bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emerging technologies for cystic fibrosis transmembrane conductance regulator restoration in all people with CF
Authors: Egan Marie E. 
Published: July 2020

AbstractAlthough effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy has the potential to change the lives of many patients with cystic fibrosis (CF), it is unlikely that these drugs will be a game changing therapy for all. There are about 10% of patients with CF who don't produce a mutant protein tomodulate, potentiate, or optimize and for these patients such therapies are unlikely to be of significant benefit. There is a need to develop new therapeutic approaches that can work for this patient population and can advance CF therapies. These new therapies will be genetic‐based therapies and each approach will result in functional CFTR protein inpreviously affected CF cells. In this review we will examine the potential of RNA therapies, gene transfer therapies, and gene editing therapies for the treatment of CF as well as the challenges that will need to be facedas we harness the power of these emerging therapies towards a one‐time cure.
Evaluation of ice particle growth in ICON using statistics of multi‐frequency Doppler cloud radar observations
Authors: Ori Davide , Schemann Vera , Karrer Markus , Dias Neto José , von Terzi Leonie , Seifert Axel , Kneifel Stefan 
Published: July 2020

AbstractVertically pointing radar observations combining multiple frequencies and Doppler measurements have been recently shown to contain valuable information about ice particle growth processes, such as aggregation and riming. In this study, we use a two‐months X, Ka, W‐Band Doppler radar dataset of midlatitude winter clouds to infer statistical growth signatures of ice and snow particles. The observational statistics are compared to forward‐simulated radar moments based on simulations of the campaign time period with a high‐resolution version of the ICON model and a two‐moment microphysical scheme. The statistical comparison shows very good agreement of the simulated vertical structure of radar reflectivity and surface precipitation rate. The dual‐wavelength ratios, which are closely related to the mean particle size, also show consistently a major increase at temperatures higher than –15 °C. However, at temperatures higher than –7 °C, ICON increasingly overestimates the mean particle size. The statistics of mean Doppler velocities also reveal that the model overestimates the terminal velocity of snow particles, especially at larger sizes. We discuss possible reasons for the identified discrepancies, such as an unrealistic temperature dependence of the sticking efficiency or the non‐saturation of terminal velocities at larger sizes caused by the implemented power law relations. Our study demonstrates examples of the importance of combining various radar techniques for identifying issues in simulated microphysical processes, which can otherwise be hidden due to compensating errors.
Antecedents and consequences of knowledge sharing for software process improvement in the Indian software industry
Authors: Chugh Mitali , Chanderwal Nitin , Upadhyay Rajesh Kumar , Punia Devendra Kumar 
Published: July 2020

AbstractThe integration of knowledge sharing is significant for software process improvement (SPI). However, very few empirical studies have evaluated how and to what extent knowledge sharing affects the different aspects of SPI. Drawing upon the resource‐based view and the knowledge‐based view of software development organizations, we have explored the antecedents and consequences of knowledge sharing for SPI success. This study develops and empirically validates a model presenting how knowledge sharing impacts SPI success, how organizational factors (leadership and trust) and an individual factor (motivation) affect knowledge sharing and how the use of information technology facilitates explicitly the relation between knowledge sharing and SPI success. The empirical testing of the model has been carried out using the statistical technique of structural equation modelling (SEM) by analysing the dataset of 556 respondents collected from Indian software development organizations. The outcomes reveal that knowledge sharing enhances SPI in terms of design effectiveness, lesser fault density and improved software development competence. Also, the results show that the use of information technology moderates the relation of knowledge sharing and SPI. The conclusions also contribute to improving our knowledge about how leadership, trust and motivation drive efficient knowledge sharing on the path to SPI success.
Phylogeny of Acanthophyllum s.l. revisited: An update on generic concept and sectional classification
Authors: Pirani Atefeh , Moazzeni Hamid , Zarre Shahin , Rabeler Richard K. , Oxelman Bengt , Pavlenko Alexander V. , Kovalchuk Andriy 
Published: July 2020

AbstractThe generic boundary of the broadly defined Acanthophyllum s.l., the third‐largest genus of the tribe Caryophylleae (Caryophyllaceae), has been a subject of taxonomic confusion. Acanthophyllum s.l. now includes five minor genera previously recognized as independent. Among these small genera, the inclusion of Allochrusa, Ochotonophila, and Scleranthopsis within Acanthophyllum s.l. was confirmed by previous molecular studies, while the positions of Diaphanoptera and Kuhitangia remained uncertain. We have performed an updated molecular study of Acanthophyllum s.l. including an increased sampling of the genera and sections assigned to this group, using intron sequences of the chloroplast gene rps16 and nuclear ribosomal internal transcribed spacer (ITS) sequences. Cyathophylla, Heterochroa, and Saponaria were chosen as outgroups for performing phylogenetic analyses using maximum likelihood and Bayesian methods. The present results suggest that, in addition to the genera mentioned above, both Diaphanoptera and Kuhitangia should also be synonymized within Acanthophyllum. Sections Diaphanoptera, Kuhitangia and Pseudomacrostegia are introduced as new infrageneric taxa within Acanthophyllum. Our results also indicate that some annual species of Saponaria are closely related to Acanthophyllum.
Nano nickel oxide promotes epithelial‐mesenchymal transition through transforming growth factor β1/smads signaling pathway in A549 cells
Authors: Chang Xuhong , Tian Minmin , Zhang Qiong , Gao Jinxia , Li Sheng , Sun Yingbiao 
Published: July 2020

AbstractOur previous study demonstrated that nano nickel oxide (NiO) induce pulmonary fibrosis in rats and collagen excessive formation in A549 cells, which mechanism was related with the increasing transforming growth factor β1 (TGF‐β1) secretion. However, it remains unclear understanding the role of TGF‐β1 in collagen excessive formation. Here, we found nano NiO could directly promote epithelial‐mesenchymal transition (EMT) via the TGF‐β1/Smads pathway in A549 cells. First, cytotoxicity induced by nano NiO has a dose‐ and time‐dependent manner according to methylthiaozol tetrazolium assay. Second, nano NiO led to the increased contents of type I collagen (Col‐I), TGF‐β1, p‐Smad2, p‐Smad3, alpha‐smooth muscle actin (α‐SMA), vimentin, and fibronectin, indicating Smads pathway activation and EMT occurence. Third, to verify whether TGF‐β1 activated Smads signaling pathway and EMT occurence, A549 cells were exposed to nano NiO and TGF‐β1 inhibitors (10 μM SB431542). The results showed that TGF‐β1 inhibitors alleviated the nano NiO‐induced cytotoxicity and Col‐I excessive formation. Meanwhile, TGF‐β1 inhibitors reversed the proteins expression trends of Col‐I, p‐Smad2, p‐Smad3, α‐SMA, vimentin, fibronectin, and E‐cadherin. These observations suggested that EMT occurrence via TGF‐β1/Smads pathway might play an important role in the collagen excessive formation induced by nano NiO in A549 cells.
Two-point functions at arbitrary genus and its resurgence structure in a matrix model for 2D type IIA superstrings
Authors: Kuroki Tsunehide 
Published: July 2020

AbstractIn the previous papers, it is pointed out that a supersymmetric double-well matrix model corresponds to a two-dimensional type IIA superstring theory on a Ramond-Ramond background at the level of correlation functions. This was confirmed by agreement between their planar correlation functions. The supersymmetry in the matrix model corresponds to the target space supersymmetry and it is shown to be spontaneously broken by nonperturbative effect. Furthermore, in the matrix model we computed one-point functions of single-trace operators to all order of genus expansion in its double scaling limit. We found that this expansion is stringy and not Borel summable and hence there arises an ambiguity in applying the Borel resummation technique. We confirmed that resurgence works here, namely this ambiguity in perturbative series in a zero-instanton sector is exactly canceled by another ambiguity in a one-instanton sector obtained by instanton calculation. In this paper we extend this analysis and study resurgence structure of the two-point functions of the single trace operators. By using results in the random matrix theory, we derive two-point functions at arbitrary genus and see that the perturbative series in the zero-instanton sector again has an ambiguity. We find that the two-point functions inevitably have logarithmic singularity even at higher genus. In this derivation we obtain a new result of the two-point function expressed by the one-point function at the leading order in the soft-edge scaling limit of the random matrix theory. We also compute an ambiguity in the one-instanton sector by using the Airy kernel, and confirm that ambiguities in both sectors cancel each other at the leading order in the double scaling limit. We thus clarify resurgence structure of the two-point functions in the supersymmetric double-well matrix model.
Curing Velocity Superselection in Non-relativistic QED by Restriction to a Lightcone
Authors: Cadamuro Daniela , Dybalski Wojciech 
Published: July 2020

AbstractIt is physically expected that plane-wave configurations of the electron in QED induce disjoint representations of the algebra of the electromagnetic fields. This phenomenon of velocity superselection, which is one aspect of the infrared problem, is mathematically well established in non-relativistic (Pauli–Fierz type) models of QED. We show that velocity superselection can be resolved in such models by restricting the electron states to the subalgebra of the fields localized in the future lightcone. This actually follows from a more general statement about equivalence of GNS representations for coherent states of the algebra of the future lightcone in free electromagnetism. Our analysis turns out to be meaningful in the non-relativistic setting and provides evidence in favour of the Buchholz–Roberts approach to infrared problems.
Phenotypic characterisation and linkage mapping of domestication syndrome traits in yellow lupin (Lupinus luteus L.)
Authors: Iqbal Muhammad Munir , Erskine William , Berger Jens D. , Nelson Matthew N. 
Published: July 2020

AbstractThe transformation of wild plants into domesticated crops usually modifies a common set of characters referred to as ‘domestication syndrome’ traits such as the loss of pod shattering/seed dehiscence, loss of seed dormancy, reduced anti-nutritional compounds and changes in growth habit, phenology, flower and seed colour. Understanding the genetic control of domestication syndrome traits facilitates the efficient transfer of useful traits from wild progenitors into crops through crossing and selection. Domesticated forms of yellow lupin (Lupinus luteus L.) possess many domestication syndrome traits, while their genetic control remains a mystery. This study aimed to reveal the genetic control of yellow lupin domestication traits. This involved phenotypic characterisation of those traits, defining the genomic regions controlling domestication traits on a linkage map and performing a comparative genomic analysis of yellow lupin with its better-understood relatives, narrow-leafed lupin (L. angustifolius L.) and white lupin (L. albus L.). We phenotyped an F9 recombinant inbred line (RIL) population of a wide cross between Wodjil (domesticated) × P28213 (wild). Vernalisation responsiveness, alkaloid content, flower and seed colour in yellow lupin were each found to be controlled by single loci on linkage groups YL-21, YL-06, YL-03 and YL-38, respectively. Aligning the genomes of yellow with narrow-leafed lupin and white lupin revealed well-conserved synteny between these sister species (76% and 71%, respectively). This genomic comparison revealed that one of the key domestication traits, vernalisation-responsive flowering, mapped to a region of conserved synteny with the vernalisation-responsive flowering time Ku locus of narrow-leafed lupin, which has previously been shown to be controlled by an FT homologue. In contrast, the loci controlling alkaloid content were each found at non-syntenic regions among the three species. This provides a first glimpse into the molecular control of flowering time in yellow lupin and demonstrates both the power and the limitation of synteny as a tool for gene discovery in lupins.
Innovation, institutional ownership and financial constraints
Authors: Schain Jan Philip , Stiebale Joel 
Published: July 2020

AbstractWe analyze the relationship between institutional investors, innovation and financing constraints. Using the same dataset as Aghion et al. (Am Econ Rev 103(1):277–304, 2013), we find that the effect of institutional ownership on innovation is concentrated in industries with high dependence on external finance and among firms which are a priori likely to be financially constrained. The complementarity between institutional ownership and competition, predicted by the original paper’s theory where institutional investors increase innovation through reducing career risks, disappears once this heterogeneity is taken into account. We also provide evidence that the sensitivity of R&D investment to internal funds decreases with institutional ownership.
The role of demand in fostering product vs process innovation: a model and an empirical test
Authors: Dawid Herbert , Pellegrino Gabriele , Vivarelli Marco 
Published: July 2020

AbstractWhile the extant innovation literature has provided extensive evidence of the so-called “demand-pull” effect, the possible diverse impact of demand evolution on product vs process innovation activities has not been yet investigated. This paper develops a formal model predicting a larger inducing impact of past sales in fostering product rather than process innovation. This prediction is then tested through a dynamic microeconometric model, controlling for R&D persistence, sample selection, observed and unobservable individual firm effects and time and sectoral peculiarities. Results are consistent with the model and suggest that an expansionary economic policy may benefit the diffusion of new products or even the emergence of entire new sectors.
Characterization of the genes responsible for rubber degradation in Actinoplanes sp. strain OR16
Authors: Gibu Namiko , Arata Tomoka , Kuboki Saya , Linh Dao Viet , Fukuda Masao , Steinbüchel Alexander , Kasai Daisuke 
Published: July 2020

AbstractA Gram-positive rubber-degrading bacterium, Actinoplanes sp. strain OR16 (strain NBRC 114529), is able to grow on agar plates containing natural and synthetic rubber as the sole sources of carbon and energy. When this strain was grown on natural rubber latex overlay agar plates, translucent halos around the cells were observed. To identify the natural rubber degradation genes and other features of its metabolism, its complete genome sequence was determined. The genome of OR16 consists of 9,293,892 bp and comprises one circular chromosome (GenBank accession number AP019371.1) with a G + C content of 70.3%. The genome contains 8238 protein-coding and 18 rRNA genes. A homology search of the genome sequence revealed that three genes (lcp1, lcp2, and lcp3) are homologous to an extracellular latex-clearing protein (Lcp) of Streptomyces sp. K30. RT-PCR analysis revealed that lcp1 and lcp2 seem to constitute an operon. Purified lcp gene products have oxygen consumption activity toward natural rubber latex, suggesting that all these genes encode rubber-degrading enzymes in OR16. Quantitative reverse transcription-PCR analysis indicated that the transcription of these genes is induced during the growth of OR16 on natural rubber. The genes located adjacent to lcp1 and lcp3, which code for a TetR/AcrR-type transcriptional regulator, can bind to the promoter regions of these lcp genes. It is suggested that the putative regulators play a role in regulating the transcription of the lcp genes. These results strongly suggested that three lcp genes are required for the utilization of natural rubber in strain OR16.

Key Points• The complete genome sequence of Actinoplanes sp. strain OR16 was determined.• Three lcp genes which are involved in the natural rubber degradation in OR16 were identified.• Transcription of these lcp genes is induced during utilization of rubber in OR16.• Two regulators, which bind to the promoter regions of lcp, were determined.
Clinical impact of follicular oncocytic (Hürthle cell) carcinoma in comparison with corresponding classical follicular thyroid carcinoma
Authors: Wenter Vera , Albert Nathalie L. , Unterrainer Marcus , Ahmaddy Freba , Ilhan Harun , Jellinek Annamirl , Knösel Thomas , Bartenstein Peter , Spitzweg Christine , Lehner Sebastian , Todica Andrei 
Published: July 2020

Abstract
Purpose
There are controversial debates if patients with Hürthle cell carcinoma, also known as oxyphilic or oncocytic cell follicular thyroid carcinoma, have a poorer outcome. In this study, we systematically evaluated the clinical outcome in a large patient cohort following thyroidectomy and initial I-131 radioactive iodine therapy (RIT).

Methods
We retrospectively evaluated a total of 378 patients with diagnosed oncocytic follicular Hürthle cell carcinoma (OFTC) (N = 126) or with classical follicular thyroid carcinoma (FTC) (N = 252). Patients received thyroidectomy and complementary I-131 RIT. Clinical data regarding basic demographic characteristics, tumor grade, persistent disease and recurrence during follow-up, and disease-free, disease-specific, and overall survival were collected during follow-up of 6.9 years (interquartile range 3.7; 11.7 years). Univariate and multivariate analyses were used to identify factors associated with disease-related and overall survival.

Results
Before and after matching for risk factors, recurrence was significantly more frequently diagnosed in OFTC patients during follow-up (17% vs. 8%; p value 0.037). Likewise, OFTC patients presented with a reduced mean disease-free survival of 17.9 years (95% CI 16.0–19.8) vs. 20.1 years (95% CI 19.0–21.1) in FTC patients (p value 0.027). Multivariate analysis revealed OFTC (HR 0.502; 95% CI 0.309–0.816) as the only independent prognostic factor for disease-free survival. Distant metastases of OFTC patients were significantly less iodine-avid (p value 0.014). Mean disease-specific and overall survival did not differ significantly (p value 0.671 and 0.687) during follow-up of median 6.9 years (3.7; 11.7 years).

Conclusions
Our study suggests that recurrence is more often seen in OFTC patients. OFTC patients have a poorer prognosis for disease-free survival. Thus, OFTC and FTC behave differently and should be categorized separately. However, patients suffering from OFTC present with the same overall and disease-specific survival at the end of follow-up indifferent to FTC patients after initial RIT.
Myocardial creep-induced misalignment artifacts in PET/MR myocardial perfusion imaging
Authors: von Felten Elia , Benetos Georgios , Patriki Dimitri , Benz Dominik C. , Rampidis Georgios P. , Giannopoulos Andreas A. , Bakula Adam , Gräni Christoph , Pazhenkottil Aju P. , Gebhard Catherine , Fuchs Tobias A. , Kaufmann Philipp A. , Buechel Ronny R. 
Published: July 2020

Abstract
Purpose
Misalignment between positron emission tomography (PET) datasets and attenuation correction (AC) maps is a potential source of artifacts in myocardial perfusion imaging (MPI). We assessed the impact of adenosine on the alignment of AC maps derived from magnetic resonance (MR) and PET datasets during MPI on a hybrid PET/MR scanner.

Methods
Twenty-eight volunteers underwent adenosine stress and rest 13N-ammonia MPI on a PET/MR. We acquired Dixon sequences for the creation of MRAC maps. After reconstruction of the original non-shifted PET images, we examined MRAC and PET datasets for cardiac spatial misalignment and, if necessary, reconstructed a second set of shifted PET images after manually adjusting co-registration. Summed rest, stress, and difference scores (SRS, SSS, and SDS) were compared between shifted and non-shifted PET images. Additionally, we measured the amount of cranial movement of the heart (i.e., myocardial creep) after termination of adenosine infusion.

Results
Realignment was necessary for 25 (89.3%) stress and 12 (42.9%) rest PET datasets. Median SRS, SSS, and SDS of the non-shifted images were 6 (IQR = 4–7), 12 (IQR = 7–18), and 8 (IQR = 2–11), respectively, and of the shifted images 2 (IQR = 1–6), 4 (IQR = 7–18), and 1 (IQR = 0–2), respectively. All three scores were significantly higher in non-shifted versus shifted images (all p < 0.05). The difference in SDS correlated moderately but significantly with the amount of myocardial creep (r = 0.541, p = 0.005).

Conclusion
Misalignment of MRAC and PET datasets commonly occurs during adenosine stress MPI on a hybrid PET/MR device, potentially leading to an increase in false-positive findings. Our results suggest that myocardial creep may substantially account for this and prompt for a careful review and correction of PET/MRAC data.
Feed-forward neural networks using cerebral MR spectroscopy and DTI might predict neurodevelopmental outcome in preterm neonates
Authors: Janjic T. , Pereverzyev S. , Hammerl M. , Neubauer V. , Lerchner H. , Wallner V. , Steiger R. , Kiechl-Kohlendorfer U. , Zimmermann M. , Buchheim A. , Grams A. E. , Gizewski E. R. 
Published: July 2020

AbstractObjectivesWe aimed to evaluate the ability of feed-forward neural networks (fNNs) to predict the neurodevelopmental outcome (NDO) of very preterm neonates (VPIs) at 12 months corrected age by using biomarkers of cerebral MR proton spectroscopy (1H-MRS) and diffusion tensor imaging (DTI) at term-equivalent age (TEA).MethodsIn this prospective study, 300 VPIs born before 32 gestational weeks received an MRI scan at TEA between September 2013 and December 2017. Due to missing or poor-quality spectroscopy data and missing neurodevelopmental tests, 173 VPIs were excluded. Data sets consisting of 103 and 115 VPIs were considered for prediction of motor and cognitive developmental delay, respectively. Five metabolite ratios and two DTI characteristics in six different areas of the brain were evaluated. A feature selection algorithm was developed for receiving a subset of characteristics prevalent for the VPIs with a developmental delay. Finally, the predictors were constructed employing multiple fNNs and fourfold cross-validation.ResultsBy employing the constructed fNN predictors, we were able to predict cognitive delays of VPIs with 85.7% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 99.1% negative predictive value (NPV). For the prediction of motor delay, we achieved a sensitivity of 76.9%, a specificity of 98.9%, a PPV of 90.9% and an NPV of 96.7%.ConclusionFNNs might be able to predict motor and cognitive development of VPIs at 12 months corrected age when employing biomarkers of cerebral1H-MRS and DTI quantified at TEA.Key Points• A feed-forward neuronal network is a promising tool for outcome prediction in premature infants.• Cerebral proton magnetic resonance spectroscopy and diffusion tensor imaging can be used for the construction of early prognostic biomarkers.• Premature infants that would most benefit from early intervention services can be spotted at the time of optimal neuroplasticity.