bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of Drug‐Like Protein–Protein Interaction Stabilizers Guided By Chelation‐Controlled Bioactive Conformation Stabilization
Authors: Bosica Francesco , Andrei Sebastian A. , Neves João Filipe , Brandt Peter , Gunnarsson Anders , Landrieu Isabelle , Ottmann Christian , O'Mahony Gavin 
Published: April 2020

AbstractProtein–protein interactions (PPIs) of 14‐3‐3 proteins are a model system for studying PPI stabilization. The complex natural product Fusicoccin A stabilizes many 14‐3‐3 PPIs but is not amenable for use in SAR studies, motivating the search for more drug‐like chemical matter. However, drug‐like 14‐3‐3 PPI stabilizers enabling such studies have remained elusive. An X‐ray crystal structure of a PPI in complex with an extremely low potency stabilizer uncovered an unexpected non‐protein interacting, ligand‐chelated Mg2+ leading to the discovery of metal‐ion‐dependent 14‐3‐3 PPI stabilization potency. This originates from a novel chelation‐controlled bioactive conformation stabilization effect. Metal chelation has been associated with pan‐assay interference compounds (PAINS) and frequent hitter behavior, but chelation can evidently also lead to true potency gains and find use as a medicinal chemistry strategy to guide compound optimization. To demonstrate this, we exploited the effect to design the first potent, selective, and drug‐like 14‐3‐3 PPI stabilizers.
Synthesis of 9‐(6‐Deoxy‐α‐L‐Talofuranosyl)‐6‐Methylpurine and 9‐(6‐Deoxy‐β‐D‐Allofuranosyl)‐6‐Methylpurine Nucleosides
Authors: Hassan Abdalla E. A. , Abou‐Elkhair Reham A. I. , Maaroof Hend M. , Secrist John A. 
Published: April 2020

Abstract6‐Methylpurine (MeP) is a cytotoxic adenine analog that does not exhibit selectivity when administered systemically and could be very useful in a gene therapy approach to cancer treatment involving Escherichia coli purine nucleoside phosphorylase (PNP). 9‐(6‐Deoxy‐β‐D‐allofuranosyl)‐6‐methylpurine [methyl(allo)‐MePR, 18] and 9‐(6‐deoxy‐α‐L‐talofuranosyl)‐6‐methylpurine [methyl(talo)‐MePR, 21] were synthesized as potential prodrugs for MeP in the E. coli PNP/prodrug cancer gene therapy approach. The detailed syntheses of [methyl(allo)‐MePR] and [methyl(talo)‐MePR] are described. The glycosyl donors, 1,2‐di‐O‐acetyl‐3,5‐di‐O‐benzyl‐α‐D‐allofuranose (12) and 1‐O‐acetyl‐3‐O‐benzyl‐2,5‐di‐O‐benzoyl‐α‐L‐talofuranose (16) were prepared from 1,2:5,6‐di‐O‐isopropylidene‐α‐D‐glucofuranose (4) in nine and eleven steps, respectively. Vorbrüggen coupling of the latter glycosyl donors with 6‐methylpurine (3), followed by deprotection of the sugar hydroxyl groups, gave the title compounds in good overall yields. © 2020 by John Wiley & Sons, Inc.Basic Protocol 1: Preparation of 6‐methylpurineBasic Protocol 2: Preparation of the D‐allofuranose derivative (12)Basic Protocol 3: Preparation of 6‐deoxy‐α‐L‐talofuranosideBasic Protocol 4: Preparation of methyl(allo)‐MePR (18)Basic Protocol 5: Preparation of methyl(talo)‐MePR (21)
Genomic prediction for resistance to Fusarium ear rot and fumonisin contamination in maize
Authors: Holland James B. , Marino Thiago P. , Manching Heather C. , Wisser Randall J. 
Published: April 2020

AbstractFusarium ear rot (FER) disease of maize (Zea mays L.) is caused by Fusarium verticillioides (Sacc.) Nirenberg, which produces fumonisin (FUM), a mycotoxin linked to human and animal health risks. Extensive field trials, laborious inoculations and ear evaluations, and expensive antibody assays are required to reliably assess resistances to FER and FUM contamination in breeding populations. To evaluate the potential utility of genomic selection (GS) to improve FER and FUM in maize, we genotyped 6086 single nucleotide polymorphisms (SNPs) on 449 S0:1 lines from a recurrent selection population. Two different partitions of the S0:1 evaluation data were made to test the ability of models trained on 251 or 201 lines evaluated at three locations in 2014–2015 to predict FER and FUM of 198 or 248 different lines evaluated at three locations in 2016. Single‐stage univariate and multivariate genomic best linear unbiased predictor (GBLUP) models and two‐stage GBLUP, Bayes Cπ, Bayesian LASSO, and extreme gradient boosting models were compared for prediction. Maximum prediction accuracy for untested lines in a new year was 0.46 for FER and 0.67 for FUM. Bayesian models optimized for predicting traits influenced by major‐effect loci were best for FUM in one set, despite no evidence for significant individual SNP–trait associations from genome‐wide association study (GWAS) in the training sets; otherwise, GBLUP models were best. These results suggest that GS can help improve resistance to FER and FUM contamination in an applied breeding program.
Tocilizumab treatment in COVID‐19: A single center experience
Authors: Luo Pan , Liu Yi , Qiu Lin , Liu Xiulan , Liu Dong , Li Juan 
Published: April 2020

AbstractTocilizumab (TCZ), a monoclonal antibody against interleukin‐6 (IL‐6), emerged as an alternative treatment for COVID‐19 patients with a risk of cytokine storms recently. In the present study, we aimed to discuss the treatment response of TCZ therapy in COVID‐19 infected patients. The demographic, treatment, laboratory parameters of C‐reactive protein (CRP) and IL‐6 before and after TCZ therapy and clinical outcome in the 15 COVID‐19 patients were retrospectively assessed. Totally 15 patients with COVID‐19 were included in this study. Two of them were moderately ill, six were seriously ill and seven were critically ill. The TCZ was used in combination with methylprednisolone in eight patients. Five patients received the TCZ administration twice or more. Although TCZ treatment ameliorated the increased CRP in all patients rapidly, for the four critically ill patients who received an only single dose of TCZ, three of them (No. 1, 2, and 3) still dead and the CRP level in the rest one patient (No. 7) failed to return to normal range with a clinical outcome of disease aggravation. Serum IL‐6 level tended to further spiked firstly and then decreased after TCZ therapy in 10 patients. A persistent and dramatic increase of IL‐6 was observed in these four patients who failed treatment. TCZ appears to be an effective treatment option in COVID‐19 patients with a risk of cytokine storms. And for these critically ill patients with elevated IL‐6, the repeated dose of the TCZ is recommended.
Optical Coherence Tomography in the Evaluation of the Scalp and Hair: Common Features and Clinical Utility
Authors: Ekelem Chloe , Feil Nate , Csuka Ella , Juhasz Margit , Lin Jessica , Choi Franchesca , Asghari Arya , Heydarlou Dorsa , Mesinkovska Natasha A. 
Published: April 2020

Background and ObjectiveEarly diagnosis and treatment of hair loss disorders is vital in providing patients with improved psychological outcomes. Non‐invasive imaging with optical coherence tomography (OCT) may be useful in characterizing and managing alopecia. Despite expanding clinical applications of OCT in dermatology, guidelines demonstrating in vivo features of normal and alopecic scalp images remain scant. This pilot study aims to provide an atlas of OCT findings of healthy and alopecia subjects, explore diagnostic quantitative endpoints of alopecia, and compare epidermal thickness and follicular density between scalp regions.Study Design/Materials and MethodsA total of 32 patients (19–76 years old) were enrolled in the study, including healthy patients (n = 6), and patients with scarring alopecia (n = 12) or non‐scarring alopecia (n = 14). An in‐line fiber‐based swept source OCT was used to image five scalp locations at baseline and 6‐month visits. Three investigators evaluated each image for gross features, epidermal thickness, and follicular density.ResultsOnly data from baseline imaging analysis is discussed in this manuscript. Qualitative differences of OCT images are identified in sample images from healthy scalp and each subtype of alopecia studied. Scarring alopecia is characterized by significantly increased epidermal thickness (average Image J pixel units 32 ± 2 compared with non‐scarring alopecia [average 28 ± 3] and control [average 27 ± 3]) (P = 0.022) and decreased follicle count (average 35 ± 5 in a 5 × 7 mm2 area compared with control (50 ± 3) and non‐scarring patients (47 ± 6)) (P = 0.0052). Scalp location had no impact on epidermal thickness (P = 0.861) or follicular density (P = 0.15).ConclusionOCT holds promise as a non‐invasive technique to further characterize and objectively measure alopecia. Larger sample sizes and longitudinal data are needed to improve reliability and determine if additional distinction between alopecia subtypes and treatment monitoring is possible. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.
Blue High‐Power Laser Diodes ‐‐ Beam Sources for Novel Applications
Authors: Behringer Martin , König Harald 
Published: April 2020

AbstractHigh‐power diode lasers are possibly the most efficient way of making electrical energy usable for material processing, like welding, cutting, soldering or other high‐power applications. While IR laser were invented over fifty years ago and have been used in industry for more than two decades, GaN high‐power lasers have only recently been used for material processing, especially for welding and soldering of copper. Although the blue wavelength offers unique and undisputable advantages over IR for the latter application, some difficulties still had to be overcome. Here is an overview of the development steps of GaN lasers from their commercial beginnings as a 1 mW light source in Blue‐ray players to today's 1.5 kW system. Also, important investigations to reach power efficiencies of 40 % will be explained as well as considerations to reach lifetimes of 65 khr and longer. We also venture a prediction of future developments based on a comparison to IR laser diodes.
Novel coronavirus infection in children outside of Wuhan, China
Authors: Shen Qinxue , Guo Wei , Guo Ting , Li Jinhua , He Wenlong , Ni Shanshan , Ouyang Xiaoli , Liu Jiyang , Xie Yuanlin , Tan Xin , Zhou Zhiguo , Peng Hong 
Published: April 2020

AbstractBackgroundSince December 8, 2019, an epidemic of coronavirus disease 2019 (COVID‐19) has spread rapidly, but information about children with COVID‐19 is limited.MethodsThis retrospective and the single‐center study were done at the Public Health Clinic Center of Changsha, Hunan, China. We identified all hospitalized children diagnosed with COVID‐19 between January 8, 2019 and February 19, 2020, in Changsha. Epidemiological and clinical data of these children were collected and analyzed. Outcomes were followed until February 26th, 2020.ResultsBy February 19, 2020, nine pediatric patients were identified as having 2019‐nCoV infection in Changsha. Six children had a family exposure and could provide the exact dates of close contact with someone who was confirmed to have 2019‐nCoV infection, among whom the median incubation period was 7.5 days. The initial symptoms of the nine children were mild, including fever (3/9), diarrhea (2/9), cough (1/9), and sore throat (1/9), two had no symptoms. Two of the enrolled patients showed small ground‐glass opacity of chest computed tomography scan. As of February 26, six patients had a negative RT‐PCR for 2019‐nCoV and were discharged. The median time from exposure to a negative RT‐PCR was 14 days.ConclusionsThe clinical symptoms of the new coronavirus infection in children were not typical and showed a less aggressive clinical course than teenage and adult patients. Children who have a familial clustering or have a family member with a definite diagnosis should be reported to ensure a timely diagnosis.
Courant Sigma Model and ‐algebras
Authors: Grewcoe Clay James , Jonke Larisa 
Published: April 2020

AbstractThe Courant sigma model is a 3‐dimensional topological sigma model of AKSZ type which has been used for the systematic description of closed strings in non‐geometric flux backgrounds. In particular, the expression for the fluxes and their Bianchi identities coincide with the local form of the axioms of a Courant algebroid. On the other hand, the axioms of a Courant algebroid also coincide with the conditions for gauge invariance of the Courant sigma model. In this paper we embed this interplay between background fluxes of closed strings, gauge (or more precisely BRST) symmetries of the Courant sigma model and axioms of a Courant algebroid into an ‐algebra structure. We show how the complete BV‐BRST formulation of the Courant sigma model is described in terms of ‐algebras. Moreover, the morphism between the ‐algebra for a Courant algebroid and the one for the corresponding sigma model is constructed.
A Continuum of Evolving De Novo Genes Drives Protein-Coding Novelty in Drosophila
Authors: Heames Brennen , Schmitz Jonathan , Bornberg-Bauer Erich 
Published: April 2020

AbstractOrphan genes, lacking detectable homologs in outgroup species, typically represent 10–30% of eukaryotic genomes. Efforts to find the source of these young genes indicate that de novo emergence from non-coding DNA may in part explain their prevalence. Here, we investigate the roots of orphan gene emergence in the Drosophila genus. Across the annotated proteomes of twelve species, we find 6297 orphan genes within 4953 taxon-specific clusters of orthologs. By inferring the ancestral DNA as non-coding for between 550 and 2467 (8.7–39.2%) of these genes, we describe for the first time how de novo emergence contributes to the abundance of clade-specific Drosophila genes. In support of them having functional roles, we show that de novo genes have robust expression and translational support. However, the distinct nucleotide sequences of de novo genes, which have characteristics intermediate between intergenic regions and conserved genes, reflect their recent birth from non-coding DNA. We find that de novo genes encode more disordered proteins than both older genes and intergenic regions. Together, our results suggest that gene emergence from non-coding DNA provides an abundant source of material for the evolution of new proteins. Following gene birth, gradual evolution over large evolutionary timescales moulds sequence properties towards those of conserved genes, resulting in a continuum of properties whose starting points depend on the nucleotide sequences of an initial pool of novel genes.
Log expansions from combinatorial Dyson–Schwinger equations
Authors: Krüger Olaf 
Published: April 2020

AbstractWe give a precise connection between combinatorial Dyson–Schwinger equations and log expansions for Green’s functions in quantum field theory. The latter are triangular power series in the coupling constant $$\alpha $$
α
and a logarithmic energy scale L—a reordering of terms as $$G(\alpha ,L) = 1 \pm \sum _{j \ge 0} \alpha ^j H_j(\alpha L)$$

G

(
α
,
L
)

=
1
±

∑

j
≥
0

α
j

H
j

(
α
L
)

is the corresponding log expansion. In a first part of this paper, we derive the leading log order $$H_0$$

H
0

and the next-to$$^{(j)}$$

(
j
)

-leading log orders $$H_j$$

H
j

from the Callan–Symanzik equation. In particular, $$H_j$$

H
j

only depends on the $$(j+1)$$

(
j
+
1
)

-loop $$\beta $$
β
-function and anomalous dimensions. In two specific examples, our formulas reproduce the known expressions for the next-to-next-to-leading log approximation in the literature: for the photon propagator Green’s function in quantum electrodynamics and in a toy model, where all Feynman graphs with vertex sub-divergences are neglected. In a second part of this work, we review the connection between the Callan–Symanzik equation and Dyson–Schwinger equations, i.e., fixed-point relations for the Green’s functions. Combining the arguments, our work provides a derivation of the log expansions for Green’s functions from the corresponding Dyson–Schwinger equations.
Cognition-Oriented Treatments for Older Adults: a Systematic Overview of Systematic Reviews
Authors: Gavelin Hanna Malmberg , Lampit Amit , Hallock Harry , Sabatés Julieta , Bahar-Fuchs Alex 
Published: April 2020

AbstractCognition-oriented treatments – commonly categorized as cognitive training, cognitive rehabilitation and cognitive stimulation – are promising approaches for the prevention of cognitive and functional decline in older adults. We conducted a systematic overview of meta-analyses investigating the efficacy of cognition-oriented treatments on cognitive and non-cognitive outcomes in older adults with or without cognitive impairment. Review quality was assessed by A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR). We identified 51 eligible reviews, 46 of which were included in the quantitative synthesis. The confidence ratings were “moderate” for 9 (20%), “low” for 13 (28%) and “critically low” for 24 (52%) of the 46 reviews. While most reviews provided pooled effect estimates for objective cognition, non-cognitive outcomes of potential relevance were more sparsely reported. The mean effect estimate on cognition was small for cognitive training in healthy older adults (mean Hedges’ g = 0.32, range 0.13–0.64, 19 reviews), mild cognitive impairment (mean Hedges’ g = 0.40, range 0.32–0.60, five reviews), and dementia (mean Hedges’ g = 0.38, range 0.09–1.16, seven reviews), and small for cognitive stimulation in dementia (mean Hedges’ g = 0.36, range 0.26–0.44, five reviews). Meta-regression revealed that higher AMSTAR score was associated with larger effect estimates for cognitive outcomes. The available evidence supports the efficacy of cognition-oriented treatments improving cognitive performance in older adults. The extent to which such effects are of clinical value remains unclear, due to the scarcity of high-quality evidence and heterogeneity in reported findings. An important avenue for future trials is to include relevant non-cognitive outcomes in a more consistent way and, for meta-analyses in the field, there is a need for better adherence to methodological standards. PROSPERO registration number: CRD42018084490.
Experimental Investigation on the Friction and Wear Characteristics of Palm Seed Powder Reinforced Brake Pad Friction Composites
Authors: Jeganmohan Sudhanraj , Sugozu Banu , Kumar Mukesh , Selvam David Raja 
Published: April 2020

AbstractIn this research work, palm seed power (0–9 wt%, step of 3%; four composites sample, namely P0, P3. P6, P9) were used to reinforce master batch of friction composite materials containing phenolic resin binder, steel swarf fibre, cashew, alumina, graphite, copper and zinc. The fabrications were as per standard industrial practice via hot compression moulding route. Thereafter, samples were cut and characterized for their tribological characteristics on specifically designed braking dynamometer using grey cast iron disc as per TS 555 and TS 9076 standards. Physical and mechanical properties such as hardness and density of the samples were also determined. Further, multi-criteria-decision-making like Preference Selection Index methods are used to ascertain ranking of material alternatives based on performance criteria. Both the subjective analysis and PSI output are in agreement with each other. Hence, such techniques often found suitable for decision-making or ranking of materials alternatives when performance criteria are of conflicting in nature.
Emission modelling of hydrodynamic AGN jet simulations
Authors: van der Westhuizen Izak P. , van Soelen Brian , Meintjes Petrus J. 
Published: April 2020

AbstractRadio-loud Active Galactic Nuclei (AGN) produce relativistic jets that can be modelled with relativistic hydrodynamic (RHD) simulations. In this study we present two such simulations of jets, used to investigate the parameters required to reproduce structures consistent with both FR I and FRII jets. In the first simulation a Lorentz factor of 10 and supersonic flow of Mach 30 were chosen, while for the second simulation a Lorentz factor of 1.0014 with a supersonic flow of Mach 4 was used. Over similar distances scales the first case shows a well collimated beam with a strong shock at the interface between the jet and ambient medium while the second case shows a less stable beam and a larger cocoon. To determine whether the simulated physical structures are consistent with the observed FR I/II jets, the synchrotron emission has been calculated to produce radio maps at a single frequency of 1.5 GHz.
Use of Imitation Training for Targeting Grammar: A Narrative Review
Authors: Eisenberg Sarita L. , Bredin-Oja Shelley L. , Crumrine Kasey 
Published: April 2020

Purpose
The purpose of this narrative review was to examine the evidence for imitation training for targeting grammar in children with developmental language disorder.

Method
Studies investigating imitation training were compiled from two databases—PsycINFO and Linguistics and Language Behavior Abstracts—as well as from reference lists of several books and articles reviewing language therapy.

Results
Twenty-one studies were reviewed. We summarized the demographic and methodological characteristics of the included studies. We identified substantial differences in the implementation of imitation training across the studies and noted a lack of studies considering how those differences might affect therapy outcome. Studies showed a rapid increase in the production of grammatical targets during imitation training activities, higher performance relative to a control group that did not receive any therapy, and generalization to untrained exemplars. However, the studies did not unequivocally link the increased performance to the imitation training therapy. Studies also showed limited generalization to conversational speech. Conversationally based therapy resulted in faster or higher usage in conversational speech, while imitation training resulted in faster immediate gains in usage during therapy trials.

Conclusion
We believe that imitation training can continue to be a useful tool in a speech-language pathologist's toolbox, but with suggested modifications. Specifically, we suggest use of imitation training as a means for rapidly achieving production of previously absent grammatical targets. However, we do not recommend sole or long-term use of imitation training for working on grammar. Further research is needed to refine our use of the procedure.