julilili42/papers huggingface dataset:
Neutral sphingomyelinases control extracellular vesicles budding from the plasma membrane
2017-09-27

ABSTRACT Extracellular vesicles (EVs) are membrane particles secreted from cells into all body fluids. Several EV populations exist differing in size and cellular origin. Using differential centrifugation EVs pelleting at 14,000 g (“microvesicles” (MV)) and 100,000 g (“exosomes”) are distinguishable by protein markers. Neutral sphingomyelinase (nSMase) inhibition has been shown to inhibit exosome release from cells and has since been used to study their functional implications. How nSMases (also known as SMPD2 and SMPD3) affect the basal secretion of MVs is unclear. Here we investigated how SMPD2/3 impact both EV populations. SMPD2/3 inhibition by GW4869 or RNAi decreases secretion of exosomes, but also increases secretion of MVs from the plasma membrane. Both populations differ significantly in metabolite composition and Wnt proteins are specifically loaded onto MVs under these conditions. Taken together, our data reveal a novel regulatory function of SMPD2/3 in vesicle budding from the plasma membrane and clearly suggest that – despite the different vesicle biogenesis – the routes of vesicular export are adaptable.
Haploidentical transplant in patients with myelodysplastic syndrome
2017-09-27

Key Points Nonrelapse mortality remains high in MDS patients who underwent haploidentical transplant before 2015. Haplotransplantation using PT-CY and reduced-intensity conditioning seems an acceptable option in MDS patients lacking HLA-matched donors.
Shared genetic risk between migraine and coronary artery disease: A genome-wide analysis of common variants
2017-09-28

Migraine is a recurrent pain condition traditionally viewed as a neurovascular disorder, but little is known of its vascular basis. In epidemiological studies migraine is associated with an increased risk of cardiovascular disease, including coronary artery disease (CAD), suggesting shared pathogenic mechanisms. This study aimed to determine the genetic overlap between migraine and CAD, and to identify shared genetic risk loci, utilizing a conditional false discovery rate approach and data from two large-scale genome-wide association studies (GWAS) of CAD (C4D, 15,420 cases, 15,062 controls; CARDIoGRAM, 22,233 cases, 64,762 controls) and one of migraine (22,120 cases, 91,284 controls). We found significant enrichment of genetic variants associated with CAD as a function of their association with migraine, which was replicated across two independent CAD GWAS studies. One shared risk locus in the PHACTR1 gene (conjunctional false discovery rate for index SNP rs9349379 < 3.90 x 10-5), which was also identified in previous studies, explained much of the enrichment. Two further loci (in KCNK5 and AS3MT) showed evidence for shared risk (conjunctional false discovery rate < 0.05). The index SNPs at two of the three loci had opposite effect directions in migraine and CAD. Our results confirm previous reports that migraine and CAD share genetic risk loci in excess of what would be expected by chance, and highlight one shared risk locus in PHACTR1. Understanding the biological mechanisms underpinning this shared risk is likely to improve our understanding of both disorders.
A Multidimensional Approach to International Market Selection and Nation Branding in Sub-saharan Africa
2017-09-28

Despite the strong economic growth of many African countries, foreign investors often overlook their potential. Nation branding can raise the awareness of foreign investors to the particular strengths of these countries. To identify the specific image attributes of a nation that nation branding campaigns could prioritize, 144 managers evaluated the importance of 22 market selection criteria. In this study, using the analytical hierarchy process, we weighed those dimensions, condensing multifaceted information into a framework to evaluate the attractiveness of African countries for foreign direct investment (FDI). We subsequently applied this framework to 46 sub-Saharan nations. The results highlight the diversity among these countries, provide guidance for nation branding and serve to alert investors to frequently overlooked target markets. Our study substantially contributes to international market selection research by introducing a new screening method for emerging markets.
Gradual progression from sensory to task-related processing in cerebral cortex
2017-09-28

Abstract Somewhere along the cortical hierarchy, behaviorally relevant information is distilled from raw sensory inputs. We examined how this transformation progresses along multiple levels of the hierarchy by comparing neural representations in visual, temporal, parietal, and frontal cortices in monkeys categorizing across three visual domains (shape, motion direction, color). Representations in visual areas MT and V4 were tightly linked to external sensory inputs. In contrast, lateral prefrontal cortex (PFC) largely represented the abstracted behavioral relevance of stimuli (task rule, motion category, color category). Intermediate-level areas—posterior inferotemporal (PIT), lateral intraparietal (LIP), and frontal eye fields (FEF)—exhibited mixed representations. While the distribution of sensory information across areas aligned well with classical functional divisions—MT carried stronger motion information, V4 and PIT carried stronger color and shape information—categorical abstraction did not, suggesting these areas may participate in different networks for stimulus-driven and cognitive functions. Paralleling these representational differences, the dimensionality of neural population activity decreased progressively from sensory to intermediate to frontal cortex. This shows how raw sensory representations are transformed into behaviorally relevant abstractions and suggests that the dimensionality of neural activity in higher cortical regions may be specific to their current task. Significance statement The earliest stages of processing in cerebral cortex reflect a relatively faithful copy of sensory inputs, but intelligent behavior requires abstracting behaviorally relevant concepts and categories. We examined how this transformation progresses through multiple levels of the cortical hierarchy by comparing neural representations in six cortical areas in monkeys categorizing across three visual domains. We found that categorical abstraction occurred in a gradual fashion across the cortical hierarchy and reached an apex in prefrontal cortex. Categorical coding did not respect classical models of large-scale cortical organization. The dimensionality of neural population activity was reduced in parallel with these representational changes. Our results shed light on how raw sensory inputs are transformed into behaviorally relevant abstractions.
In-medium bound states and pairing gap
2017-09-28

The propagator of two nucleons in infinite nuclear matter is evaluated by a diagonalization of the RPA Hamiltonian. This effective Hamiltonian is non-Hermitian and, for specific density domains and partial waves, yields pairs of complex conjugated eigenvalues representing in-medium bound states of two nucleons. The occurrence of these complex poles in the two-particle Greens function is tightly related to the well known BCS pairing approach. It is demonstrated that these complex eigenvalues and the corresponding bound state wavefunctions contain all information about the BCS gap function. This is illustrated by calculations for and pairing gaps in neutron matter which essentially coincide with the corresponding gap functions extracted from conventional solutions of the gap equation. Differences between the bound states in the conventional BCS approach and the RPA are arising in the case of channel in symmetric nuclear matter at low densities. These differences are discussed in the context of transition from BEC for quasi-deuterons to the formation of BCS pairing.
Supersonic gas streams enhance the formation of massive black holes in the early universe
2017-09-29

Making the first supermassive black holes Supermassive black holes existed less than a billion years after the Big Bang. Because black holes can grow at a maximum rate that depends on their current mass, it has been difficult to understand how such massive black holes could have formed so quickly. Hirano et al. developed simulations to show that streaming motions—velocity offsets between the gas and dark matter components—could have produced black holes with tens of thousands of solar masses in the early universe. That's big enough to grow into the supermassive black holes that we observe today. Science , this issue p. 1375
Forming spectroscopic massive protobinaries by disc fragmentation
2017-09-29

The surroundings of massive protostars constitute an accretion disc which has numerically been shown to be subject to fragmentation and responsible for luminous accretion-driven outbursts. Moreover, it is suspected to produce close binary companions which will later strongly influence the star's future evolution in the Hertzsprung-Russel diagram. We present three-dimensional gravitation-radiation-hydrodynamic numerical simulations of 100 Mo pre-stellar cores. We find that accretion discs of young massive stars violently fragment without preventing the (highly variable) accretion of gaseous clumps onto the protostars. While acquiring the characteristics of a nascent low-mass companion, some disc fragments migrate onto the central massive protostar with dynamical properties showing that its final Keplerian orbit is close enough to constitute a close massive proto-binary system, having a young high-mass and a low-mass component. We conclude on the viability of the disc fragmentation channel for the formation of such short-period binaries, and that both processes -close massive binary formation and accretion bursts- may happen at the same time. FU-Orionis-type bursts, such as observed in the young high-mass star S255IR-NIRS3, may not only indicate ongoing disc fragmentation, but also be considered as a tracer for the formation of close massive binaries - progenitors of the subsequent massive spectroscopic binaries - once the high-mass component of the system will enter the main-sequence phase of its evolution. Finally, we investigate the ALMA-observability of the disc fragments.
Post-Kerr black hole spectroscopy
2017-09-29

One of the central goals of the newborn field of gravitational wave astronomy is to test gravity in the highly nonlinear, strong field regime characterizing the spacetime of black holes. In particular, "black hole spectroscopy" (the observation and identification of black hole quasinormal mode frequencies in the gravitational wave signal) is expected to become one of the main tools for probing the structure and dynamics of Kerr black holes. In this paper we take a significant step towards that goal by constructing a "post-Kerr" quasinormal mode formalism. The formalism incorporates a parametrized but general perturbative deviation from the Kerr metric and exploits the well-established connection between the properties of the spacetime's circular null geodesics and the fundamental quasinormal mode to provide approximate, eikonal limit formulae for the modes' complex frequencies. The resulting algebraic toolkit can be used in waveform templates for ringing black holes with the purpose of measuring deviations from the Kerr metric. As a first illustrative application of our framework, we consider the Johannsen-Psaltis deformed Kerr metric and compute the resulting deviation in the quasinormal mode frequency relative to the known Kerr result.
Perovskite solar cells with CuSCN hole extraction layers yield stabilized efficiencies greater than 20%
2017-09-30

Transporter layers improve stability Although perovskite solar cells can have power conversion efficiencies exceeding 20%, they can have limited thermal and ultraviolet irradiation stability. This is in part because of the materials used to extract the charge carriers (electrons and holes) from the active layer. Arora et al. replaced organic hole transporter layers with CuCSN to improve thermal stability. Device lifetime was enhanced when a conducting reduced graphene oxide spacer was added between the CuSCN layer and the gold electrode. Science , this issue p. 768
Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial
2017-09-30

Spastic paraplegia type 5 (SPG5) is a rare subtype of hereditary spastic paraplegia, a highly heterogeneous group of neurodegenerative disorders defined by progressive neurodegeneration of the corticospinal tract motor neurons. SPG5 is caused by recessive mutations in the gene CYP7B1 encoding oxysterol-7α-hydroxylase. This enzyme is involved in the degradation of cholesterol into primary bile acids. CYP7B1 deficiency has been shown to lead to accumulation of neurotoxic oxysterols. In this multicentre study, we have performed detailed clinical and biochemical analysis in 34 genetically confirmed SPG5 cases from 28 families, studied dose-dependent neurotoxicity of oxysterols in human cortical neurons and performed a randomized placebo-controlled double blind interventional trial targeting oxysterol accumulation in serum of SPG5 patients. Clinically, SPG5 manifested in childhood or adolescence (median 13 years). Gait ataxia was a common feature. SPG5 patients lost the ability to walk independently after a median disease duration of 23 years and became wheelchair dependent after a median 33 years. The overall cross-sectional progression rate of 0.56 points on the Spastic Paraplegia Rating Scale per year was slightly lower than the longitudinal progression rate of 0.80 points per year. Biochemically, marked accumulation of CYP7B1 substrates including 27-hydroxycholesterol was confirmed in serum (n = 19) and cerebrospinal fluid (n = 17) of SPG5 patients. Moreover, 27-hydroxycholesterol levels in serum correlated with disease severity and disease duration. Oxysterols were found to impair metabolic activity and viability of human cortical neurons at concentrations found in SPG5 patients, indicating that elevated levels of oxysterols might be key pathogenic factors in SPG5. We thus performed a randomized placebo-controlled trial (EudraCT 2015-000978-35) with atorvastatin 40 mg/day for 9 weeks in 14 SPG5 patients with 27-hydroxycholesterol levels in serum as the primary outcome measure. Atorvastatin, but not placebo, reduced serum 27-hydroxycholesterol from 853 ng/ml [interquartile range (IQR) 683-1113] to 641 (IQR 507-694) (-31.5%, P = 0.001, Mann-Whitney U-test). Similarly, 25-hydroxycholesterol levels in serum were reduced. In cerebrospinal fluid 27-hydroxycholesterol was reduced by 8.4% but this did not significantly differ from placebo. As expected, no effects were seen on clinical outcome parameters in this short-term trial. In this study, we define the mutational and phenotypic spectrum of SPG5, examine the correlation of disease severity and progression with oxysterol concentrations, and demonstrate in a randomized controlled trial that atorvastatin treatment can effectively lower 27-hydroxycholesterol levels in serum of SPG5 patients. We thus demonstrate the first causal treatment strategy in hereditary spastic paraplegia.
Granulocytic myeloid-derived suppressor cells (GR-MDSC) accumulate in cord blood of preterm infants and remain elevated during the neonatal period
2017-09-30

Summary Preterm delivery is the leading cause of perinatal morbidity and mortality. Among the most important complications in preterm infants are peri- or postnatal infections. Myeloid-derived suppressor cells (MDSC) are myeloid cells with suppressive activity on other immune cells. Emerging evidence suggests that granulocytic MDSC (GR-MDSC) play a pivotal role in mediating maternal–fetal tolerance. The role of MDSC for postnatal immune-regulation in neonates is incompletely understood. Until the present time, nothing was known about expression of MDSC in preterm infants. In the present pilot study, we quantified GR-MDSC counts in cord blood and peripheral blood of preterm infants born between 23 + 0 and 36 + 6 weeks of gestation (WOG) during the first 3 months of life and analysed the effect of perinatal infections. We show that GR-MDSC are increased in cord blood independent of gestational age and remain elevated in peripheral blood of preterm infants during the neonatal period. After day 28 they drop to nearly adult levels. In case of perinatal or postnatal infection, GR-MDSC accumulate further and correlate with inflammatory markers C-reactive protein (CRP) and white blood cell counts (WBC). Our results point towards a role of GR-MDSC for immune-regulation in preterm infants and render them as a potential target for cell-based therapy of infections in these patients.
TRPM8 is required for survival and radioresistance of glioblastoma cells
2017-09-30

TRPM8 is a Ca -permeable nonselective cation channel belonging to the melastatin sub-group of the transient receptor potential (TRP) family. TRPM8 is aberrantly overexpressed in a variety of tumor entities including glioblastoma multiforme where it reportedly contributes to tumor invasion. The present study aimed to disclose further functions of TRPM8 in glioma biology in particular upon cell injury by ionizing radiation. To this end, TCGA data base was queried to expose the TRPM8 mRNA abundance in human glioblastoma specimens and immunoblotting was performed to analyze the TRPM8 protein abundance in primary cultures of human glioblastoma. Moreover, human glioblastoma cell lines were irradiated with 6 MV photons and TRPM8 channels were targeted pharmacologically or by RNA interference. TRPM8 abundance, Ca signaling and resulting K channel activity, chemotaxis, cell migration, clonogenic survival, DNA repair, apoptotic cell death, and cell cycle control were determined by qRT-PCR, fura-2 Ca imaging, patch-clamp recording, transfilter migration assay, wound healing assay, colony formation assay, immunohistology, flow cytometry, and immunoblotting. As a result, human glioblastoma upregulates TRPM8 channels to variable extent. TRPM8 inhibition or knockdown slowed down cell migration and chemotaxis, attenuated DNA repair and clonogenic survival, triggered apoptotic cell death, impaired cell cycle and radiosensitized glioblastoma cells. Mechanistically, ionizing radiation activated and upregulated TRPM8-mediated Ca signaling that interfered with cell cycle control probably via CaMKII, cdc25C and cdc2. Combined, our data suggest that TRPM8 channels contribute to spreading, survival and radioresistance of human glioblastoma and, therefore, might represent a promising target in future anti-glioblastoma therapy.
INFLUENCE OF AGE ON PARAMETERS FOR FEMOROACETABULAR IMPINGEMENT AND HIP DYSPLASIA IN X-RAYS
2017-09-30

ABSTRACT Objective: While several radiographic parameters have been established to describe the geometry and pathology of the hip, their reference values and clinical significance remain a matter of dispute. The present study tests the hypothesis that age has a relevant impact on radiographic hip parameters. Method: Pelvic antero-posterior views were measured for CE angle, Sharp’s angle, acetabular depth-to-width ratio, femoral head extrusion index, roof obliquity, caput-collum-diaphyseal (CCD) angle, and Murray’s femoral head ratio, and the values obtained were correlated with age. Results: Significant weak and moderate linear correlations (all Ps&lt;0.001) were observed between age and CE angle (ρ=0.31), Sharp’s angle (ρ=-0.38), extrusion index (ρ=-0.22), CCD angle (ρ=-0.15), depth-to-width ratio (ρ=-0.38), and roof obliquity (ρ=-0.19), while Murray’s femoral head ratio (ρ=0.05; P=0.274) was not associated with age. Interestingly, the parameters describing the acetabulum all showed a relevant increase in coverage with age, leading to CE-angles well beyond 40° and a Sharp’s angle below 35° in a large portion of asymptomatic older adults. Conclusion: While a decrease in CCD angle with age is described in most orthopedic textbooks, the changes observed with age in acetabular geometry far exceed those measured at the femoral head-neck junction. We recommend considering these alterations that may be attributable to age when formulating a radiographic diagnosis. Level of Evidence III, Diagnostic Studies - Investigating a Diagnostic Test.
Between Critique and Reception of Philosophical Traditions
2017-09-30

Ṣāʾin al-Dīn ibn Turka al-Iṣfahānī (d. 1432) is among the most neglected figures in the history of Arabic-Islamic philosophy. True, his Tamhīd al-qawāʿid (“Introduction to the Principles,” TQ) has been highly evaluated within the Iranian ʿirfān circle since the late Qajar period; as the author of TQ, he is considered in this circle to be a precursor of Mullā Ṣadrā’s (d. 1640) alleged “synthesis” of Ibn al-ʿArabī’s (d. 1240) Akbarian mysticism, al-Suhrawardī’s (d. 1191) illuminationist philosophy, and al-Ṭūsī’s (d. 1274) revived Avicennian philosophy. Modern historians, however, adopt this evaluation while conducting, effectively, no detailed analysis of the contents of the work. Even Melvin-Koushki, who explores in detail the lettrist-occultist dimensions of this politically afflicted polymath’s Weltanschauung, has not gone so far as to redress their inaccurate understanding of TQ itself.
Understanding Low- and High-Level Contributions to Fixation Prediction
2017-10-01

Understanding where people look in images is an important problem in computer vision. Despite significant research, it remains unclear to what extent human fixations can be predicted by low-level (contrast) compared to highlevel (presence of objects) image features. Here we address this problem by introducing two novel models that use different feature spaces but the same readout architecture. The first model predicts human fixations based on deep neural network features trained on object recognition. This model sets a new state-of-the art in fixation prediction by achieving top performance in area under the curve metrics on the MIT300 hold-out benchmark (AUC = 88%, sAUC = 77%, NSS = 2.34). The second model uses purely low-level (isotropic contrast) features. This model achieves better performance than all models not using features pretrained on object recognition, making it a strong baseline to assess the utility of high-level features. We then evaluate and visualize which fixations are better explained by lowlevel compared to high-level image features. Surprisingly we find that a substantial proportion of fixations are better explained by the simple low-level model than the stateof- the-art model. Comparing different features within the same powerful readout architecture allows us to better understand the relevance of low- versus high-level features in predicting fixation locations, while simultaneously achieving state-of-the-art saliency prediction.