bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-nucleotide polymorphisms in Orai1 associated with atopic dermatitis inhibit protein turnover, decrease calcium entry and disrupt calcium-dependent gene expression
Authors: Yeh Yi-Chun , Lin Yu-Ping , Kramer Holger , Parekh Anant B 
Published: September 2019

AbstractLoss-of function mutations in Orai1 Ca2+ channels lead to a form of severe combined immunodeficiency, auto-immunity, muscle hypotonia and defects in dental enamel production and sweat gland function. Two single-nucleotide polymorphisms (SNPs) in Orai1 have been found and localize to the second extracellular loop. These polymorphisms associate with atopic dermatitis but how they affect Ca2+ signalling and cell function is unknown. Here, we find that Orai1–SNPs turnover considerably more slowly than wild type Orai1 and are more abundantly expressed in the plasma membrane. We show a central role for flotillin in the endocytotic recycling of Orai1 channels and that endocytosed wild type Orai1 is trafficked to Rab 7-positive late endosomes for lysosomal degradation. Orai1–SNPs escape the degradation pathway and instead enter Rab 11-positive recycling endosomes, where they are returned to the surface membrane through Arf6-dependent exocytosis. We find that Orai1–SNPs escape late endosomes through endosomal pH regulation of interaction between the channel and flotillin. We identify a pH-sensitive electrostatic interaction between positively charged arginine in extracellular loop 2 (K210) and a negatively charged aspartate (D112) in extracellular loop 1 that helps determine Orai1 turnover. The increase in membrane Orai1–SNP leads to a mis-match in Orai1–STIM stoichiometry, resulting in inhibition of Ca2+ entry and Ca2+-dependent gene expression. Our results identify new strategies for targeting atopic dermatitis.
Concentration inequalities for the empirical distribution of discrete distributions: beyond the method of types
Authors: Mardia Jay , Jiao Jiantao , Tánczos Ervin , Nowak Robert D , Weissman Tsachy 
Published: September 2019

Abstract
We study concentration inequalities for the Kullback–Leibler (KL) divergence between the empirical distribution and the true distribution. Applying a recursion technique, we improve over the method of types bound uniformly in all regimes of sample size $n$ and alphabet size $k$, and the improvement becomes more significant when $k$ is large. We discuss the applications of our results in obtaining tighter concentration inequalities for $L_1$ deviations of the empirical distribution from the true distribution, and the difference between concentration around the expectation or zero. We also obtain asymptotically tight bounds on the variance of the KL divergence between the empirical and true distribution, and demonstrate their quantitatively different behaviours between small and large sample sizes compared to the alphabet size.
Using natural language processing to construct a metastatic breast cancer cohort from linked cancer registry and electronic medical records data
Authors: Ling Albee Y , Kurian Allison W , Caswell-Jin Jennifer L , Sledge George W , Shah Nigam H , Tamang Suzanne R 
Published: September 2019

AbstractObjectivesMost population-based cancer databases lack information on metastatic recurrence. Electronic medical records (EMR) and cancer registries contain complementary information on cancer diagnosis, treatment and outcome, yet are rarely used synergistically. To construct a cohort of metastatic breast cancer (MBC) patients, we applied natural language processing techniques within a semisupervised machine learning framework to linked EMR-California Cancer Registry (CCR) data.Materials and MethodsWe studied all female patients treated at Stanford Health Care with an incident breast cancer diagnosis from 2000 to 2014. Our database consisted of structured fields and unstructured free-text clinical notes from EMR, linked to CCR, a component of the Surveillance, Epidemiology and End Results Program (SEER). We identified de novo MBC patients from CCR and extracted information on distant recurrences from patient notes in EMR. Furthermore, we trained a regularized logistic regression model for recurrent MBC classification and evaluated its performance on a gold standard set of 146 patients.ResultsThere were 11 459 breast cancer patients in total and the median follow-up time was 96.3 months. We identified 1886 MBC patients, 512 (27.1%) of whom were de novo MBC patients and 1374 (72.9%) were recurrent MBC patients. Our final MBC classifier achieved an area under the receiver operating characteristic curve (AUC) of 0.917, with sensitivity 0.861, specificity 0.878, and accuracy 0.870.Discussion and ConclusionTo enable population-based research on MBC, we developed a framework for retrospective case detection combining EMR and CCR data. Our classifier achieved good AUC, sensitivity, and specificity without expert-labeled examples.
Farmers’ Knowledge and Practices in the Management of Insect Pests of Leafy Amaranth in Kenya
Authors: Nampeera Esther L , Nonnecke Gail R , Blodgett Sue L , Tusiime Sharon M , Masinde Dorothy M , Wesonga John M , Murungi Lucy K , Baidu-Forson Joseph J , Abukutsa-Onyango Mary O 
Published: September 2019

AbstractAmaranth (Amaranthus L.) species are grown for their grain or leaves and contribute to farmers’ livelihoods and nutritional food security. Leafy amaranth (LA) is consumed widely as a vegetable in Kenya. An assessment of current farmers’ knowledge of pest management practices provides information about future educational needs. Six-hundred LA farmers were interviewed, focus group discussions with farmers, and interviews with key informants were completed in four Kenyan counties. The majority (71%) of survey respondents grew LA on less than 0.25 acre (<0.1 ha) and 59.2% were female. Constraints of LA production differed by counties surveyed. Farmers indicated insects and birds were important in Kiambu and Kisumu counties, whereas in Vihiga and Kisii, capital, markets, and land area for production were important. Farmers stated and ranked importance of the insects they observed during LA production. Eighty-seven percent stated aphids (Hemiptera: Aphididae), as a major pest and 96.8% ranked aphids as the number-one insect pest of LA in all four counties. Two other pests of LA included cotton leafworm, Spodoptera littoralis (Lepidoptera: Noctuidae) (0.8%) and spider mites, Tetranychus spp (Trombidiformes; Tetranychidae) (0.7%). Forty-two percent of all LA farmers managed aphids, with 34% using synthetic insecticides and 8% using nonsynthetic methods. Biological controls and host-plant resistance were not mentioned. Educational programs that train farmers about integrated pest management (IPM) in LA production are needed. Future research should determine successful IPM strategies for aphids on LA to reduce insecticide use and improve sustainability and nutritional food security for small-landholder farmers and consumers.
Is Guyana a new oil El Dorado?
Authors: Panelli Luis Fernando 
Published: September 2019

Abstract
The Co-operative Republic of Guyana has become one of the most interesting and dynamic oil producing countries in the world at the start of the 21st century. The country already holds 5 billion barrels of proved reserves, which will certainly grow with new discoveries. Exxon leads a consortium of four companies that have the concession of the Stabroek Block (Liza Field), where nine discoveries have been made so far. Five FPSOs will be operating in the future, one of which is due to arrive in Guyana before the end of 2019 and another is due for 2020. By then, the country will be producing 340,000 barrels a day. This production will double and then reach 1 million barrels a day before the end of the next decade. The challenges and opportunities regarding the Guyanese people are dire. The lack of proper infrastructure is certainly one of the biggest challenges. But it is important to stress that the oil proceeds will transform Guyana into the highest GDP per capita of South America. The political stage is also analysed, since political instability might raise concerns for long-term investors. The Venezuela–Guyana differences regarding the sovereignty of the Essequibo Region are again a cause for concern. Brazil is a key player in supporting the geopolitical stability of South America. Presidential elections will be held in 2019/2020: the dispute will probably be between the current President Granger and the Opposition candidate Irfaan Ali. Guyana has a lot to profit from the wealth brought by oil exploitation, but its people fear the risk of growing corruption.
Clinical Use of κ Free Light Chains Index as a Screening Test for Multiple Sclerosis
Authors: Agnello Luisa , Lo Sasso Bruna , Salemi Giuseppe , Altavilla Patrizia , Pappalardo Emanuela Maria , Caldarella Rosalia , Meli Francesco , Scazzone Concetta , Bivona Giulia , Ciaccio Marcello 
Published: September 2019

Abstract

Objective
To assess the usefulness of the κ free light chain index (κFLCi) as a screening test to identify patients with suspected MS.

Methods
The study included 56 patients with a request to test for oligoclonal bands (OCBs). OCBs were detected by isoelectric focusing, followed by immunofixation. Cerebrospinal fluid (CSF) and serum κFLC were measured by a turbidimetric assay. Also, the κFLC index (κFLCi) was calculated.

Results
CSF κFLC levels and κFLCi were significantly higher in patients with multiple sclerosis (MS) than in patients with other neurological diseases (NDs; P &lt; .001 and P &lt; .001, respectively). At the cutoff value of 2.9, the κFLCi detected MS with sensitivity of 97% and specificity of 65%. Overall, 92% patients with κFLCi of 2.9 or greater and who had tested positive for OCBs were diagnosed as having MS.

Conclusion
Our findings support the use of κFLCi as a screening test when MS is suspected, followed by OCB detection as a confirmatory test for the diagnosis of MS.
The (Un)Making of a History Book: Revisiting the Earliest Manuscripts of Eadmer of Canterbury’s Historia novorum in Anglia*
Authors: Pohl Benjamin 
Published: September 2019

Abstract
This article revisits the earliest manuscripts of the ‘History of Recent Events in England’ (Historia novorum in Anglia) written by Eadmer of Canterbury during the first decades of the twelfth century. Today, it is widely recognised as one of the most important pieces of historical writing produced in England during the period following the Norman Conquest. The article is the first in over twenty years to offer an in-depth codicological study of the Historia novorum’s principal manuscripts, and it provides a critical corrective to the canonical studies of Richard Southern (1963/90), whose arguments still form the communis opinio in present-day scholarship. Analysis shows that, contrary to established scholarly consensus, Eadmer did not compose his work in two distinct versions separated by a five-year writing hiatus, but that he kept writing continuously and produced one or more interim redactions of the Historia novorum that continued the narrative up to key moments in the history of early twelfth-century England.
The young stellar population of the metal-poor galaxy NGC 6822
Authors: Jones Olivia C , Sharp Michael J , Reiter Megan , Hirschauer Alec S , Meixner M , Srinivasan Sundar 
Published: September 2019

ABSTRACT
We present a comprehensive study of massive young stellar objects (YSOs) in the metal-poor galaxy NGC 6822 using IRAC and MIPS data obtained from the Spitzer Space Telescope. We find over 500 new YSO candidates in seven massive star formation regions; these sources were selected using six colour–magnitude cuts. Via spectral energy distribution fitting to the data with YSO radiative transfer models we refine this list, identifying 105 high-confidence and 88 medium-confidence YSO candidates. For these sources, we constrain their evolutionary state and estimate their physical properties. The majority of our YSO candidates are massive protostars with an accreting envelope in the initial stages of formation. We fit the mass distribution of the Stage I YSOs with a Kroupa initial mass function and determine a global star formation rate of 0.039 $\mathrm{M}_{\odot } \, \mathrm{yr}^{-1}$. This is higher than star formation rate estimates based on integrated UV fluxes. The new YSO candidates are preferentially located in clusters which correspond to seven active high-mass star-formation regions which are strongly correlated with the 8 and 24 μm emission from PAHs and warm dust. This analysis reveals an embedded high-mass star formation region, Spitzer I, which hosts the highest number of massive YSO candidates in NGC 6822. The properties of Spitzer I suggest it is younger and more active than the other prominent H ii and star-formation regions in the galaxy.
The excitation of NH2 in the interstellar medium
Authors: Bouhafs N , Bacmann A , Faure A , Lique F 
Published: September 2019

ABSTRACT
Accurate estimation of the abundance of the NH2 radical in the interstellar medium requires accurate radiative and collisional rate coefficients. The calculation of hyperfine-resolved rate coefficients for the collisional (de-)excitation of NH2 by both ortho- and para-H2 is presented in this work. Hyperfine-resolved rate coefficients are calculated from pure rotational close-coupling rate coefficients using the Mj randomizing approximation. Rate coefficients for temperatures ranging from 5 to 150 K were computed for all hyperfine transitions among the first 15 rotational energy levels of both ortho- and para-NH2 in collisions with ortho- and para-H2. The new data were then employed in radiative transfer calculations to simulate the excitation of NH2 in typical star-forming regions such as W31C, where NH2 is seen in emission. We compared the excitation and brightness temperatures for different NH2 transitions obtained using the new and the previously available collisional data. It is found that the new rate coefficients increase the simulated line intensities by a factor ∼10–30. As a consequence, NH2 abundance derived from the observations will be significantly reduced by the use of the present rate coefficients.
Constraints on the production and escape of ionizing radiation from the emission-line spectra of metal-poor star-forming galaxies
Authors: Plat A , Charlot S , Bruzual G , Feltre A , Vidal-García A , Morisset C , Chevallard J , Todt H 
Published: September 2019

ABSTRACT
We explore the production and escape of ionizing photons in young galaxies by investigating the ultraviolet and optical emission-line properties of models of ionization-bounded and density-bounded H ii regions, active-galactic-nucleus (AGN) narrow-line regions, and radiative shocks computed all using the same physically consistent description of element abundances and depletion on to dust grains down to very low metallicities. We compare these models with a reference sample of metal-poor star-forming galaxies and Lyman-continuum (LyC) leakers at various redshifts, which allows the simultaneous exploration of more spectral diagnostics than typically available at once for individual subsamples. We confirm that current single- and binary-star population synthesis models do not produce hard-enough radiation to account for the high-ionization emission of the most metal-poor galaxies. Introducing either an AGN or radiative-shock component brings models into agreement with observations. A published model including X-ray binaries is an attractive alternative to reproduce the observed rise in He iiλ4686/H β ratio with decreasing oxygen abundance in metal-poor star-forming galaxies, but not the high observed He iiλ4686/Hβ ratios of galaxies with large EW(Hβ). A source of harder ionizing radiation appears to be required in these extreme objects, such as an AGN or radiative-shock component, perhaps linked to an initial-mass-function bias towards massive stars at low metallicity. This would also account for the surprisingly high [O i]/[O iii] ratios of confirmed LyC leakers relative to ionization-bounded models. We find no simple by-eye diagnostic of the nature of ionizing sources and the escape of LyC photon, which require proper simultaneous fits of several lines to be discriminated against.
The peculiar chemistry of the inner ejecta of Eta Carina
Authors: Bordiu Cristobal , Rizzo J Ricardo 
Published: September 2019

ABSTRACT
We investigated continuum and molecular line emission of four species (CO, HCN, H13CN, and HCO+) at 0.8 mm in the inner region around η Car, using ALMA archival observations at a resolution better than 0.2 arcsec. We report the discovery of an asymmetric extended structure north-west of the star, independent from the continuum point source. The structure is only traced by continuum and HCO+, and not detected in the other lines. Kinematics of this structure reveal that the HCO+ gas likely arises from ejecta expelled in the 1890s eruption. The ejecta is propagating outwards within the cavity produced by the current wind–wind interaction of η Car A and its companion. Chemical analysis of the ejecta reveals an apparent lack of CO and nitrogen-bearing species. We explore possible explanations for this peculiar chemistry, that differentiates this structure from the ejecta of the Great Eruption, rich in HCN and H13CN. We also report an absorption component near the continuum point source, only traced by HCN and H13CN in their vibrational-ground and vibrationally excited states. This absorbing gas is attributed to a hot bullet of N-enriched material expelled at a projected velocity of 40 km s−1.
Substrate conformational dynamics facilitate structure-specific recognition of gapped DNA by DNA polymerase
Authors: Craggs Timothy D , Sustarsic Marko , Plochowietz Anne , Mosayebi Majid , Kaju Hendrik , Cuthbert Andrew , Hohlbein Johannes , Domicevica Laura , Biggin Philip C , Doye Jonathan P K , Kapanidis Achillefs N 
Published: September 2019

Abstract
DNA-binding proteins utilise different recognition mechanisms to locate their DNA targets; some proteins recognise specific DNA sequences, while others interact with specific DNA structures. While sequence-specific DNA binding has been studied extensively, structure-specific recognition mechanisms remain unclear. Here, we study structure-specific DNA recognition by examining the structure and dynamics of DNA polymerase I Klenow Fragment (Pol) substrates both alone and in DNA–Pol complexes. Using a docking approach based on a network of 73 distances collected using single-molecule FRET, we determined a novel solution structure of the single-nucleotide-gapped DNA–Pol binary complex. The structure resembled existing crystal structures with regards to the downstream primer-template DNA substrate, and revealed a previously unobserved sharp bend (∼120°) in the DNA substrate; this pronounced bend was present in living cells. MD simulations and single-molecule assays also revealed that 4–5 nt of downstream gap-proximal DNA are unwound in the binary complex. Further, experiments and coarse-grained modelling showed the substrate alone frequently adopts bent conformations with 1–2 nt fraying around the gap, suggesting a mechanism wherein Pol recognises a pre-bent, partially-melted conformation of gapped DNA. We propose a general mechanism for substrate recognition by structure-specific enzymes driven by protein sensing of the conformational dynamics of their DNA substrates.
Determinism and Obligation
Authors: Haji Ishtiyaque 
Published: September 2019

Abstract
Chapter 2 addresses the deterministic horn. Whether determinism threatens obligation turns partly but pivotally on whether the alternatives obligation requires are of the sort that one can have even if determinism is true (weak alternatives) or of the sort determinism precludes one from having (strong alternatives). A line of reasoning for the view that obligation presupposes only that that agents have weak alternatives is evaluated. The chapter concludes with the argument that even if a teleological account of reasons explanation, according to which actions are to be explained in terms of the goals of agents and not in terms of whether they are caused by appropriate mental items (or their neural realizers), is true, determinism still threatens obligation if obligation requires strong alternatives.
The Extended Luck Problem
Authors: Haji Ishtiyaque 
Published: September 2019

Abstract
Chapter 4 continues critical discussion of the cross-world or present luck problem regarding obligation. It assesses various responses to this problem, including responses by teleological theorists about action explanation, agent causalists, and event causalists. It evaluates the view that so-called non-action-centered varieties of libertarianism (as opposed to action-centered varieties) bypass this objection. It discusses why the phenomenon of “tracing” with respect to obligation—the freedom of an action that is obligatory may be inherited from a previously performed free action—is not promising. It argues, finally, that this sort of luck objection is far reaching. It affects non-moral varieties of obligation, such as prudential obligation, and extends to best-from-one’s-own-point-of-view judgments that play a vital role in our practical deliberations.
Enfranchised
Authors: Andreas Joel 
Published: September 2019

AbstractChapter 2 recounts how the Chinese Communist Party reorganized industrial enterprises after taking power in 1949. Small numbers of party cadres, typically peasant veterans of the rural insurgency, were dispatched to factories to mobilize workers to attack capitalists and incumbent managers. Through a series of aggressive mass campaigns, the party established its control, recruiting workers to serve as factory leaders and creating party-led institutions of participation. After nationalization was completed in 1956, Mao—concerned that Communist cadres were becoming autocratic and arrogant—initiated a Party Rectification campaign, in which he encouraged unusually freewheeling criticism of “bureaucratism” among party officials. This opening unleashed a torrent of criticism by intellectuals as well as strikes by workers and inspired union leaders to push for greater independence from the party. The campaign, however, was quickly aborted and during the subsequent Anti-Rightist movement those who had spoken out were harshly punished, squelching prospects for autonomous activity.
Participatory Paternalism
Authors: Andreas Joel 
Published: September 2019

AbstractChapter 3 describes the institutional foundations of the Chinese work unit system and the practices of worker participation in the early 1960s, after the system was fully established and before the onset of the Cultural Revolution. Participatory institutions included self-managing teams on the shop floor, technical innovation groups, factory elections, representative congresses, and other mechanisms designed to solicit suggestions from below, learn about and defuse employees’ grievances and concerns, and mobilize workers to monitor and criticize factory leaders. Despite high levels of participation, predicated on lifetime job tenure and relatively egalitarian distribution, industrial governance was democratic only in a very limited sense. The party insisted on maintaining a political monopoly and harshly suppressed any hint of independent political activity. Not only was the scope of workers’ influence restricted largely to the shop floor, but they also had little autonomy. Although participation was extensive, the system was more paternalistic than democratic.