julilili42/papers huggingface dataset:
Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis – a phase I first-in-human study
2018-06-08

Abstract Background Nanoparticles hold considerable promise for aerosol-based intraperitoneal delivery in patients with carcinomatosis. Recently, results from preclinical and early clinical trials suggested that albumin-bound paclitaxel (ABP, AbraxaneTM) may result in superior efficacy in the treatment of peritoneal metastases (PM) compared to the standard solvent-based paclitaxel formulation (TaxolTM). Here, we propose a phase I study of pressurized intraperitoneal aerosol chemotherapy (PIPAC) using ABP in patients with upper Gastrointestinal, breast, or ovarian cancer. Methods Eligible patients with advanced, biopsy-proven PM from ovarian, breast, gastric, hepatobiliary, or pancreatic origin will undergo three PIPAC treatments using ABP with a 4-week interval. The dose of ABP will be escalated from 35 to 140 mg/m2 using a Bayesian approach until the maximally tolerated dose is determined. The primary end point is dose-limiting toxicity. Secondary analyses include surgical morbidity, non-access rate, pharmacokinetic and pharmacodynamic analyses, quality of life, and exploratory circulating biomarker analyses. Discussion ABP holds considerable promise for intraperitoneal aerosol delivery. The aim of this study is to determine the dose level for future randomized phase II trials using ABP in PIPAC therapy. Trial registration This trial is registered as EudraCT: 2017-001688-20 and Clinicaltrials.gov: NCT03304210.
Refining the Nonterminal Complexity of Graph-Controlled, Programmed, and Matrix Grammars
2018-06-08

We refine the classical notion of the nonterminal complexity of graph-controlled grammars, programmed grammars, and matrix grammars by also counting, in addition, the number of nonterminal symbols that are actually used in the appearance checking mode. We prove that every recursively enumerable language can be generated by a graph-controlled grammar with only two nonterminal symbols when both symbols are used in the appearance checking mode. This result immediately implies that programmed grammars with three nonterminal symbols where two of them are used in the appearance checking mode as well as matrix grammars with three nonterminal symbols all of them used in the appearance checking mode are computationally complete. Moreover, we prove that matrix grammars with four nonterminal symbols with only two of them being used in the appearance checking mode are computationally complete, too. On the other hand, every language is recursive if it is generated by a graphcontrolled grammar with an arbitrary number of nonterminal symbols but only one of the nonterminal symbols being allowed to be used in the appearance checking mode. This implies, in particular, that the result proving the computational completeness of graph-controlled grammars with two nonterminal symbols and both of them being used in the appearance checking mode is already optimal with respect to the overall number of nonterminal symbols as well as with respect to the number of nonterminal symbols used in the appearance checking mode, too. Finally, we also investigate in more detail the computational power of several language families which are generated by graph-controlled, programmed grammars or matrix grammars, respectively, with a very small number of nonterminal symbols and therefore are proper subfamilies of the family of recursively enumerable languages.
Tracing the developmental origin of a lizard skull: Chondrocranial architecture, heterochrony, and variation in lacertids
2018-06-08

Abstract The sand lizard, Lacerta agilis , is a classical model species in herpetology. Its adult skull anatomy and its embryonic development are well known. The description of its fully formed primordial skull by Ernst Gaupp, in 1900, was a key publication in vertebrate morphology and influenced many comparative embryologists. Based on recent methodological considerations, we restudied the early cranial development of this species starting as early as the formation of mesenchymal condensations up to the fully formed chondrocranium. We traced the formation of the complex chondrocranial architecture in detail, clarified specific homologies for the first time, and uncovered major differences to old textbook descriptions. Comparison with other lacertid lizards revealed a very similar genesis of the primordial skull. However, we detected shifts in the developmental timing of particular cartilaginous elements, mainly in the nasal region, which may correlate to specific ecological adaptation in the adults. Late timing of nasal elements might be an important innovation for the successful wide range distribution of the well‐known sand lizard.
GPT2 mutations cause developmental encephalopathy with microcephaly and features of complicated hereditary spastic paraplegia
2018-06-08

Various genetic defects can cause intellectual and developmental disabilities (IDDs). Often IDD is a symptom of a more complex neurodevelopmental or neurodegenerative syndrome. Identifying syndromic patterns is substantive for diagnostics and for understanding the pathomechanism of a disease. Recessive glutamate pyruvate transaminase (GPT2) mutations have recently been associated with IDD in 4 families. Here, we report a novel recessive GPT2 stop mutation p.Gln24* causing a complex IDD phenotype in a homozygous state in 5 patients from 2 consanguineous Arab families. By compiling clinical information of these individuals and previously described GPT2 patients a recognizable neurodevelopmental and potentially neurodegenerative phenotype can be assigned consisting of intellectual disability, pyramidal tract affection with spastic paraplegia, microcephaly and frequently epilepsy. Because of the consistent presence of pyramidal tract affection in GPT2 patients, we further suggest that GPT2 mutations should be considered in cases with complex hereditary spastic paraplegia.
Sexual behavior and testis morphology in the BACHD rat model
2018-06-08

The testis phenotype in the BACHD rat model does not mimic the changes observed in human HD testis. The altered sexual behavior in BACHD rats at three months of age could be to a certain extent representative of and share common underlying pathways with some of the sexual disturbances in HD patients. Further investigating the biological causes of the sexual phenotype in BACHD rats may therefore contribute to clarifying the mechanisms at the base of sexual behavior changes in HD.
Spin State in Perfluorinated FePc Films on Cu(111) and Ag(111) in Dependence on Film Thickness
2018-06-08

&lt;p&gt;The electronic structure of the central iron ion of perfluorinated iron phthalocyanine (FePcF&lt;sub&gt;16&lt;/sub&gt;) in thin films has been studied on Cu(111) and Ag(111) using polarization dependent X-ray absorption spectroscopy (XAS). The data are compared to FePc on Ag(111). Ligand field parameters have been computed, and multiplet calculations (CTM4XAS) were carried out to simulate XAS spectra. The planar molecules are preferentially oriented lying flat on the substrate surface during the growth of the 1-4 nm thick films. A clear polarization dependence of the Fe L edge absorption spectra is observed, arising from transitions into orbitals with in-plane and out-of-plane character. The shape of the spectra for three to four monolayers of FePcF&lt;sub&gt;16&lt;/sub&gt; on Cu(111) is comparable to that of the thin films of FePc on Ag(111). However, a drastic change of the XAS peak shape is observed for thicker FePcF&lt;sub&gt;16&lt;/sub&gt; films on both Ag(111) and Cu(111), although the molecular orientation is very similar to coverages consisting of a few monolayers. Since in both cases the film thickness is distinctly beyond the monolayer regime, interface interactions can be ruled out as a possible origin of this behavior. Rather, the different XAS peak shapes seem to indicate that the multiplicity may depend on the detailed arrangement of the FePcF&lt;sub&gt;16&lt;/sub&gt; molecules. The large flexibility of the ground state of Fe could be of high interest for spintronic applications.&lt;/p&gt;
Histiocytic necrotising lymphadenitis identical to Kikuchi-Fujimoto disease in CNS lupus
2018-06-08

A 36-year-old woman presented after a first generalised tonic–clonic seizure. On clinical examination, prominent cervical and axillary lymphadenopathy was noted. Brain MRI showed diffuse, partially enhancing, hyperintense lesions (figure 1). An axillary lymph node biopsy revealed typical findings of histiocytic necrotising lymphadenitis, compatible with Kikuchi-Fujimoto disease (figure 2).1 Laboratory studies showed positive antinuclear antibodies, low complement levels and pancytopenia. In the cerebrospinal fluid (CSF), lymphocytic pleocytosis (34/μL), elevated lactate (3.3 mmol/L) and protein (104 mg/dL) levels were noted. Investigations for lymphoma were negative. Furthermore, negative serological and PCR findings for Epstein-Barr virus, cytomegalovirus and HIV were found. Interferon-gamma release assay and PCR for tuberculosis, along with serological investigations for toxoplasmosis and syphilis, were negative. The cytological ...
A case study for late Archean and Proterozoic biogeochemical iron‐ and sulphur cycling in a modern habitat—the Arvadi Spring
2018-06-09

Abstract As a consequence of Earth's surface oxygenation, ocean geochemistry changed from ferruginous (iron( II )‐rich) into more complex ferro‐euxinic (iron( II )‐sulphide‐rich) conditions during the Paleoproterozoic. This transition must have had profound implications for the Proterozoic microbial community that existed within the ocean water and bottom sediment; in particular, iron‐oxidizing bacteria likely had to compete with emerging sulphur‐metabolizers. However, the nature of their coexistence and interaction remains speculative. Here, we present geochemical and microbiological data from the Arvadi Spring in the eastern Swiss Alps, a modern model habitat for ferro‐euxinic transition zones in late Archean and Proterozoic oceans during high‐oxygen intervals, which enables us to reconstruct the microbial community structure in respective settings for this geological era. The spring water is oxygen‐saturated but still contains relatively elevated concentrations of dissolved iron( II ) (17.2 ± 2.8 μM) and sulphide (2.5 ± 0.2 μM) with simultaneously high concentrations of sulphate (8.3 ± 0.04 mM). Solids consisting of quartz, calcite, dolomite and iron( III ) oxyhydroxide minerals as well as sulphur‐containing particles, presumably elemental S 0 , cover the spring sediment. Cultivation‐based most probable number counts revealed microaerophilic iron( II )‐oxidizers and sulphide‐oxidizers to represent the largest fraction of iron‐ and sulphur‐metabolizers in the spring, coexisting with less abundant iron( III )‐reducers, sulphate‐reducers and phototrophic and nitrate‐reducing iron( II )‐oxidizers. 16S rRNA gene 454 pyrosequencing showed sulphide‐oxidizing Thiothrix species to be the dominating genus, supporting the results from our cultivation‐based assessment. Collectively, our results suggest that anaerobic and microaerophilic iron‐ and sulphur‐metabolizers could have coexisted in oxygenated ferro‐sulphidic transition zones of late Archean and Proterozoic oceans, where they would have sustained continuous cycling of iron and sulphur compounds.
SGK1 induces vascular smooth muscle cell calcification through NF-κB signaling
2018-06-10

Medial vascular calcification, associated with enhanced mortality in chronic kidney disease (CKD), is fostered by osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Here, we describe that serum- and glucocorticoid-inducible kinase 1 (SGK1) was upregulated in VSMCs under calcifying conditions. In primary human aortic VSMCs, overexpression of constitutively active SGK1S422D, but not inactive SGK1K127N, upregulated osteo-/chondrogenic marker expression and activity, effects pointing to increased osteo-/chondrogenic transdifferentiation. SGK1S422D induced nuclear translocation and increased transcriptional activity of NF-κB. Silencing or pharmacological inhibition of IKK abrogated the osteoinductive effects of SGK1S422D. Genetic deficiency, silencing, and pharmacological inhibition of SGK1 dissipated phosphate-induced calcification and osteo-/chondrogenic transdifferentiation of VSMCs. Aortic calcification, stiffness, and osteo-/chondrogenic transdifferentiation in mice following cholecalciferol overload were strongly reduced by genetic knockout or pharmacological inhibition of Sgk1 by EMD638683. Similarly, Sgk1 deficiency blunted vascular calcification in apolipoprotein E-deficient mice after subtotal nephrectomy. Treatment of human aortic smooth muscle cells with serum from uremic patients induced osteo-/chondrogenic transdifferentiation, effects ameliorated by EMD638683. These observations identified SGK1 as a key regulator of vascular calcification. SGK1 promoted vascular calcification, at least partly, via NF-κB activation. Inhibition of SGK1 may, thus, reduce the burden of vascular calcification in CKD.
Acceleration of Magnetic Resonance Cholangiopancreatography Using Compressed Sensing at 1.5 and 3 T
2018-06-10

Objectives Magnetic resonance cholangiopancreatography (MRCP) is an established technique in routine magnetic resonance examination. By applying the compressed sensing (CS) acceleration technique to conventional MRCP sequences, scan time can be markedly reduced. With promising results at 3 T, there is a necessity to evaluate the performance at 1.5 T due to wide scanner availabilities. Aim of this study is to test the feasibility of accelerated 3-dimensional (3D) MRCP with extended sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) using CS in navigator triggering and in a single breath-hold in a clinical setting at 1.5 T and 3 T and compare it with a conventional navigator-triggered 3D SPACE-MRCP. Materials and Methods Phantom measurements were performed to adapt sequence parameters. Conventional 3D SPACE-MRCP in navigator triggering (STD_MRCP) as well as CS-accelerated 3D SPACE-MRCP acquired in navigator triggering and in a single breath-hold (CS_MRCP and CS_BH_MRCP) was performed in 66 patients undergoing clinically induced MRI of the pancreatobiliary system at 1.5 T and 3 T. Image quality evaluation was performed by 2 independent radiologists. Dedicated statistics were performed ( P &lt; 0.05 considered significant). Results In patient imaging, CS_MRCP was superior to STD_MRCP and CS_BH_MRCP in aspects of overall image quality at 1.5 T ( P = 0.01; P &lt; 0.001) and 3 T ( P = 0.002; P = 0.013). Overall image quality in CS_BH_MRCP was inferior compared with STD_MRCP and CS_MRCP at 1.5 T. At 3 T, overall image quality in CS_BH_MRCP was superior to STD_MRCP ( P = 0.001). Scan time was reduced by 25% to 46% covering 5% of k-space (CS_MRCP at 1.5 and 3 T) and 97% covering 3.6% of k-space (CS_BH_MRCP at 1.5 and 3 T). Conclusions Compressed sensing-accelerated MRCP is feasible in clinical routine at 1.5 and 3 T offering major reduction of acquisition time. When applying a single breath-hold CS imaging, field strengths of 3 T are recommended.
Leaked GeV CRs from a Broken Shell: Explaining 9 Years of Fermi-LAT Data of SNR W28
2018-06-10

Abstract Supernova remnant (SNR)W28 is well known for its classic hadronic scenario, in which the TeV cosmic rays (CRs) released at the early stage of this intermediate-age SNR illuminate nearby molecular clouds (MCs). Overwhelming evidence has shown that the northeastern part of the SNR (W28-North) has already encountered the MC clumps. Through this broken shell W28-North, CRs with an energy down to &lt;1 GeV may be able to be injected into nearby MCs. To further verify this hadronic scenario, we first analyze nine years of Fermi- LAT data in/around W28 with energies down to 0.3 GeV. Our Fermi- LAT analysis displays a 10–200 GeV skymap that spatially matches the known TeV sources HESS J1801–233 (W28-North) and HESS J1800–240 A, B, and C (240 A B and C) well. At low energy bands, we have discovered a 0.5–1 GeV blob located to the south of 240 B and C, and a low flux of 0.3–1 GeV at 240 A. A hadronic model is build to explain our analysis results and previous multiwavelength observations of W28. Our model consists of three CR sources: the run-away CRs escaped from a strong shock, the leaked GeV CRs from the broken shell W28-North, and the local CR sea. Through modeling the SNR evolution and the CR acceleration and release, we explain the GeV–TeV emission in/around SNR W28 (except for 240 A) in one model. The damping of the magnetic waves by the neutrals and the decreased acceleration efficiency are both taken into account in our model due to the intermediate age of SNR W28.
Plant-Derived Drugs in Malaria Treatment
2018-06-10

Every year 880,000 people are killed by malaria, mostof them children in impoverished regions of the worldlacking adequate medical care. While many preventativemeasures, such as mosquito nets have decreased theincidence of malaria, once the disease is contracted,it must be treated. Many plasmodial species havedeveloped a frightening resistance to antimalarial agents,making the search for new, effective antimalarial agentsan urgent priority of global importance.
Abrupt or gradual? Change point analysis of the late Pleistocene–Holocene climate record from Chew Bahir, southern Ethiopia
2018-06-11

Abstract We used a change point analysis on a late Pleistocene–Holocene lake-sediment record from the Chew Bahir basin in the southern Ethiopian Rift to determine the amplitude and duration of past climate transitions. The most dramatic changes occurred over 240 yr (from ~15,700 to 15,460 yr) during the onset of the African Humid Period (AHP), and over 990 yr (from ~4875 to 3885 yr) during its protracted termination. The AHP was interrupted by a distinct dry period coinciding with the high-latitude Younger Dryas stadial, which had an abrupt onset (less than ~100 yr) at ~13,260 yr and lasted until ~11,730 yr. Wet-dry-wet transitions prior to the AHP may reflect the high-latitude Dansgaard-Oeschger cycles, as indicated by cross-correlation of the potassium record with the NorthGRIP ice core record between ~45–20 ka. These findings may contribute to the debates regarding the amplitude, and duration and mechanisms of past climate transitions, and their possible influence on the development of early modern human cultures.
Collagen stable isotopes provide insights into the end of the mammoth steppe in the central East European plains during the Epigravettian
2018-06-11

Abstract Higher δ 15 N values in bone collagen of mammoth ( Mammuthus primigenius ) compared with coeval large herbivores is a classic trait of the mammoth steppe. An exception applies to the Epigravettian site of Mezhyrich (ca. 18–17.4 ka cal BP) in the central East European plains, where mammoth bones have δ 15 N values equivalent to or in a lower range than those of horse specimens ( Equus sp.). We expanded our preliminary dataset to a larger sampling size of mammoth, other large herbivores, and carnivores from contemporaneous and nearby sites of Buzhanka 2, Eliseevichi, and Yudinovo. The unusual low mammoth δ 15 N values were confirmed at Buzhanka 2 and for some specimens from Eliseevichi, while most individuals from Yudinovo displayed the expected high δ 15 N values, meaning similar to those of the large canids. The possibility of a contrast in migration pattern is not supported since the δ 34 S values, a marker of mobility, do not correlate with the δ 15 N values of mammoth bone collagen. No clear chronological tendency could be revealed, at least not at the scale of radiocarbon dating. The low range in δ 15 N values is likely to reflect a change in the specific niche of the mammoth in the southern part of its distribution.
Even subtle cultural differences affect face tuning
2018-06-11

Culture shapes social cognition in many ways. Yet cultural impact on face tuning remains largely unclear. Here typically developing females and males from the French-speaking part of Switzerland were presented with a set of Arcimboldo-like Face-n-Food images composed of food ingredients and in different degree resembling a face. The outcome had been compared with previous findings obtained in young adults of the South-West Germany. In that study, males exhibit higher thresholds for face tuning on the Face-n-Food task than females. In Swiss participants, no gender differences exist in face tuning. Strikingly, males from the French-speaking part of Switzerland possess higher sensitivity to faces than their German peers, whereas no difference in face tuning occurs between females. The outcome indicates that even relatively subtle cultural differences as well as culture by gender interaction can modulate social cognition. Clarification of the nature of cultural impact on face tuning as well as social cognition at large is of substantial value for understanding a wide range of neuropsychiatric and neurodevelopmental conditions.
Generation of an induced pluripotent stem cell line from a patient with spinocerebellar ataxia type 3 (SCA3): HIHCNi002-A
2018-06-11

A skin biopsy of a patient with spinocerebellar ataxia type 3 (SCA3, also known as Machado-Joseph disease (MJD)) caused by a CAG trinucleotide repeat expansion in the ATXN3 gene, was used to generate an induced pluripotent stem cell line, HIHCNi002-A (iPSC-SCA3). Skin fibroblasts were reprogrammed using episomal plasmids carrying hOCT4, hSOX2, hKLF4, hL-MYC, and hLIN28. The iPSC-SCA3 line exhibits chromosomal stability with conservation of the ATXN3 repeat expansion, expresses pluripotency markers and differentiates into endo-, meso-, and ectodermal cells in vitro.
Short-term exposure enhances perception of both between- and within-category acoustic information
2018-06-11

A critical question in speech research is how listeners use non-discrete acoustic cues for discrimination between discrete alternative messages (e.g. words). Previous studies have shown that distributional learning can improve listeners’ discrimination of non-native speech sounds. Less is known about effects of training on perception of within-category acoustic detail. The present research investigates adult listeners’ perception of and discrimination between lexical tones without training or after a brief training exposure. Native speakers of German (a language without lexical tone) heard a 13-step pitch continuum of the syllable /li:/. Two different tasks were used to assess sensitivity to acoustic differences on this continuum: a) pitch height estimation and b) AX discrimination. Participants performed these tasks either without exposure or after exposure to a bimodal distribution of the pitch continuum. The AX discrimination results show that exposure to a bimodal distribution enhanced discrimination at the category boundary (i.e. categorical perception) of high vs. low tones. Interestingly, the pitch estimation task results followed a categorisation (sigmoid) function without exposure, but a linear function after exposure, suggesting estimates became less categorical in this task. The results suggest that training exposure may enhance not only discrimination between contrastive speech sounds (consistent with previous studies), but also perception of within-category acoustic differences. Different tasks may reveal different skills.