-energy; 100/Sn140 kV in dual-energy, 219 mAs, gantry rotation time 0.28–1/s, collimation 0.6 mm) as part of their clinical work-up. Post-processing included standard kernel (B49) and an iterative MAR algorithm. Image quality and diagnostic value were assessed qualitatively (Likert scale) and quantitatively (HU ± SD) by two reviewers independently. Results All 30 patients were included in the analysis, with equal reconstruction times for iMAR and standard reconstruction (17 s ± 0.5 vs. 19 s ± 0.5; P &gt; 0.05). Visual image quality was significantly higher for iMAR as compared with standard reconstruction (3.8 ± 0.5 vs. 2.6 ± 0.5; P &lt; 0.0001, respectively) and showed improved evaluation of adjacent anatomical structures. Similarly, HU-based measurements of degree of artifacts were significantly lower in the iMAR reconstructions as compared with the standard reconstruction (0.9 ± 1.6 vs. –20 ± 47; P &lt; 0.05, respectively). Conclusion The tested iterative, raw-data based reconstruction MAR algorithm allows for a significant reduction of metal artifacts and improved evaluation of adjacent anatomical structures in the head and neck area in patients with dental hardware.
Aus heiterem Himmel? – Zur Problematik der zeitlichen Einordnung der Sūrat al-Fātiḥa, Sūrat al-Kawṯar und Sūrat al-Iḫlāṣ
2016-05-11

Both in classical Qurʾānic exegesis and in Islamic, i.e. Orientalist, studies the dating – distinguishing strictly between either Meccan or Medinan origin – and interpretation of Sūrat al-Fātiḥa, Sūrat al-Kawṯar and Sūrat al-Iḫlāṣ has excited much controversy amongst scholars of both disciplines alike. Faced with diverging contexts of emergence, scholars of Qurʾānic tafsīr attempted to tackle the difficulties in classifying and interpreting ambiguously dated surahs by formulating patterns of explanation, suggesting, amongst other things, the repeated revelation of certain surahs or their bipartite structure. On the other hand, Orientalists employing the historical-critical method of interpretation sought to categorise and interpret the surahs according to their historical, literary-critical, phenomenological and content-related characteristics. However, both methods have failed to provide a distinct, unambiguous classification into either the Meccan or Medinan context. In their article, authors Omar Hamdan and Patrick Brooks override the maxims of dating a surah chronologically and allocating to it a concrete worldly occasion for its revelation by considering an alternative circumstance of revelation. Drawing on the sacred texts of Islam and byoutlining the thematic connections between the surahs, the authors place these into the joint context of the Prophet’s night journey of ascension (laylat al-miʿrāğ), thus dating them into the late Meccan period. In doing so, they identify not a worldly, but heavenly – and therefore timeless – occasion of revelation.
Increases in Absolute Lymphocytes and Circulating CD4+ and CD8+ T Cells Are Associated with Positive Clinical Outcome of Melanoma Patients Treated with Ipilimumab
2016-05-12

Abstract Purpose: To investigate changes of peripheral blood biomarkers and their impact on clinical outcome following treatment with ipilimumab in advanced melanoma patients. Experimental Design: Changes in blood counts and the frequency of circulating immune cell populations analyzed by flow cytometry were investigated in 82 patients to compare baseline values with different time-points after starting ipilimumab. Endpoints were overall survival (OS) and best clinical response. Statistical calculations were done by Wilcoxon-matched pairs tests, Fisher exact test, Kaplan–Meier analysis, and Cox regression analysis. Results: Increases in absolute lymphocyte counts (ALC) 2 to 8 weeks (P = 0.003) and in percentages of CD4+ and CD8+ T cells 8 to 14 weeks (P = 0.001 and P = 0.02) after the first dose of ipilimumab were correlated with improved survival. These associations did not meet significance criteria, when conservatively adjusted for multiple testing, but were additionally correlated with clinical responses (all P &amp;lt; 0.05). However, validation is required. Increases in all three factors were observed in 36% of patients, who had a favorable outcome and survival probabilities of 93.3% and 63.8% at 12 and 24 months, respectively. A partial or complete response was observed in 71% of these patients compared with only 8% in patients with decreases in ≥1 of the 3 factors, respectively. Changes of regulatory T cells or myeloid-derived suppressor cells were not associated with OS. Conclusions: Increases of ALC observed 2 to 8 weeks after initiation of ipilimumab and delayed increases in CD4+ and CD8+ T cells reflect changes associated with positive outcome. These changes represent surrogate marker candidates and warrant further validation. Clin Cancer Res; 22(19); 4848–58. ©2016 AACR.
Epitaxial Growth of an Organic p–n Heterojunction: C60 on Single-Crystal Pentacene
2016-05-12

Designing molecular p-n heterojunction structures, i.e., electron donor-acceptor contacts, is one of the central challenges for further development of organic electronic devices. In the present study, a well-defined p-n heterojunction of two representative molecular semiconductors, pentacene and C60, formed on the single-crystal surface of pentacene is precisely investigated in terms of its growth behavior and crystallographic structure. C60 assembles into a (111)-oriented face-centered-cubic crystal structure with a specific epitaxial orientation on the (001) surface of the pentacene single crystal. The present experimental findings provide molecular scale insights into the formation mechanisms of the organic p-n heterojunction through an accurate structural analysis of the single-crystalline molecular contact.
Evolutionary potential in the Alpine: trait heritabilities and performance variation of the dwarf willow Salix herbacea from different elevations and microhabitats
2016-05-12

Abstract Alpine ecosystems are seriously threatened by climate change. One of the key mechanisms by which plants can adapt to changing environmental conditions is through evolutionary change. However, we still know little about the evolutionary potential in wild populations of long‐lived alpine plants. Here, we investigated heritabilities of phenological traits, leaf size, and performance traits in natural populations of the long‐lived alpine dwarf shrub Salix herbacea using relatedness estimates inferred from SSR (Simple Sequence Repeat) markers. Salix herbacea occurs in early‐ and late‐snowmelt microhabitats (ridges and snowbeds), and we assessed how performance consequences of phenological traits and leaf size differ between these microhabitats in order to infer potential for evolutionary responses. Salix herbacea showed low, but significant, heritabilities of leaf size, clonal and sexual reproduction, and moderate heritabilities of phenological traits. In both microhabitats, we found that larger leaves, longer intervals between snowmelt and leaf expansion, and longer GDD (growing‐degree days) until leaf expansion resulted in a stronger increase in the number of stems (clonal reproduction). In snowbeds, clonal reproduction increased with a shorter GDD until flowering, while the opposite was found on ridges. Furthermore, the proportion of flowering stems increased with GDD until flowering in both microhabitats. Our results suggest that the presence of significant heritable variation in morphology and phenology might help S. herbacea to adapt to changing environmental conditions. However, it remains to be seen if the rate of such an evolutionary response can keep pace with the rapid rate of climate change.
New insights in the systemic and molecular underpinnings of general anesthetic actions mediated by γ-aminobutyric acid A receptors
2016-05-12

Identification of the molecular and cellular substrates involved in anesthesia and insights into disease and drug-induced alterations in the expression patterns of GABAA receptors in the central nervous system are emphasizing the need for individualized anesthesia care. Introducing neuroactive steroids into clinical anesthesia is expected to reduce cardiovascular and respiratory side-effects.
Phase retrapping in aφJosephson junction: Onset of the butterfly effect
2016-05-12

We investigate experimentally the retrapping of the phase in a &#13;\\nφ&#13;\\n Josephson junction upon return of the junction to the zero-voltage state. Since the Josephson energy profile &#13;\\nU&#13;\\n0&#13;\\n(&#13;\\nψ&#13;\\n)&#13;\\n in &#13;\\nφ&#13;\\n JJ is a &#13;\\n2&#13;\\nπ&#13;\\n periodic double-well potential with minima at &#13;\\nψ&#13;\\n=&#13;\\n±&#13;\\nφ&#13;\\nmod&#13;\\n2&#13;\\nπ&#13;\\n, the question is at which of the two minima &#13;\\n−&#13;\\nφ&#13;\\nor &#13;\\n+&#13;\\nφ&#13;\\n the phase will be trapped upon return from a finite voltage state during quasistatic decrease of the bias current (tilt of the potential). By measuring the relative population of two peaks in escape histograms, we determine the probability of phase trapping in the &#13;\\n±&#13;\\nφ&#13;\\n wells for different temperatures. Our experimental results agree qualitatively with theoretical predictions. In particular, we observe an onset of the butterfly effect with an oscillating probability of trapping. Unexpectedly, this probability saturates at a value different from 50% at low temperatures.
Muon capture on light isotopes measured with the Double Chooz detector
2016-05-12

Using the Double Chooz detector, designed to measure the neutrino mixing angle θ13, the products of μ- capture on C12,C13,N14, and O16 have been measured. Over a period of 489.5 days, 2.3×106 stopping cosmic μ- have been collected, of which 1.8×105 captured on carbon, nitrogen, or oxygen nuclei in the inner detector scintillator or acrylic vessels. The resulting isotopes were tagged using prompt neutron emission (when applicable), the subsequent β decays, and, in some cases, β-delayed neutrons. The most precise measurement of the rate of C12(μ-,ν)B12 to date is reported: 6.57-0.21+0.11×103s-1, or (17.35-0.59+0.35)% of nuclear captures. By tagging excited states emitting γs, the ground state transition rate to B12 has been determined to be 5.68-0.23+0.14×103s-1. The heretofore unobserved reactions C12(μ-,να)Li8,C13(μ-,νnα)Li8, and C13(μ-,νn)B12 are measured. Further, a population of βn decays following stopping muons is identified with 5.5σ significance. Statistics limit our ability to identify these decays definitively. Assuming negligible production of He8, the reaction C13(μ-,να)Li9 is found to be present at the 2.7σ level. Limits are set on a variety of other processes.
The Influence of Methylphenidate on Hyperactivity and Attention Deficits in Children With ADHD: A Virtual Classroom Test
2016-05-13

Objective: This study compares the performance in a continuous performance test within a virtual reality classroom (CPT-VRC) between medicated children with ADHD, unmedicated children with ADHD, and healthy children. Method: N = 94 children with ADHD ( n = 26 of them received methylphenidate and n = 68 were unmedicated) and n = 34 healthy children performed the CPT-VRC. Omission errors, reaction time/variability, commission errors, and body movements were assessed. Furthermore, ADHD questionnaires were administered and compared with the CPT-VRC measures. Results: The unmedicated ADHD group exhibited more omission errors and showed slower reaction times than the healthy group. Reaction time variability was higher in the unmedicated ADHD group compared with both the healthy and the medicated ADHD group. Omission errors and reaction time variability were associated with inattentiveness ratings of experimenters. Head movements were correlated with hyperactivity ratings of parents and experimenters. Conclusion: Virtual reality is a promising technology to assess ADHD symptoms in an ecologically valid environment.
Learning from Heterogeneous Data Sources: An Application in Spatial Proteomics
2016-05-13

Sub-cellular localisation of proteins is an essential post-translational regulatory mechanism that can be assayed using high-throughput mass spectrometry (MS). These MS-based spatial proteomics experiments enable us to pinpoint the sub-cellular distribution of thousands of proteins in a specific system under controlled conditions. Recent advances in high-throughput MS methods have yielded a plethora of experimental spatial proteomics data for the cell biology community. Yet, there are many third-party data sources, such as immunofluorescence microscopy or protein annotations and sequences, which represent a rich and vast source of complementary information. We present a unique transfer learning classification framework that utilises a nearest-neighbour or support vector machine system, to integrate heterogeneous data sources to considerably improve on the quantity and quality of sub-cellular protein assignment. We demonstrate the utility of our algorithms through evaluation of five experimental datasets, from four different species in conjunction with four different auxiliary data sources to classify proteins to tens of sub-cellular compartments with high generalisation accuracy. We further apply the method to an experiment on pluripotent mouse embryonic stem cells to classify a set of previously unknown proteins, and validate our findings against a recent high resolution map of the mouse stem cell proteome. The methodology is distributed as part of the open-source Bioconductor pRoloc suite for spatial proteomics data analysis.
Maternal eNOS deficiency determines a fatty liver phenotype of the offspring in a sex dependent manner
2016-05-13

Maternal environmental factors can impact on the phenotype of the offspring via the induction of epigenetic adaptive mechanisms. The advanced fetal programming hypothesis proposes that maternal genetic variants may influence the offspring's phenotype indirectly via epigenetic modification, despite the absence of a primary genetic defect. To test this hypothesis, heterozygous female eNOS knockout mice and wild type mice were bred with male wild type mice. We then assessed the impact of maternal eNOS deficiency on the liver phenotype of wild type offspring. Birth weight of male wild type offspring born to female heterozygous eNOS knockout mice was reduced compared to offspring of wild type mice. Moreover, the offspring displayed a sex specific liver phenotype, with an increased liver weight, due to steatosis. This was accompanied by sex specific differences in expression and DNA methylation of distinct genes. Liver global DNA methylation was significantly enhanced in both male and female offspring. Also, hepatic parameters of carbohydrate metabolism were reduced in male and female offspring. In addition, male mice displayed reductions in various amino acids in the liver. Maternal genetic alterations, such as partial deletion of the eNOS gene, can affect liver metabolism of wild type offspring without transmission of the intrinsic defect. This occurs in a sex specific way, with more detrimental effects in females. This finding demonstrates that a maternal genetic defect can epigenetically alter the phenotype of the offspring, without inheritance of the defect itself. Importantly, these acquired epigenetic phenotypic changes can persist into adulthood.