bluuebunny/crossref_metadata_2025 huggingface dataset:
Out‐colourings of digraphs
Authors: Alon Noga , Bang‐Jensen Jørgen , Bessy Stéphane
Published: July 2019

We study vertex colourings of digraphs so that no out‐neighbourhood is monochromatic and call such a colouring an out‐colouring. The problem of deciding whether a given digraph has an out‐colouring with only two colours (called a 2‐out‐colouring) is ‐complete. We show that for every choice of positive integers there exists a ‐strong bipartite tournament, which needs at least colours in every out‐colouring. Our main results are on tournaments and semicomplete digraphs. We prove that, except for the Paley tournament , every strong semicomplete digraph of minimum out‐degree at least three has a 2‐out‐colouring. Furthermore, we show that every semicomplete digraph on at least seven vertices has a 2‐out‐colouring if and only if it has a balanced such colouring, that is, the difference between the number of vertices that receive colour 1 and colour 2 is at most one. In the second half of the paper, we consider the generalization of 2‐out‐colourings to vertex partitions of a digraph so that each of the three digraphs induced by respectively, the vertices of , the vertices of and all arcs between and , have minimum out‐degree for a prescribed integer . Using probabilistic arguments, we prove that there exists an absolute positive constant so that every semicomplete digraph of minimum out‐degree at least has such a partition. This is tight up to the value of .
Efficacy of direct‐acting antivirals: UK real‐world data from a well‐characterised predominantly cirrhotic HCV cohort
Authors: Macken Lucia , Gelson William , Priest Matthew , Abouda George , Barclay Stephen , Fraser Andrew , Healy Brendan , Irving Will , Verma Sumita
Published: July 2019

Direct‐acting antivirals (DAAs) have revolutionised the management of chronic hepatitis C virus (HCV) infection. We describe UK real‐world DAA experience. Individuals commencing HCV treatment containing a DAA regimen (Mar 2014‐Nov 2016), participating in the National HCV Research UK (HCVRUK) Cohort Study were recruited from 33 UK HCV centers. The data were prospectively entered at sites onto a centralised database. The data were reported as median (Q1‐Q3). Of the 1448 treated patients, 1054 (73%) were males, the median age being 54 years (47‐60), 900 (62%) being genotype 1 and 455 (31%) genotype 3. The majority, 887 (61%) had cirrhosis, and 590 (41%) were treatment‐experienced. DAA regimens utilised: genotype1 sofosbuvir (SOF)/Ledipasvir/±Ribavirin (625/900, 69%) and Ombitasvir/Paritaprevir/Dasabuvir/±RBV (220/900, 24%), and in genotype 3 SOF/Daclatasvir + RBV (256/455, 56%) and SOF/pegylated interferon/RBV (157/455, 35%). Overall, 1321 (91%) achieved sustained virological response (SVR12), genotype 1 vs 3, 93% vs 87%, P < .001. Prior treatment, presence of cirrhosis and treatment regimen did not impact SVR12. Predictors of treatment failure were genotype 3 infection, OR, 2.015 (95% CI: 1.279‐3.176, P = .003), and male sex, OR, 1.878 (95% CI: 1.071‐3.291, P = .028). Of those with hepatic decompensation at baseline (n = 39), 51% (n = 20) recompensated post‐treatment, lower baseline serum creatinine being associated with recompensation (P = .029). There were two liver‐related deaths, both having decompensated disease. This real‐world UK data, comprising of a predominantly cirrhotic HCV genotype 1/3 cohort, confirms DAA efficacy with an overall 91% SVR12, with 51% recompensating post‐treatment. Genotype 3 infection was a predictor of treatment failure.
Impacts of climate change on characteristics of daily‐scale rainfall events based on nine selected GCMs under four CMIP5 RCP scenarios in Qu River basin, east China
Authors: Gao Chao , Booij Martijn J. , Xu Yue‐Ping
Published: July 2019

Climate change significantly influences characteristics of rainfall events including rainfall depth, rainfall duration, inter‐event time and temporal patterns that directly affect water resources management, flood defence and hydraulic structure design. In this study, a framework is proposed to analyse daily‐scale rainfall event characteristics based on global climate model (GCM) simulations. This framework includes bias correction of raw GCM‐simulated rainfall series, selection of good‐performing bias‐corrected GCMs based on the mean absolute percentage error (MAPE) and evaluation of selected GCMs' skills in simulating rainfall event characteristics and finally assessment of changes in rainfall event characteristics in the future. In this study, 17 GCMs, four representative concentration pathways (i.e., RCP2.6, RCP4.5, RCP6.0 and RCP8.5) and two future periods (i.e., 2041–2070 and 2071–2100) are considered. After bias correction of the GCMs using the monthly‐scale double gamma distribution, 9 out of 17 GCMs with MAPE values smaller than 20% in the historical period 1971–2000 are selected. In general, these selected GCMs well capture the rainfall characteristics of different rainfall event classes. The multi‐model ensembles suggest that compared to the historical period, the frequency of rainfall events with an extreme depth, short duration and long inter‐event time will increase in the two future periods and the change in 2071–2100 is generally larger than that in 2041–2070, indicating that more extreme climate conditions may occur in Qu River basin in the future. Moreover, the temporal patterns of heavy rainfall events will become more non‐uniform with more concentrated peak rainfall. The frequency of the delayed rainfall type (i.e., peaks occurring at the end of the rainfall event) will increase in the future, which can probably cause more severe floods and is very detrimental to flood defence in this study area.
Hydrolysis of chlorogenic acid in apple juice using a p‐coumaryl esterase of Rhizoctonia solani
Authors: Siebert Mareike , Berger Ralf Günter , Pfeiffer Franziska
Published: July 2019

BACKGROUND

Apple juice is rich in polyphenolic compounds, especially in chlorogenic acid. A sour and bitter taste has been attributed to the compound. Chlorogenic acid in coffee powder was quickly hydrolysed by a p‐coumaryl esterase of Rhizoctonia solani (RspCAE) at its optimal pH of 6.0. It was unknown, however, if RspCAE would also degrade chlorogenic acid under the strongly acidic conditions (pH 3.3) present in apple juice.

RESULTS

Treatment of apple juice with RspCAE led to a chlorogenic acid degradation from 53.38 ± 0.94 mg L−1 to 21.02 ± 1.47 mg L−1. Simultaneously, the caffeic acid content increased from 6.72 ± 0.69 mg L−1 to 19.33 ± 1.86 mg/L−1. The aroma profile of the enzymatically treated sample and a control sample differed in only one volatile. Vitispirane had a higher flavour dilution factor in the treated juice. Sensory analysis showed no significant difference in the taste profile ( p < 0.05).

CONCLUSION

These results demonstrated a high stability and substrate specificity of RspCAE. An increase in caffeic acid and a concurrent decrease in chlorogenic acid concentration may exert a beneficial effect on human health. © 2019 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Evaluating the metabolic perturbations in Mangifera indica (mango) ripened with various ripening agents/practices through gas chromatography ‐ mass spectrometry based metabolomics
Authors: Ganneru Sireesha , Shaik Hussain , Peddi Kiranmayi , Mudiam Mohana Krishna Reddy
Published: July 2019

Mangifera indica L. (mango) is said to be the king of fruits due to its rich nutritional properties and mainly originates from the Indian sub‐continent. The consumption pattern of the mangoes has increased drastically, due to which, many ripening practices/agents were used to make it ready‐to‐eat fruit or juice for the consumers. The fruit quality and metabolic composition are said to be altered due to different ripening agents/practices. The present communication mainly deals to understand the metabolic perturbations in mango fruits due to different ripening practices/agents (room temperature ripening, ethylene, and calcium carbide) using gas chromatography ‐ mass spectrometry based metabolomics. The partial least square‐discriminant analysis has found 16 differential metabolites for different ripening agents/practices which are belong to the classes of amino acids, fatty acids, sugars, and polyols. Four metabolic pathways were found to alter in the fruit metabolome due to different ripening agents/practices. Fructose, glucose, and galactose were found to be significantly up‐regulated due to calcium carbide ripening in comparison to other ripening agents/practices. Overall findings from the present study advocates that mass spectrometry based metabolomics can be valuable tool to understand the fruit quality and safety with respect to consumer health.
Is Ultrasound‐Guided Core Biopsy as Safe as Fine‐Needle Aspiration, and Does It Add Significantly to the Diagnosis of Suspected Peritoneal Malignancy?
Authors: Kipper Benjamin , McGahan John P. , Loehfelm Thomas W. , Fananapazir Ghaneh
Published: July 2019

Objectives

We undertook this retrospective review to compare the safety and diagnostic yield of core biopsy (CB) compared to fine‐needle aspiration (FNA) in patients with suspected peritoneal malignancy.

Methods

This retrospective study included 35 patients who underwent ultrasound (US)‐guided percutaneous biopsy of a peritoneal mass. Success rates of US‐guided biopsy of these masses using the CB technique, FNA, or the combination of the two were compared. Outcomes of tissue adequacy, the final pathologic diagnosis, and complications were recorded. The binary outcome variable was adequate tissue obtained.

Results

Adequate specimens were obtained in 94% (33 of 35) of the cases. There were 19 CBs, with 100% of samples sufficient for diagnosis (19 of 19). Thirty‐one FNAs were performed, of which 7 were insufficient, with a diagnostic yield of 77% (24 of 31). There was a statistically significant difference between FNA and CB in providing more adequate tissue for diagnosis in our population (P = .035). There were no significant complications in either group.

Conclusions

The use of the CB technique when performing US‐guided percutaneous biopsy of peritoneal masses provides better tissue for diagnosis compared to FNA. Additional benefits of CB, including genomic testing and tumor subtyping, make this technique a good addition to FNA, without significant complications.
Endoscope‐assisted transoral accessory parotid mass excision: Multicenter prospective observational study
Authors: Kim Jin Pyeong , Lee Dong Kun , Moon Jeong Hwan , Ryu Jun Sun , Woo Seung Hoon
Published: July 2019

Objective

Transoral surgery is gaining favor because it has the advantage of leaving no scar after surgery. The aim of this study was to evaluate the technical feasibility and safety of endoscope‐assisted transoral accessory parotid mass excision.

Study Design

Multicenter, prospective, observational study.

Methods

This study was designed as a 7‐year, prospective, multicenter evaluation of endoscope‐assisted transoral accessory parotid mass excision. Clinical outcomes and complications related to the procedures were evaluated in patients.

Results

Twenty patients underwent endoscope‐assisted transoral accessory parotid mass excisions, and 22 patients underwent conventional parotidectomy approach excisions. There was no significant difference with respect to overall demographic characteristics between the groups. However, the operation times were shorter in the transoral approach group (P = 0.001), and cosmetic satisfaction was much better in the transoral group (P < 0.001).

Conclusion

Endoscope‐assisted transoral accessory parotid mass excision is a potentially safe and effective procedure with excellent outcomes.

Level of Evidence

2

Laryngoscope, 130:1218–1226, 2020
Copolymerization of Pentafluorophenylmethacrylate with Hydrophilic Methacrylamide Monomers Induces Premature Hydrolytic Cleavage
Authors: Heraud Clemence , Basuki Johan , Hughes Timothy C. , Mueller Michael
Published: July 2019

Active ester polymers are commonly used for fast development of novel polymer libraries, but they require post‐polymerization modification, which is not atom‐efficient or economical. In order to more efficiently produce 2‐hydroxypropyl methacrylamide (HPMAm) libraries, it would be advantageous to perform a direct copolymerization with active ester monomers. In this work, the synthesis of copolymer libraries of pentafluorophenyl methacrylate (PFPMA) and the hydrophilic monomer HPMAm is investigated. Surprisingly, HPMAm induces premature hydrolytic cleavage of PFPMA, which occurs during polymerization and depends on the HPMAm/PFPMA feed ratio. Copolymerization of PFPMA with N‐isopropylmethacrylamide and the methacrylate monomers 2‐hydroxypropylmethacrylate and N‐isopropylmethacrylate reveals that the hydrolytic cleavage is promoted by copolymerization with methacrylamides only. By switching from a thermal‐ to a light‐based initiator and lowering the reaction temperature, premature hydrolytic cleavage of PFPMA is avoided and allows direct copolymerization of HPMAm together with PFPMA to create polymer libraries for biomaterial screening.
Novel GLI3 variant causes Greig cephalopolysyndactyly syndrome in three generations of a Lithuanian family
Authors: Siavrienė Evelina , Mikštienė Violeta , Radzevičius Darius , Maldžienė Živilė , Rančelis Tautvydas , Petraitytė Gunda , Tamulytė Giedrė , Kavaliauskienė Ingrida , Šarkinas Laurynas , Utkus Algirdas , Kučinskas Vaidutis , Preikšaitienė Eglė
Published: July 2019

Background

Preaxial polydactyly type IV, also referred as polysyndactyly, has been described in a few syndromes. We present three generations of a family with preaxial polydactyly type IV and other clinical features of Greig cephalopolysyndactyly syndrome (GCPS).

Methods and results

Sequencing analysis of the GLI3 coding region identified a novel donor splice site variant NC_000007.14(NM_000168.6):c.473+3A>T in the proband and the same pathogenic variant was subsequently identified in other affected family members. Functional analysis based on Sanger sequencing of the proband's complementary DNA (cDNA) sample revealed that the splice site variant c.473+3A>T disrupts the original donor splice site, thus leading to exon 4 skipping. Based on further in silico analysis, this pathogenic splice site variant consequently results in a truncated protein NP_000159.3:p.(His123Argfs*57), which lacks almost all functionally important domains. Therefore, functional cDNA analysis confirmed that the haploinsufficiency of the GLI3 is the cause of GCPS in the affected family members.

Conclusion

Despite the evidence provided, pathogenic variants in the GLI3 do not always definitely correlate with syndromic or nonsyndromic clinical phenotypes associated with this gene. For this reason, further transcriptomic and proteomic evaluation could be suggested.
Targeting PLIN2/PLIN5‐PPARγ: Sulforaphane Disturbs the Maturation of Lipid Droplets
Authors: Tian Sicong , Lei Peng , Teng Chunying , Sun Yao , Song Xinyue , Li Baolong , Shan Yujuan
Published: July 2019

Scope

The effects of sulforaphane (SFN) on the maturation of lipid droplets (LDs)—the storage units for free fatty acids and sterols as triacylglycerides (TAG) and cholesterol esters (CE)—are far from being understood, despite the fact that SFN is known to be beneficial for ameliorating lipid metabolism disorders.

Methods and Results

High‐fat‐intake models are established in both HHL‐5 hepatocytes and rodents. The numbers and sizes of LDs are decreased by SFN. The accumulation of lipid core components (TAG & CE) is reduced and the expression of their key synthetases, acyl‐coenzyme A: diacylglycerol acyltransferases 2 (DGAT2) and acyl‐coenzyme A: cholesterol acyltransferases 1 (ACAT1), is also inhibited. Moreover, SFN decreases LD‐associated protein PLIN2 and PLIN5 expression, but not that of PLIN1 and PLIN3, both in vivo and in vitro. Furthermore, over‐expression of peroxisome proliferator‐activated receptor gamma (PPARγ) induces the accumulation of TAG and the up‐regulation of PLIN2 and PLIN5, which are not reversed by SFN. These results suggest that PPARγ may be a target of SFN in lipid metabolism.

Conclusion

SFN disturbs LD maturation by inhibiting the formation of the neutral lipid core and decreases PLIN2 and PLIN5 via down‐regulation of PPARγ.
Nerve entrapments related to muscle herniation
Authors: Tong Olivia , Bieri Phyllis , Herskovitz Steven
Published: July 2019

Background

Muscle herniation is a muscle protrusion through a fascial defect. It is a rarely reported cause of nerve entrapment.

Methods

We present a case of superficial fibular (peroneal) neuropathy associated with a fibularis (peroneus) brevis muscle herniation and a review of the literature on nerve entrapments secondary to muscle herniation unrelated to compartment syndrome.

Results

Eleven cases of nerve entrapments secondary to muscle herniation were identified. The superficial fibular nerve (SFN) was the most commonly entrapped nerve by fibularis muscle herniation. Patients presented with pain, numbness, or paresthesias, and an often tender, small palpable mass with a Tinel sign. Muscle MRI or ultrasound identified the lesion, and patients responded well to fasciotomy.

Conclusions

The most commonly reported nerve entrapped by muscle herniation is the SFN secondary to fibularis muscle herniation. Characteristic clinical and imaging (MRI or ultrasound) features are diagnostic, and there is a salutary response to fasciotomy.
Physiological differences in sarcolemmal excitability between human muscles
Authors: Lee James H. F. , Boland‐Freitas Robert , Ng Karl
Published: July 2019

Introduction

The sarcolemmal resting membrane potential (RMP) affects muscle excitability, contractility, and force generation. However, there are limited In vivo data on the normal RMP of the human sarcolemma between muscles. We hypothesize that the in vivo RMP may differ between human muscles with different physiological roles.

Methods

Muscle velocity recovery cycles were recorded from a proximal antigravity muscle, the rectus femoris, and compared with paired recordings from a distal non‐antigravity muscle, the tibialis anterior, in 34 normal individuals.

Results

Significant differences in muscle relative refractory period (3.55 millseconds vs 3.87 milliseconds, P = .002), early supernormality (14.22% vs 10.50%, P < .0001), and late supernormality (5.43% vs 3.50%, P < .0001) were observed.

Discussion

The results strongly suggest a less negative RMP in tibialis anterior vs rectus femoris and attest to intermuscle differences in normal excitability and physiology. This novel finding employing an in vivo methodology highlights the need for muscle‐specific normative data in future studies.
Shifting Diets of Lake Trout in Northeastern Lake Michigan
Authors: Luo Miles K. , Madenjian Charles P. , Diana James S. , Kornis Matthew S. , Bronte Charles R.
Published: July 2019

Prey fish communities in Lake Michigan have been steadily changing, characterized by declines in both the quantity and quality of Alewife Alosa pseudoharengus. To evaluate concurrent changes in the diet of Lake Trout Salvelinus namaycush in northeastern Lake Michigan, we analyzed stomach contents of Lake Trout caught during gill-net surveys and fishing tournaments from May through October 2016. We then compared the composition, on a wet-weight basis, of 2016 diets with those previously described in a recent survey conducted in 2011. Overall, we found that Lake Trout diets in 2016 consisted mostly (94% by wet weight) of Alewives and Round Goby Neogobius melanostomus. Averaging across May through October, 61% of the Lake Trout diet consisted of Alewives. A clear seasonal shift was apparent: the diet was dominated by Round Goby (67%) during May–June, whereas Alewives dominated the diet (76%) during July–October. Seasonal dominance of Round Goby in spring Lake Trout diets has not been previously observed in northeastern Lake Michigan as Round Goby represented only 21% of the Lake Trout diet in spring of 2011. Diet composition of Lake Trout caught in gill nets did not significantly differ from diet composition of Lake Trout caught by anglers in either the May–June period or the July–October period. Although Lake Trout showed increased diet flexibility in 2016 compared with 2011, Alewives were still the predominant diet component during 2016, despite reduced Alewife biomass throughout Lake Michigan. Nonetheless, this further evidence of diet plasticity suggests that Lake Trout may be resilient to ongoing and future forage base changes.
Bacterial Stern layer diffusion: experimental determination with spectral induced polarization and sensitivity to nitrite toxicity
Authors: Mellage Adrian , Smeaton Christina M. , Furman Alex , Atekwana Estella A. , Rezanezhad Fereidoun , Van Cappellen Philippe
Published: July 2019

Spectral induced polarization signatures have been used as proxies for microbial abundance in subsurface environments, by taking advantage of the charged properties of microbial cell membranes. The method's applicability, however, remains qualitative, and signal interpretation ambiguous. The adoption of spectral induced polarization as a robust geo‐microbiological tool for monitoring microbial dynamics in porous media requires the development of quantitative relationships between biogeochemical targets and spectral induced polarization parameters, such as biomass density and imaginary conductivity (σ″). Furthermore, deriving cell density information from electrical signals in porous media necessitates a detailed understanding of the nature of the cell membrane surface charge dynamics. We present results from a fully saturated sand‐filled column reactor experiment where Shewanella oneidensis growth during nitrate reduction to ammonium was monitored using spectral induced polarization. While our results further confirm the direct dependence of σ″ on changing cell density, Cole–Cole derived relaxation times also record the changing surface charging properties of the cells, ascribed to toxic stress due to nitrite accumulation. Concurrent estimates of cell size yield the first measurement‐derived estimation of the apparent surface ion diffusion coefficient for cells (Ds = 5.4 ±1.3 µm2 s−1), strengthening the link between spectral induced polarization and electrochemical cell polarization. Our analysis provides a theoretical framework on which to build σ″–cell density relations using bench‐scale experiments, leading to eventual robust non‐destructive monitoring of in situ microbial growth dynamics.
Simultaneous separation and determination of hirsutine and hirsuteine by cyclodextrin‐modified micellar electrokinetic capillary chromatography
Authors: Wang Mengli , Guo Jing , Wang Zhiying , Zhang Guangbin , Yu Haixia , Chang Ruimiao , Chen Anjia
Published: July 2019

Introduction

Hirsutine and hirsuteine are the main pharmacological activity ingredients of Uncaria rhynchophylla (UR), playing an important role in treating mental and cardiovascular diseases, such as Alzheimerʼs disease, hypertension, Parkinson's disease, potential anti‐cancer activities and so on.

Objective

To develop a cyclodextrin‐modified micellar electrokinetic capillary chromatography (CD‐MEKC) method for the simultaneous separation and determination of hirsutine and hirsuteine from UR and its formulations.

Methodology

The optimal method was developed by investigating influences of significant factors on the separation, and this method was successfully applied for the determination of hirsutine and hirsuteine in UR and its formulations.

Results

The optimal background electrolyte (BGE) consisted of 40 mM sodium dihydrogen phosphate (pH 7.0), 150 mM 2,6‐dimethyl‐β‐cyclodextrin (DM‐β‐CD), 3 mM mono‐(6‐ethylenediamine‐6‐deoxy)‐β‐cyclodextrin (ED‐β‐CD), and 30 mM sodium cholate (SC). Under these conditions, hirsutine and hirsuteine were successfully separated within 13 min at the separation voltage of 15 kV, temperature of 25°C and the detection wavelength of 224 nm. For the analytes, linear calibration curves were performed within the range 5.0–160.0 μg/mL. The limit of detection (LOD, S/N = 3) and the limit of quantitation (LOQ, S/N = 10) were 0.41, 1.42 μg/mL for hirsutine and 0.60, 2.17 μg/mL for hirsuteine, respectively. The recoveries of three samples were from 97.9% to 102.3%.

Conclusion

The method was successfully applied to the determination of hirsutine and hirsuteine in UR and its formulations. Meanwhile, it provides an effective reference of the quality control of UR and its formulations.
Identifying pregnancies in insurance claims data: Methods and application to retinoid teratogenic surveillance
Authors: MacDonald Sarah C. , Cohen Jacqueline M. , Panchaud Alice , McElrath Thomas F. , Huybrechts Krista F. , Hernández‐Díaz Sonia
Published: July 2019

Purpose

The purpose of the study is to develop an algorithm to identify pregnancies in administrative databases and apply it to assess pregnancy rates and outcomes in women prescribed isotretinoin or tretinoin.

Methods

Using the 2011 to 2015 Truven Health MarketScan Database, we identified pregnancies, including losses and terminations. In a cohort design, nonpregnant women filling a prescription for isotretinoin or tretinoin were matched to five women without either prescription. Women were followed for 365 days or until conception, medication discontinuation, or enrollment discontinuation (“prescription episode”). Rates of pregnancy, risks of pregnancy losses, and prevalence of infant malformations at birth were assessed by exposure.

Results

We identified 2 179 192 livebirths, 8434 stillbirths, 2521 mixed births, 415 110 spontaneous abortions, 124 556 elective terminations, and 8974 unspecified abortions. There were 86 834 isotretinoin and 973 587 tretinoin episodes, matched to 5 302 105 unexposed women. Pregnancy rates were 3 (isotretinoin), 19 (tretinoin), and 34 (unexposed) per 1000 person‐years. Risk of spontaneous pregnancy losses were similar; however, terminations were more common in the isotretinoin‐exposed (28% [95% CI: 21%‐36%]) than the tretinoin‐exposed (10% [95% CI: 9%‐11%]) or unexposed pregnancies (6%). Malformations occurred in 4.5% (95% CI: 3.5%‐5.6%) of the tretinoin‐exposed pregnancies and 4.2% of the unexposed pregnancies (adjusted odds ratio: 1.16 [95% CI: 0.85‐1.58]); isotretinoin‐exposed births were too few to assess malformations.

Conclusions

Administrative databases can complement risk evaluation and mitigation strategies (REMS) for known teratogens and contribute to safety surveillance for other medications. Here, isotretinoin‐exposed pregnancy rates were low, but existent, and many pregnancies were terminated. Tretinoin exposure was not associated with a meaningfully elevated risk of losses or malformations as compared with unexposed pregnancies.
A plan to diversify a transgenic blight‐tolerant American chestnut population using citizen science
Authors: Westbrook Jared W. , Holliday Jason A. , Newhouse Andrew E. , Powell William A.
Published: July 2019

Societal Impact Statement

Over four billion American chestnut trees have been killed as a result of an introduced pathogen, the chestnut blight fungus. Recently, transgenic blight‐tolerant American chestnut trees have been produced by inserting a gene from wheat into the American chestnut genome. Pending federal approval to use these transgenic trees for large‐scale forest restoration, this would be the first instance where a transgenic approach has been used to restore a tree species that has been rendered functionally extinct by an introduced pathogen. With the help of citizen scientists, we estimate that large‐scale forest restoration using blight‐tolerant American chestnut trees is possible within the next few decades.

Summary

Breeding transgenic blight‐tolerant American chestnuts with susceptible wild‐type (WT) trees is potentially an efficient method to rescue the genetic diversity and adaptive capacity of the American chestnut population for large‐scale restoration.

To develop a breeding plan to diversify a transgenic blight‐tolerant population, we simulated pedigrees to estimate inbreeding coefficients and effective population size in scenarios involving outcrossing 1–4 transgenic founders to a maximum of 1,500 WT trees over 1–5 generations. We also simulated marker‐assisted introgression scenarios to minimize the extent of the transgenic founder genome, especially on the transgene carrier chromosome.

Simulations suggest that the effective population size may be increased to >500, and the average inbreeding coefficient reduced to <0.01, by outcrossing a single transgenic founder over five generations to 2, 25, 50, 150, and 450 (677 total) WT parents. Three generations of marker‐assisted introgression is predicted to decrease the length of the founder genome to between 7% and 13% of the transgene carrier chromosome length as compared to 42% with event selection (ES) only. Transgenic outcross selections may be intercrossed to select progeny homozygous for the transgene for planting in seed orchards.

A diversified population of transgenic blight‐tolerant American chestnut is estimated to be available for use in large‐scale forest restoration 20–35 years after federal approval to distribute the trees. In contrast, trees from earlier generations would be available almost immediately after federal approval for personal or horticultural plantings. Methods to accelerate pollen production and outcrossing are discussed.
Design of a basigin‐mimicking inhibitor targeting the malaria invasion protein RH5
Authors: Warszawski Shira , Dekel Elya , Campeotto Ivan , Marshall Jennifer M. , Wright Katherine E. , Lyth Oliver , Knop Orli , Regev‐Rudzki Neta , Higgins Matthew K. , Draper Simon J. , Baum Jake , Fleishman Sarel J.
Published: July 2019

Many human pathogens use host cell‐surface receptors to attach and invade cells. Often, the host‐pathogen interaction affinity is low, presenting opportunities to block invasion using a soluble, high‐affinity mimic of the host protein. The Plasmodium falciparum reticulocyte‐binding protein homolog 5 (RH5) provides an exciting candidate for mimicry: it is highly conserved and its moderate affinity binding to the human receptor basigin (KD ≥1 μM) is an essential step in erythrocyte invasion by this malaria parasite. We used deep mutational scanning of a soluble fragment of human basigin to systematically characterize point mutations that enhance basigin affinity for RH5 and then used Rosetta to design a variant within the sequence space of affinity‐enhancing mutations. The resulting seven‐mutation design exhibited 1900‐fold higher affinity (KD approximately 1 nM) for RH5 with a very slow binding off rate (0.23 h−1) and reduced the effective Plasmodium growth‐inhibitory concentration by at least 10‐fold compared to human basigin. The design provides a favorable starting point for engineering on‐rate improvements that are likely to be essential to reach therapeutically effective growth inhibition.
Improving the Stability of Organic–Inorganic Hybrid Perovskite Light‐Emitting Diodes Using Doped Electron Transport Materials
Authors: Kim Taejun , Kim Jin-Hoon , Triambulo Ross E. , Han Hyowon , Park Cheolmin , Park Jin-Woo
Published: July 2019

Herein, organic–inorganic hybrid perovskite light‐emitting diodes (PeLEDs) are fabricated under ambient air and all‐solution conditions. A novel N2 gas blowing step is applied during spin‐coating of the precursor solution to obtain uniform methylammonium lead bromide (MAPbBr3) perovskite nanocrystal films with fewer surface and interfacial defects than solution‐processed perovskite films. Furthermore, polyethylenimine (PEI) and poly[9,9‐dioctyl‐9′,9′‐bis[3‐(trimethylammonio)propyl][2,2′‐bi‐9H‐fluorene]‐7,7′‐diyl] (PFN) are used as doping agents in the widely used electron transport layer (ETL) material, 2,2′,2″‐(1,3,5‐benzinetriyl)‐tris(1‐phenyl‐1‐H‐benzimidazole) (TPBi), and act as passivation agents between the rough surface of the perovskite film and the ETL. Consequently, the high surface work function of PEI‐ and PFN‐doped TPBi results in reduced and balanced injection of electrons in the perovskite light‐emission layer (EML) of the PeLEDs, producing a maximum luminance (L) up to 14 358 and 11 465 cd m−2 for the PEI‐ and PFN‐based PeLEDs, respectively. The doped‐ETL‐based PeLEDs also show a 3.6 times longer L50 (i.e., the time needed for a 50% reduction in the initial value of L operated at 4 V) than the pure TPBi‐based PeLEDs, which need a separate poly(methyl methacrylate) (PMMA) film to act as the passivation layer between the EML and ETL.
Improved Alkali Intercalation of Carbonaceous Materials in Ammonia Solution
Authors: Márkus Bence Gábor , Szirmai Péter , Kollarics Sándor , Náfrádi Bálint , Forró László , Chacón-Torres Julio C. , Pichler Thomas , Simon Ferenc
Published: July 2019

Alkali‐intercalated graphite compounds represent a compelling modification of carbon with significant application potential and various fundamentally important phases. The intercalation of graphite with alkali atoms (Li and K) using liquid ammonia solution as a mediating agent is reported. Alkali atoms dissolve well in liquid ammonia, which simplifies and speeds up the intercalation process, and it also avoids the high temperature formation of alkali carbides. Optical microscopy, Raman, and electron spin‐resonance spectroscopy attest that the prepared samples are highly and homogeneously intercalated to a level approaching stage‐I intercalation compounds. The method and the synthesis route may serve as a starting point for the various forms of alkali‐atom‐intercalated carbon compounds (including carbon nanotubes and graphene), which can be exploited in energy storage and further chemical modifications.
National culture diversity in new venture boards: The role of founders' relational demography
Authors: Balachandran Chanchal , Wennberg Karl , Uman Timur
Published: July 2019

Research Summary

This study explains the conditions under which new venture boards are less or more culturally diverse in terms of their directors' country of birth. Longitudinal data on 5,515 Swedish ventures suggest that most directors are recruited from founders' proximate social settings—neighborhoods in which they reside and past workplaces—and that diversity levels in these social settings strongly predict the national culture diversity in venture boards. Given the rapid internationalization of workplaces and regions around the world, this paper provides important clues regarding how culturally diverse upper echelons are being incorporated into the organizational design of new ventures.

Managerial Summary

Most New Venture Boards exhibit limited diversity in terms of their directors' country of birth, as they are drawn from the venture founders' network. Yet, some new venture boards are indeed born diverse. Our study reveals that founders with prior exposure to culturally diverse workplaces and residential neighborhoods are much more likely to design a culturally diverse board at founding. Given the rapid internationalization of workplaces and regions in most countries around the world, our paper provides important clues regarding how national culture diversity in top management emerges and is being incorporated into the organizational design of new ventures.
Impact of model misspecification in shared frailty survival models
Authors: Gasparini Alessandro , Clements Mark S. , Abrams Keith R. , Crowther Michael J.
Published: July 2019

Survival models incorporating random effects to account for unmeasured heterogeneity are being increasingly used in biostatistical and applied research. Specifically, unmeasured covariates whose lack of inclusion in the model would lead to biased, inefficient results are commonly modeled by including a subject‐specific (or cluster‐specific) frailty term that follows a given distribution (eg, gamma or lognormal). Despite that, in the context of parametric frailty models, little is known about the impact of misspecifying the baseline hazard or the frailty distribution or both. Therefore, our aim is to quantify the impact of such misspecification in a wide variety of clinically plausible scenarios via Monte Carlo simulation, using open‐source software readily available to applied researchers. We generate clustered survival data assuming various baseline hazard functions, including mixture distributions with turning points, and assess the impact of sample size, variance of the frailty, baseline hazard function, and frailty distribution. Models compared include standard parametric distributions and more flexible spline‐based approaches; we also included semiparametric Cox models. The resulting bias can be clinically relevant. In conclusion, we highlight the importance of fitting models that are flexible enough and the importance of assessing model fit. We illustrate our conclusions with two applications using data on diabetic retinopathy and bladder cancer. Our results show the importance of assessing model fit with respect to the baseline hazard function and the distribution of the frailty: misspecifying the former leads to biased relative and absolute risk estimates, whereas misspecifying the latter affects absolute risk estimates and measures of heterogeneity.
Antichagasic profile of a Series of Mannich Base‐Type Derivatives: Design, Synthesis, in vitro Evaluation, and Computational Studies Involving Iron Superoxide Dismutase
Authors: Paucar Rocío , Martín‐Escolano Rubén , Moreno‐Viguri Elsa , Cirauqui Nuria , Marín Clotilde , Sánchez‐Moreno Manuel , Pérez‐Silanes Silvia
Published: July 2019

Chagas disease is a silent disease that continues to endanger millions of people and, due to its insufficient current chemotherapy, urgently requires the development of more effective drugs. With this objective, twenty‐six Mannich base derivatives were synthesized, and their in vitro activity was evaluated against Trypanosoma cruzi. Three out of the twenty‐six compounds showed interesting results, including IC50 values<10 μM and a selectivity index >20 in amastigote forms of Arequipa and SN3 T. cruzi strains. In addition, these compounds showed similar infection rates in Vero cells compared to those of benznidazole at 50 μM. Finally, some studies were performed to investigate the possible mechanism of action; moreover, computational studies proposed a binding mode of these derivatives to Fe‐SOD. This new series of compounds has an encouraging antichagasic profile with a simplified structure and synthetic routes. Therefore, the most active compounds should be considered as leads for further optimization of the antichagasic activity.
Machine learning approaches to facial and text analysis: Discovering CEO oral communication styles
Authors: Choudhury Prithwiraj , Wang Dan , Carlson Natalie A. , Khanna Tarun
Published: July 2019

Research Summary

We demonstrate how a novel synthesis of three methods—(a) unsupervised topic modeling of text data to generate new measures of textual variance, (b) sentiment analysis of text data, and (c) supervised ML coding of facial images with a cutting‐edge convolutional neural network algorithm—can shed light on questions related to CEO oral communication. With videos and corresponding transcripts of interviews with emerging market CEOs, we use this synthesis of methods to discover five distinct communication styles that incorporate both verbal and nonverbal aspects of communication. Our data comprises interviews that represent unedited expressions and content, making them especially suitable as data sources for the measurement of an individual's communication style. We then perform a proof‐of‐concept analysis, correlating CEO communication styles to M&A outcomes, highlighting the value of combining text and videographic data to define styles. We also discuss the benefits of using our methods versus current research methods.

Managerial Summary

CEOs spend most of their time communicating to investors, customers, and partners with the aim of influencing these various stakeholders. To what extent though does their effectiveness as leaders depend on a mixture of what they say and how they say it? We use cutting‐edge machine learning approaches to measure a CEO's communication style, which can give clues about the major strategic decisions a CEO's firm must make. With a collection of video interviews with 61 organizational leaders from emerging markets, we use textual analysis and facial image expression recognition to code whether CEOs are “excitable,” “stern,” “dramatic,” “rambling,” and “melancholy” in their communication styles. As a proof‐of‐concept, we also show that CEOs who were more dramatic in expressing themselves were also less likely to oversee major acquisitions. Therefore, not only can CEO communication styles help predict a firm's ability to grow, adapt to change, and reallocate existing assets, styles can also be coded more intuitively by using our new method, representing a vast improvement over previous methods in both accessibility and interpretability.
The bivalved arthropod Tuzoia from the Balang Formation (Cambrian Stage 4) of Guizhou, China, and new observations on comparative species
Authors: Wen Rongqin , Babcock Loren E. , Peng Jin , Liu Shuai , Liang Boyan
Published: July 2019

Tuzoia is a large, bivalved Cambrian arthropod having a widespread distribution in shallow‐shelf to deeper marine Lagerstätten; stratigraphically it ranges from Cambrian Series 2 through the Miaolingian Series. In the present study, three species are recognized from relatively deep‐water deposits of the Balang Formation (Cambrian Stage 4) of Guizhou, South China: Tuzoia sinensis Pan, 1957, T. bispinosa Yuan et Zhao, 1999 and T. lazizhaiensis sp. nov. The new species is unique in having 6–10 small marginal spines on the dorsal margin, an inflated anterior margin with three short, closely spaced marginal spines. These remains, which usually occur as disarticulated valves, are inferred to be parautochthonous. One new specimen of T. lazizhaiensis shows a stalked eye and antenna. New Tuzoia material from the Kaili Biota (Cambrian: Wuliuan Stage) of Guizhou, and from the Guanshan Biota (Cambrian Stage 4) of Yunnan, China, provide additional comparative information about the genus. Some new specimens of T. bispinosa from the Kaili Biota provide information on valve morphology and palaeoecology. One specimen of T. sinensis from the Guanshan Biota provides information on the appendages, and one specimen of T. tylodesa, from the Guanshan Biota adds provides information on the trunk and appendages.
Thinking (in) complexity: (In) definitions and (mis)conceptions
Authors: Teixeira de Melo Ana , Caves Leo Simon Dominic , Dewitt Anna , Clutton Evie , Macpherson Rory , Garnett Philip
Published: July 2019

The rise of complexity sciences has led to the development of new language about systems. Concepts such as ‘complex systems thinking'; or ‘complexity thinking'; have appeared in the literature, appealing to ways of thinking (in) complexity. The notion of ‘complex thinking,'; may be considered as referring to a mode of thinking more congruent with the complexity of the world. The widespread and sometimes undifferentiated usage of these concepts results in a lack of clarity and terminological confusion, which jeopardizes their heuristic and pragmatic value. We identify literature using terms related to thinking (in) complexity and use a combination of computational and qualitative methods to extract definitions and analyse their usage. We map the relationships of the concepts and their usage across different intellectual communities. Our goal is to clarify these concepts and to strengthen their pragmatic value for the promotion and management of positive changes in complex systems.
Fat‐Replacer Properties of Oxidized Cassava Starch Using Hydrogen Peroxide/Sodium Bicarbonate Redox System in Mayonnaise Formulation and Its Stability
Authors: León Orietta , Soto Diana , López Daniel , Muñoz‐Bonilla Alexandra , Fernández‐García Marta
Published: July 2019

The stability and fat‐replacer properties of mayonnaise prepared with oxidized sweet cassava starch is studied. In a first step, the oxidation of starch using different conditions, i.e., thermal and thermochemical processes with the redox pair system (H2O2/NaHCO3), is analyzed. Oxidized starches can be used to produce food grade emulsions without the addition of surfactant, then, the mayonnaise emulsions are prepared using oxidized starch paste as partial substituent of the fat. They show greater stability with respect to the mayonnaise prepared with the native paste due to electro‐steric effects and Pickering type that the oxidized starch exerts on the emulsion. The rheological performance of mayonnaises with oxidized starches is analyzed and compared with that of full‐fat mayonnaise; demonstrating the oxidized starches applicability as stabilizers and fat‐reducers. Finally, a sensory analysis of the mayonnaise emulsions is carried out where all mayonnaise samples are judged to be sensorially acceptable.
Improving the constant‐volume degree of combustion considering generatable range at low speed in a free‐piston engine linear generator system
Authors: Sato Mitsuhide , Naganuma Kaname , Nirei Masami , Yamanaka Yuichiro , Suzuki Tatsuki , Goto Takumi , Bu Yinggang , Mizuno Tsutomu
Published: July 2019

Series hybrid vehicles using free‐piston engine coupled with linear generator are expected for high‐efficiency energy conversion systems. Such engines do not have a crank mechanism, which greatly reduces the friction loss. In addition, the piston action can be controlled freely by the generation braking thrust by using an inverter control. In a conventional crank engine, past research has shown that delaying the piston motion after the combustion increases the maximum combustion pressure, and this delay brings a constant‐volume degree close to the Otto cycle. In the free‐piston system, a high braking thrust is needed at a low piston speed immediately after combustion. However, the highest braking thrust was limited in the low‐speed range because the back electromotive force of a permanent magnet synchronous generator was too small. This article shows the range that can be theoretically attained for a low‐speed generator. The delaying piston movement with only the braking thrust improved the effective work by 25% near the top dead center. © 2019 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.