bluuebunny/crossref_metadata_2025 huggingface dataset:
When is Muscle Sympathetic Nerve Activity ‘Abnormal’?
Authors: Badrov Mark B. , Keir Daniel A. , Tomlinson George , Notarius Catherine F. , Kimmerly Derek S. , Millar Philip J. , Shoemaker J Kevin , Floras John S.
Published: April 2020

The sympathetic nervous system participates in both short‐ and long‐term cardiovascular regulation. The microneurographic technique, enabling in humans direct recordings from the populations of post‐ganglionic sympathetic neurons innervating the skeletal muscle vasculature (i.e. muscle sympathetic nerve activity; MSNA), has yielded key insights into mechanisms of sympathetic regulation of the circulation in health, and, importantly, its contributions to cardiovascular disease development and progression. Due to its invasive nature, as well as the technical challenges involved in site acquisition and burst quantification, its application has been limited primarily to trained investigators studying small, selected cohorts, rather than populations. In healthy individuals, MSNA burst frequency or burst incidence, as measured under supine resting conditions, exhibit considerable inter‐individual variability, yet are highly reproducible within individuals over time. However, such variability, as well as the limited data, has impaired the establishment of age‐ and sex‐dependent normative values. Therefore, we aimed to develop resting MSNA reference charts, representing MSNA percentile curves, in a large cohort of young and older men and women. Specifically, we retrospectively assembled a dataset of 654 healthy, unmedicated normotensive (<140/90 mmHg) individuals from four participating Canadian laboratories, including 396 men (aged 18–71 yrs) and 258 women (aged 18–81 yrs), in whom baseline resting MSNA was evaluated over a minimum of 5 min. Quantile regression was used to estimate the 5th, 20th, 50th (i.e. median), 80th, and 95th percentiles for resting MSNA burst frequency and burst incidence in men and women as a function of age. Quantiles were parameterized as functions of age by both a one‐ and two‐term fractional polynomial model with power selected from a ladder of values (i.e. −2, −1, −0.5, 0.5, 1, 2, 3). Next, an iterative fitting approach was applied to the MSNA versus age data to determine the fractional coefficients and the combination of values for the two powers from the ladder that provided the greatest goodness of fit (i.e. lowest χ2). The 5th, 20th, 50th, 80th, and 95th percentiles for MSNA burst frequency and burst incidence in men and women as a function of age are displayed in the figure
below. In conclusion, these MSNA percentile curves, developed from a large sample of men and women, provide age‐ and sex‐related reference values for resting MSNA levels in healthy, normotensive individuals, and, furthermore, by establishing 95% confidence limits, may help inform comparative studies of disease states referenced to age‐ and sex‐matched controls.

Figure 1
Histone Deacetylase Inhibitors Enhance CRISPR‐Cas9 Cutting Efficiency
Authors: Bjornson Ymer M. , Huang Cody Y. , Castaneda Guadalupe , Yamomoto Emiko
Published: April 2020

The CRISPR/Cas9 technology is a prominent genome‐editing tool as an adaptable nuclease capable of producing a double strand break at almost any genomic loci. However, the modification of hematopoietic stem and progenitor cells (HSPC) via the homology directed repair (HDR) pathway is still inefficient. We hypothesize that histone deacetylase inhibitors (HDACi), such as Valproic Acid (VPA) and Sodium Butyrate (NaB), could enhance HDR efficiency by increasing the accessibility of the genome‐editing machinery. To address the potential utilization of HDACi therapeutically, we began by assessing the effect of VPA and NaB on cell growth and viability. No statistically significant effect on cell growth or viability was observed at concentrations as high as 50mM in a myeloid‐erythroid leukemic cell line (K562 cells). However, K562 cells only represent one lineage of the HSPC progeny. Therefore, we also treated an immortalized T lymphocyte cell line (Jurkat cells), representative of the lymphoid lineage, with either VPA or NaB. No effect on the growth pattern or viability of Jurkat cells was evident at concentrations as high as 5mM VPA and NaB. However, Jurkat cells did appear to be more susceptible to HDACi. Therefore, we ascertained that concentrations of HDACi lower than 5mM would be tolerated in HSPCs. At concentrations as low as 0.0005mM HDACi an enhancement in CRISPR cutting efficiency was evidenced as assessed in both K562 cells and Jurkat cells. This enhancement did not appear to be locus specific, in that two sets of CRISPR guide RNAs were analyzed revealing similar trends of enhancement. If the same trend follows, treatment with HDACi can be expanded to virtually any genome editing experiment utilizing the CRISPR‐Cas9 system to enhance cutting and thus therapeutic gene editing.

Support or Funding Information

CSUPERB

Effect of Valproic Acid and Butyrate on the Growth Curve of Hematopoietic Cell Lines A) Schematic representation of the experimental design utilized to test the effect of HDACi on the division of two hematopoietic cell lines. B) K562 cells treated with 300mM and 100mM VPA were not observed to divide. C) K562 cells treated with 500mM NaB were not observed to divide. D) Jurkat cells appear to be more susceptible to VPA. E) Jurkat cells treated with 50mM NaB proliferated at a much slower rate.

Figure 1
Elucidate Glycosyltransferase Specificities And Interactions for Rational Glycoengineering
Authors: Liang Chenguang , Chiang Austin W.T. , Hansen Anders H. , Arnsdorf Johnny , Schoffelen Sanne , Sorrentino James T. , Kellman Benjamin P. , Bao Bokan , Voldborg Bjørn G. , Lewis Nathan E.
Published: April 2020

The emergent market of new therapeutic glycoprofiles demands cost‐and‐labor efficient N‐linked glycoengineering, such as rational glycoengineering. However, rational glycoengineering remains challenging due to our limited understanding of the complex glycosyltransferase (GT) interactions. Predicting glycosylation outcomes of GT knockins/knockouts requires comprehensive and context‐specific knowledge of GT activities. To combat this issue, we proposed an improved low‐parameter Markov chain model to learn GT activities and used the learnt information to predict glycoprofiles impacted by complex glycoengineering. Specifically, we have quantified the impact of GT isozyme specificities and interactions by fitting the model with a compilation of single‐GT‐knockout erythropoietin (EPO) glycoprofiles for CHO cells. We then showed that the quantified GT impact can be generalized by our model framework to predict complex multiple‐GT‐knockout glycoprofiles of four diverse therapeutic drugs, including EPO, Rituximab, Enbrel, and alpha‐1 antitrypsin. Therefore, the proposed methodology allowed us to systematically unravel the complicated GT interactions beyond simple enzyme rules and with little a priori information. Such approach will further promote progress in rational glycoengineering by broadening our scope on the genetic basis of glycosylation, expediting product development for biopharmaceutical research.

Support or Funding Information

This work was conducted with support from the Novo Nordisk Foundation provided to the Center for Biosustainability at the Technical University of Denmark (NNF10CC1016517: A.L., A.W.T.C., A.H.H., B.G.V.) and NIGMS (R35 GM119850: N.E.L.)

Figure 1
A Universal CAR‐NK Cell Targeting Various Epitopes of HIV‐1 gp160
Authors: Lim Rebecca Marie , Rong Liang , Xie Jianming
Published: April 2020

Just like cancer cells that express cell‐surface tumor antigens, HIV‐infected cells express the envelope glycoprotein gp160 upon viral budding. Hence, engineering T cells and natural killer (NK) cells with anti‐gp160 chimeric antigen receptors (CAR) has emerged as a promising strategy to eradicate HIV‐infected cells. However, current CARs are limited by targeting a single epitope on gp160, which cannot counter the enormous HIV diversity. Here, we report the development of a universal CAR‐NK cell, which recognizes 2,4‐dinitrophenyl (DNP). This anti‐DNP CAR‐NK cell can be redirected to target various epitopes of the HIV envelope using DNP‐conjugated anti‐gp160 antibodies as adaptor molecules. We have shown that this CAR‐NK cell can recognize and kill mimic HIV‐infected cell lines expressing HIV‐1 subtypes B and C gp160. We additionally found that anti‐gp160 antibodies targeting membrane‐distal epitopes were more likely to activate universal CAR‐NK cells compared with those targeting membrane‐proximal epitopes. Moreover, we demonstrated that the universal CAR‐NK cells exhibited similar efficacy to the conventional CAR‐NK cells in targeting gp160‐expressing cells. Given that numerous anti‐gp160 antibodies are readily available, this universal CAR‐NK cell can potentially be used to overcome HIV diversity and to eradicate HIV‐infected cells.

Support or Funding Information

This study is supported by a startup fund from University of Southern California School of Pharmacy (J.X.) and a Pre‐Doctoral Fellowship in Pharmaceutical Sciences from the American Foundation for Pharmaceutical Education (R.M.L.).

Our proof‐of‐concept study demonstrates that we can direct universal CAR‐NK cells with DNP‐labeled broadly neutralizing antibodies to target and kill multiple variants of HIV‐infected cells. This strategy can help overcome HIV‐1 diversity and enhance eradication of infected cells, which is essential to finding an ultimate universal cure to HIV.

Figure 1
MicroRNA‐93, a Novel Potential Non‐Invasive Biomarker for Polycystic Ovary Syndrome (PCOS) Diagnosis
Authors: Chen Elizabeth , Wu Hsioa Li , Chen Yen Hao
Published: April 2020

PCOS is one of the most common endocrine disorders and affects at least 7–9% of reproductive‐aged women. However, PCOS diagnosis is a challenge for physicians because of the constellation of symptoms. From our previous studies, we found that the expression of microRNA‐93 (miR‐93) was up‐regulated in adipose tissue and related to the high incident of insulin resistance in PCOS women. As a result, we generated an adipose‐selective miR‐93 overexpression mouse (miR‐93AT+ mice) model which shows a PCOS‐like phenotype by using Cre/loxP DNA recombination. The level of miR‐93 expression in tissues was investigated by the q‐PCR method. The expression of miR‐93 was specifically increased in adipose tissue but not in muscle, liver, heart, or kidney tissues in miR‐93AT+ mice. However, the level of miR‐93 was overexpressed in the blood of the miR‐93AT+ mice, similar to results found in PCOS women. In addition, the level of miR‐93 was overexpressed (2.5 fold) in the feces of miR‐93AT+ mice. These data suggest that fecal miR‐93 may be applied as a potential novel non‐invasive biomarker for the diagnosis of PCOS. Additional studies of miR‐93 expression in feces from PCOS women are required to confirm this hypothesis.

Figure 1
Elucidation of the role of a lysine demyristoylase in adipose tissue‐myocardium crosstalk in cardiometabolic disease
Authors: Bagchi Rushita A. , Hu Tianjing , Major Jennifer L. , Cao Ji , Cavasin Maria A. , Mestroni Luisa , Lam Maggie P.Y. , Lin Hening , McKinsey Timothy A.
Published: April 2020

Histone deacetylase 11 (HDAC11) is the lone class IV HDAC whose biological function is largely unexplored. Previously, we demonstrated that deletion of HDAC11 in vivo stimulates brown adipose tissue (BAT) formation and beiging of white adipose tissue (WAT) via a genomic mechanism dependent on physical association with BRD2, a bromodomain and extraterminal (BET) acetyl‐histone binding protein in brown adipocytes. Here, we hypothesize that HDAC11 inactivation primes the heart for protection from pathological remodeling consequent to diet‐induced obesity (DIO) via modulation of adipose tissue transcriptome and secretome (Figure
). Gene expression analysis showed that selective pharmacologic inhibition of HDAC11 promotes brown adipocyte formation and Ucp1 expression in vitro and in vivo. HDAC11‐deficient mice, in response to high‐fat feeding, exhibit attenuated obesity, insulin resistance, and hepatic steatosis, concomitant with increased levels of the circulating cardioprotective hormone adiponectin. Using histological analysis, atomic force microscopy and quantitative mass spectrometry, we demonstrate that adipose tissue lacking HDAC11 is protected from pathologic remodeling as a consequence of chronic high caloric diet administration. At the level of the heart, we demonstrate for the very first time that HDAC11 functions as a negative regulator of physiological hypertrophy. HDAC11‐deficient hearts exhibit attenuated hypertrophic gene expression after chronic high‐fat feeding. HDAC11 loss also protects cardiomyocytes from pathological hypertrophy and fetal gene activation induced by high fat serum. Using orthogonal click chemistry, fluorescence correlation spectroscopy and super‐resolution microscopy, we establish for the first time that HDAC11 exerts its non‐genomic action by modifying fatty acylation of a cytosolic scaffolding protein, AKAP12 (a.k.a. gravin) and regulation of β‐adrenergic receptor signaling (Figure
). These findings outline a novel and highly druggable pathway for the regulation of cardiometabolic disease at the level of adipose tissue and the heart, and suggest a potential for HDAC11‐selective inhibitors for the treatment of obesity and cardiometabolic disease.

Support or Funding Information

This work was supported by NIH (HL116848, HL127240, HL147558, DK119594) and the American Heart Association (16SFRN31400013) to T.A.M. R.A.B. (FRN‐216927) and J.L.M. (FRN‐395620) received funding from the Canadian Institutes of Health Research.

Proposed model for HDAC11‐mediated cross‐talk between adipose tissue and the heart in cardiometabolic disease.

Figure 1

Schematic of the mechanism for HDAC11 modulation of AKAP12‐mediated βAR signaling.

Figure 2
Identifying CoADR and Npsr Function: A Metagenomic Analysis of The Sulfur Reducing Capabilities of CoADR and Npsr
Authors: Wragan Max , Crane E.J. , Cavalcanti Andre , Spindler Archie
Published: April 2020

Coenzyme‐A disulfide reductase (CoADR) and NADH‐dependent persulfide reductase (Npsr) are enzymes that have long been suspected to metabolize inorganic sulfur compounds due to their anaerobic environments in which they are found. Previous studies have had difficulty proving that CoADR and Npsr perform sulfur respiration through direct approach, which is why this research explored CoADR and Npsr’s relationship with sulfur reduction indirectly through metagenomic analysis. These results compiled the geochemistry, biochemistry, and microbiology of a wide variety of proteins with known functions and explored their relationship with CoADR and Npsr. Our data was compiled through the Joint Genome Institute’s metagenome database and run utilizing their BLAST program. This data was analyzed through Principle Component Analysis (PCA) which suggested CoADR and Npsr’s role as sulfur reducing enzymes via their correlation and alignment with other known sulfur reducing proteins, and their lack of their of with sulfate reducing, oxidative stress, and reversible sulfur cycling proteins.

Support or Funding Information

Funding for research came from NSF grant to Dr. EJ Crane. Research was conducted at the Department of Molecular Biology, Pomona College, Claremont, CAContributors: Max Wragan, Archie Spindler, Dr. EJ Crane, and Dr. Andre Cavalcanti

Plots of the scores of each environment in the first two principal components. Aerobic environments are shown in teal and anaerobic environments are shown in orange. The 95% confidence ellipses are also shown for each category.

Figure 1

Variable PCA with grouping. Each arrow represents a protein. The color of each arrow corresponds to the predicted function of the protein. Dimensions 2 and 3 were utilized, rather than the default Dimensions 1 and 2, to increase clarity of figure. CoADR and Npsr were found to group among known Elemental Sulfur Reducing Proteins—PsrA, SudHa, and SudHb—suggesting CoADR and Npsr also act as elemental sulfur reducers

Figure 2
Effects of a corn/bean‐based beverage on gastrointestinal symptoms in subjects with abdominal obesity
Authors: Gutiérrez-Salmeán Gabriela , Hernández-Ortega Marcela , Hernández-Hernández Cecilia , Ortega-Velázquez Sofía
Published: April 2020

Background

Inflammation underlying obesity has been linked to alterations in the gut‐brain axis, clinically manifesting, among others, as defects in intestinal motility thus gastrointestinal distress. Although diet therapy traditionally excludes foods with fermentable components such as corn and beans, it is proposed that some varieties of these have high contents of phytochemicals, such as polyphenols, capable of positively influencing symptomatology.

Objective

To assess the effect of a corn and bean‐based beverage on gastrointestinal symptoms in subjects with abdominal obesity.

Methods

We carried out a randomized placebo‐controlled clinical trial (CONBIOETICA approved) in which a beverage was given (supplement: chapalote (red) corn and ayocote (purple) beans, providing 100 mg EAG vs. placebo: white corn and beans) to subjects with abdominal obesity. Gastrointestinal symptoms, stool consistency and abdominal circumference, were assessed every two weeks, for 2 months. After determining the normality of data, an ANOVA for repeated measures with Tukey’s posthoc was performed for intragroup inferential analysis; the effects between treatments were compared with independent t‐Student. p<0.05 was considered as statistical significance.

Results

40 participants, mostly women, concluded the study. A statistically significant decrease in gastrointestinal symptoms was found in both groups over time; with no intergroup difference. In stool consistency, the supplement showed a statistically significant improvement. Both groups presented a significant decrease in abdominal circumference.

Conclusions

Corn and beans may contain elements other than polyphenols that improve gastrointestinal symptoms, so their exclusion from the diet in patients referring irritable bowel traits must be reconsidered.

Support or Funding Information

Universidad Anáhuac México (institutional research fund)

Changes in GI symptoms, stool consistency and abdominal circumference after 2‐month intervention.

Figure 1
Hayeobtan ameliorates high fat/high cholesterol diet‐induced hypertriglyceridemia and endothelial dysfunction
Authors: Kim Hye Yoom , Hong Mi Hyeon , Na Se Won , Jang Youn Jae , Cho Kyoung Woo , Kang Dae Gill , Lee Ho Sub
Published: April 2020

The leaves of lotus are called ‘Hayeob’ (
), which is known to have the effect of extinguishing heat, smoothing water metabolism, clearing the blood, and releasing blood(1–2). This experimental study was designed to investigate the inhibitory effects of Hayeobtan on lipid metabolism in high fat/cholesterol diet (HFCD)‐induced hypertriglyceridemia(3–4). Sprague Dawley rats were fed the HFCD diet with/without fluvastatin (Flu, positive control) 3 mg/kg/day, and HYT 100 or 200 mg/kg/day, respectively. All groups received a regular diet or HF diet, respectively, for 13 weeks. The last three groups treatment of Flu and HYT 100, and HYT200 orally for 9 weeks. Treatment of HYT markedly attenuated plasma levels of triglycerides and augmented plasma levels of high‐density lipoprotein (HDL) in HFCD‐fed rats. HYT and Flu also led to an increase in lipoprotein lipase activity in the HFCD group. On the other hand, HYT and Flu led to an decrease in fatty acid synthase and free fatty acid activity in the HFCD group. Treatment with HYT suppressed increased expressions of PPAR‐α and AMPK in HFCD rat liver or muscle. In addition, the HYT attenuated triglyceridemia by inhibition of PPAR‐γ and FABP protein expression levels and LXR and SREBP‐1 gene expression in liver or muscle. The HYT significantly prevented the development of the metabolic disturbances such as hypertriglyceridemia and hyperlipidemia. Taken together, the administration of HYT improves hypertriglyceridemia through the alteration in suppression of triglyceride synthesis and accentuated of triglyceride decomposition. These results suggested that HYT is useful in the prevention or treatment of hypertriglyceridemia‐related disorders such as triglyceride metabolism.

Support or Funding Information

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2017R1A5A2015805)(2019R1I1A3A01062432).
Opportunities to Improve Antibiotic Appropriateness in U.S. ICUs: A Multicenter Evaluation
Authors: Trivedi Kavita K. , Bartash Rachel , Letourneau Alyssa R. , Abbo Lilian , Fleisher Jorge , Gagliardo Christina , Kelley Shannon , Nori Priya , Rieg Gunter K. , Silver Phyllis , Srinivasan Arjun , Vargas Jaclyn , Ostrowsky Belinda ,   the Partnership for Quality Care (PQC) Inpatient Antimicrobial Stewardship Working Group
Published: April 2020

Objectives:

To use a standardized tool for a multicenter assessment of antibiotic appropriateness in ICUs and identify local antibiotic stewardship improvement opportunities.

Design:

Pilot point prevalence conducted on October 5, 2016; point prevalence survey conducted on March 1, 2017.

Setting:

ICUs in 12 U.S. acute care hospitals with median bed size 563.

Patients:

Receiving antibiotics on participating units on March 1, 2017.

Interventions:

The Centers for Disease Control and Prevention tool for the Assessment of Appropriateness of Inpatient Antibiotics was made actionable by an expert antibiotic stewardship panel and implemented across hospitals. Data were collected by antibiotic stewardship program personnel at each hospital, deidentified and submitted in aggregate for benchmarking. hospital personnel identified most salient reasons for inappropriate use by category and agent.

Measurements and Main Results:

Forty-seven ICUs participated. Most hospitals (83%) identified as teaching with median licensed ICU beds of 70. On March 1, 2017, 362 (54%) of 667 ICU patients were on antibiotics (range, 8–81 patients); of these, 112 (31%) were identified as inappropriate and administered greater than 72 hours among all 12 hospitals (range, 9–82%). Prophylactic antibiotic regimens and PICU patients demonstrated a statistically significant risk ratio of 1.76 and 1.90 for inappropriate treatment, respectively. Reasons for inappropriate use included unnecessarily broad spectrum (29%), no infection or nonbacterial syndrome (22%), and duration longer than necessary (21%). Of patients on inappropriate antibiotic therapy in surgical ICUs, a statistically significant risk ratio of 2.59 was calculated for noninfectious or nonbacterial reasons for inappropriate therapy.

Conclusions:

In this multicenter point prevalence study, 31% of ICU antibiotic regimens were inappropriate; prophylactic regimens were often inappropriate across different ICU types, particularly in surgical ICUs. Engaging intensivists in antibiotic stewardship program efforts is crucial to sustain the efficacy of antibiotics and quality of infectious diseases care in critical care settings. This study underscores the value of standardized assessment tools and benchmarking to be shared with local leaders for targeted antibiotic stewardship program interventions.
Whole-genome analysis across 10 songbird families within Sylvioidea reveals a novel autosome–sex chromosome fusion
Authors: Sigeman Hanna , Ponnikas Suvi , Hansson Bengt
Published: April 2020

Sex chromosomes in birds have long been considered to be extremely stable. However, this notion has lately been challenged by findings of independent autosome–sex chromosome fusions within songbirds, several of which occur within a single clade, the superfamily Sylvioidea. To understand what ecological and evolutionary processes drive changes in sex chromosome systems, we need complete descriptions of sex chromosome diversity across taxonomic groups. Here, we characterize the sex chromosome systems across Sylvioidea using whole-genome data of species representatives of 10 different families, including two published and eight new genomes. We describe a novel fusion in the family Cisticolidae (represented by
Cisticola juncidis
) involving a part of chromosome 4. We also confirm the previously identified fusion between chromosome Z and a part of chromosome 4A in all 10 families and show that fusions involving parts of chromosomes 3 and 5 are not found outside the families where they were first discovered (Alaudidae and Panuridae). These findings add to the complexity of the sex chromosome system in Sylvioidea, where four independent autosome–sex chromosome fusions have now been identified.
Optimal control approaches for combining medicines and mosquito control in tackling dengue
Authors: Rawson Thomas , Wilkins Kym E. , Bonsall Michael B.
Published: April 2020

Dengue is a debilitating and devastating viral infection spread by mosquito vectors, and over half the world’s population currently live at risk of dengue (and other flavivirus) infections. Here, we use an integrated epidemiological and vector ecology framework to predict optimal approaches for tackling dengue. Our aim is to investigate how vector control and/or vaccination strategies can be best combined and implemented for dengue disease control on small networks, and whether these optimal strategies differ under different circumstances. We show that a combination of vaccination programmes and the release of genetically modified self-limiting mosquitoes (comparable to sterile insect approaches) is always considered the most beneficial strategy for reducing the number of infected individuals, owing to both methods having differing impacts on the underlying disease dynamics. Additionally, depending on the impact of human movement on the disease dynamics, the optimal way to combat the spread of dengue is to focus prevention efforts on large population centres. Using mathematical frameworks, such as optimal control, are essential in developing predictive management and mitigation strategies for dengue disease control.
Facile fabrication of Mn
2+
-doped ZnO photocatalysts by electrospinning
Authors: Wang Yuting , Hao Xin , Wang Zegao , Dong Mingdong , Cui Lifeng
Published: April 2020

In this study, a high-efficiency photocatalyst was synthesized by Mn
2+
-doped ZnO nanofibres (NFs) fabricated by facile electrospinning and a following annealing process, in which Mn
2+
successes incorporate to ZnO NFs lattice without changing any morphology and crystalline structure of ZnO. The photodegradation properties of ZnO loading with different concentrations of Mn
2+
(5, 10, 15 and 50 at%) were investigated. The 50% MnO–ZnO composite owns excellent active photocatalytic performance (quantum efficiency up to 7.57%) compared to pure ZnO (0.16%) under visible light and can be considered as an efficient visible light photocatalyst material. We systematically analysed its catalytic mechanism and found that the enhancement belongs to the Mn doping effect and the phase junction between MnO and ZnO. The dominant mechanism of Mn doping leads to the presence of impurity levels in the band gap of ZnO, narrowing the optical band gap of ZnO. In addition, doped Mn
2+
ions can be used as electron traps that inhibit the recombination process and promote electron–hole pair separation. In summary, this paper provides a convenient method for fabricating highly efficient visible light photocatalysts using controlled annealing.
Experimental investigation on combustion characteristics of flammable refrigerant R290/R1234yf leakage from heat pump system for electric vehicles
Authors: Li Kang , Wang Jingwu , Luo Shuxian , Wang Zhenzhen , Zhou Xuejin , Fang Jun , Su Lin , Tu Ran
Published: April 2020

Concerning the issues regarding driving mileage reduction for electric vehicles (EVs) in cold climates, a heat pump system with low global warming potential refrigerant R290/R1234yf is employed as one of the promising solutions. Different from the widely used mobile refrigerant R134a, R290 and R1234yf are both flammable or explosive. The application of R290/R1234yf in the mobile heat pump system is hindered by unexpected refrigerant leakage with the existence of fire and explosion risk. In this study, the combustion characteristics of R290/R1234yf in a potential leakage process from an air-conditioning heat pump system for EVs were investigated. Firstly, thermodynamic behaviours of R290/R1234yf used in a typical heat pump system were analysed based on a special experimental facility designed for EVs. Then the leakage and combustion characteristics of R290/R1234yf including flame shape, temperature, radiation etc. were obtained by the experimental method under different initial temperature and mass flow rate conditions. It was found that R290/R1234yf leaked is difficult to ignite at low temperatures, while the blow-off phenomenon of the jet flame would occur at high temperature with high leakage mass flow rate. In addition, the results showed that combustion intensity would be enhanced by the leakage mass flow rate between 30 and 60°C. These results could provide guidance for fire detection and rescue system design for new energy vehicles.
Enhanced magnetic performance of aligned wires assembled from nanoparticles: from nanoscale to macroscale
Authors: Li Qing , Kartikowati Christina W. , Iwaki Toru , Okuyama Kikuo , Ogi Takashi
Published: April 2020

Magnetic wires in highly dense arrays, possessing unique magnetic properties, are eagerly anticipated for inexpensive and scalable fabrication technologies. This study reports a facile method to fabricate arrays of magnetic wires directly assembled from well-dispersed α
″
-Fe
16
N
2
/Al
2
O
3
and Fe
3
O
4
nanoparticles with average diameters of 45 nm and 65 nm, respectively. The magnetic arrays with a height scale of the order of 10 mm were formed on substrate surfaces, which were perpendicular to an applied magnetic field of 15 T. The applied magnetic field aligned the easy axis of the magnetic nanoparticles (MNPs) and resulted in a significant enhancement of the magnetic performance. Hysteresis curves reveal that values of magnetic coercivity and remanent magnetization in the preferred magnetization direction are both higher than that of the nanoparticles, while these values in the perpendicular direction are both lower. Enhancement in the magnetic property for arrays made from spindle-shape α
″
-Fe
16
N
2
/Al
2
O
3
nanoparticles is higher than that made from cube-like α
″
-Fe
16
N
2
/Al
2
O
3
ones, owing to the shape anisotropy of MNPs. Furthermore, the assembled highly magnetic α
″
-Fe
16
N
2
/Al
2
O
3
arrays produced a detectable magnetic field with an intensity of approximately 0.2 T. Although high-intensity external field benefits for the fabrication of magnetic arrays, the newly developed technique provides an environmentally friendly and feasible approach to fabricate magnetic wires in highly dense arrays in open environment condition.
Operating at the extreme: estimating the upper yield boundary of winter wheat production in commercial practice
Authors: Mitchell Emily G. , Crout Neil M. J. , Wilson Paul , Wood Andrew T. A. , Stupfler Gilles
Published: April 2020

Wheat farming provides 28.5% of global cereal production. After steady growth in average crop yield from 1950 to 1990, wheat yields have generally stagnated, which prompts the question of whether further improvements are possible. Statistical studies of agronomic parameters such as crop yield have so far exclusively focused on estimating parameters describing the whole of the data, rather than the highest yields specifically. These indicators include the mean or median yield of a crop, or finding the combinations of agronomic traits that are correlated with increasing average yields. In this paper, we take an alternative approach and consider high yields only. We carry out an extreme value analysis of winter wheat yield data collected in England and Wales between 2006 and 2015. This analysis suggests that, under current climate and growing conditions, there is indeed a finite upper bound for winter wheat yield, whose value we estimate to be 17.60 tonnes per hectare. We then refine the analysis for strata defined by either location or level of use of agricultural inputs. We find that there is no statistical evidence for variation of maximal yield depending on location, and neither is there statistical evidence that maximum yield levels are improved by high levels of crop protection and fertilizer use.
Metabolic rate in common shrews is unaffected by temperature, leading to lower energetic costs through seasonal size reduction
Authors: Schaeffer Paul J. , O'Mara M. Teague , Breiholz Japhet , Keicher Lara , Lázaro Javier , Muturi Marion , Dechmann Dina K. N.
Published: April 2020

Small endothermic mammals have high metabolisms, particularly at cold temperatures. In the light of this, some species have evolved a seemingly illogical strategy: they reduce the size of the brain and several organs to become even smaller in winter. To test how this morphological strategy affects energy consumption across seasonally shifting ambient temperatures, we measured oxygen consumption and behaviour in the three seasonal phenotypes of the common shrew (
Sorex araneus
), which differ in size by about 20%. Body mass was the main driver of oxygen consumption, not the reduction of metabolically expensive brain mass. Against our expectations, we found no change in relative oxygen consumption with low ambient temperature. Thus, smaller body size in winter resulted in significant absolute energy savings. This finding could only partly be explained by an increase of lower cost behaviours in the activity budgets. Our findings highlight that these shrews manage to avoid one of the most fundamental and intuitive rules of ecology, allowing them to subsist with lower resource availability and successfully survive the harsh conditions of winter.
Organic residue analysis shows sub-regional patterns in the use of pottery by Northern European hunter–gatherers
Authors: Courel Blandine , Robson Harry K. , Lucquin Alexandre , Dolbunova Ekaterina , Oras Ester , Adamczak Kamil , Andersen Søren H. , Astrup Peter Moe , Charniauski Maxim , Czekaj-Zastawny Agnieszka , Ezepenko Igor , Hartz Sönke , Kabaciński Jacek , Kotula Andreas , Kukawka Stanisław , Loze Ilze , Mazurkevich Andrey , Piezonka Henny , Piličiauskas Gytis , Sørensen Søren A. , Talbot Helen M. , Tkachou Aleh , Tkachova Maryia , Wawrusiewicz Adam , Meadows John , Heron Carl P. , Craig Oliver E.
Published: April 2020

The introduction of pottery vessels to Europe has long been seen as closely linked with the spread of agriculture and pastoralism from the Near East. The adoption of pottery technology by hunter–gatherers in Northern and Eastern Europe does not fit this paradigm, and its role within these communities is so far unresolved. To investigate the motivations for hunter–gatherer pottery use, here, we present the systematic analysis of the contents of 528 early vessels from the Baltic Sea region, mostly dating to the late 6th–5th millennium cal BC, using molecular and isotopic characterization techniques. The results demonstrate clear sub-regional trends in the use of ceramics by hunter–gatherers; aquatic resources in the Eastern Baltic, non-ruminant animal fats in the Southeastern Baltic, and a more variable use, including ruminant animal products, in the Western Baltic, potentially including dairy. We found surprisingly little evidence for the use of ceramics for non-culinary activities, such as the production of resins. We attribute the emergence of these sub-regional cuisines to the diffusion of new culinary ideas afforded by the adoption of pottery, e.g. cooking and combining foods, but culturally contextualized and influenced by traditional practices.
Design, synthesis, molecular modelling andin vitroscreening of monoamine oxidase inhibitory activities of novel quinazolyl hydrazine derivatives
Authors: Amer Adel , Hegazi Abdelrahman H. , Alshekh Mohammed Khalil , Ahmed Hany E. A. , Soliman Saied M. , Maniquet Antonin , Ramsay Rona R.
Published: April 2020

A new series of N'-substituted benzylidene-2-(4-oxo-2-phenyl-1,4-dihydroquinazolin-3(2H)-yl)acetohydrazide (5a–5h) has been synthesized, characterized by FT-IR, NMR spectroscopy and mass spectrometry and tested against human monoamine oxidase (MAO) A and B. Only (4-hydroxy-3-methoxybenzylidene) substituted compounds gave submicromolar inhibition of MAO-A and MAO-B. Changing the phenyl substituent to methyl on the unsaturated quinazoline ring (12a–12d) decreased inhibition, but a less flexible linker (14a–14d) resulted in selective micromolar inhibition of hMAO-B providing insight for ongoing design.
Experimental and numerical investigation of the fatigue behaviour and crack evolution mechanism of granite under ultra-high-frequency loading
Authors: Zhou Yu , Zhao Dajun , Tang Qiongqiong , Wang Meiyan
Published: April 2020

Assisted ultrasonic vibration technology has received great interest in the past few years for petroleum and mining engineering related to hard rock breaking. Understanding the fatigue behaviour and damage characteristics of rock subject to ultra-high-frequency loading is vital for its application. In this research, we conducted ultrasonic vibration breaking rock experiments combined with an ultra-dynamic data receiver and strain gauges to monitor the development of strain in real time. The experimental results show that the strain curve is U-shaped, and it can be divided into three stages: the strain first decreases, then remains steady (with light fluctuations) and finally increases. The sample first underwent compressive deformation, and no rupture occurred. As the vibration continued, the compressive deformation decreased with the initiation and propagation of cracks, and fragmentation occurred. To elucidate the crack evolution mechanism of the granite specimens, numerical simulations were performed using particle flow code in two dimensions (PFC2D), and an improved fatigue damage model based on the flat-joint contact model was proposed. The numerical results indicate that this model can effectively reproduce the fatigue characteristics of hard brittle rocks under ultrasonic vibration. By analysing the stress and strain fields and cracking process, the crack evolution mechanism in the brittle hard rock under ultra-high-frequency loading is revealed. These experimental and numerical results are expected to improve the understanding of the fragmentation mechanism of rock under assisted ultrasonic vibration.
Diet composition and social environment determine food consumption, phenotype and fecundity in an omnivorous insect
Authors: Gutiérrez Yeisson , Fresch Marion , Ott David , Brockmeyer Jens , Scherber Christoph
Published: April 2020

Nutrition is the single most important factor for individual's growth and reproduction. Consequently, the inability to reach the nutritional optimum imposes severe consequences for animal fitness. Yet, under natural conditions, organisms may face a mixture of stressors that can modulate the effects of nutritional asymmetry. For instance, stressful environments caused by intense interaction with conspecifics. Here, we subjected the house cricketAcheta domesticusto (i) either of two types of diet that have proved to affect cricket performance and (ii) simultaneously manipulated their social environment throughout their complete life cycle. We aimed to track sex-specific consequences for multiple traits during insect development throughout all life stages. Both factors affected critical life-history traits with potential population-level consequences: diet composition induced strong effects on insect development time, lifespan and fitness, while the social environment affected the number of nymphs that completed development, food consumption and whole-body lipid content. Additionally, both factors interactively determined female body mass. Our results highlight that insects may acquire and invest resources in a different manner when subjected to an intense interaction with conspecifics or when isolated. Furthermore, while only diet composition affected individual reproductive output, the social environment would determine the number of reproductive females, thus indirectly influencing population performance.
Nonlinear stability of two-layer shallow water flows with a free surface
Authors: de Melo Viríssimo Francisco , Milewski Paul A.
Published: April 2020

The problem of two layers of immiscible fluid, bordered above by an unbounded layer of passive fluid and below by a flat bed, is formulated and discussed. The resulting equations are given by a first-order, four-dimensional system of PDEs of mixed-type. The relevant physical parameters in the problem are presented and used to write the equations in a non-dimensional form. The conservation laws for the problem, which are known to be only six, are explicitly written and discussed in both non-Boussinesq and Boussinesq cases. Both dynamics and nonlinear stability of the Cauchy problem are discussed, with focus on the case where the upper unbounded passive layer has zero density, also called the free surface case. We prove that the stability of a solution depends only on two ‘baroclinic’ parameters (the shear and the difference of layer thickness, the former being the most important one) and give a precise criterion for the system to be well-posed. It is also numerically shown that the system is nonlinearly unstable, as hyperbolic initial data evolves into the elliptic region before the formation of shocks. We also discuss the use of simple waves as a tool to bound solutions and preventing a hyperbolic initial data to become elliptic and use this idea to give a mathematical proof for the nonlinear instability.
Coexisting attractors in the context of cross-scale population dynamics: measles in London as a case study
Authors: Becker Alexander D. , Zhou Susan H. , Wesolowski Amy , Grenfell Bryan T.
Published: April 2020

Patterns of measles infection in large urban populations have long been considered the paradigm of synchronized nonlinear dynamics. Indeed, recurrent epidemics appear approximately mass-action despite underlying heterogeneity. However, using a subset of rich, newly digitized mortality data (1897–1906), we challenge that proposition. We find that sub-regions of London exhibited a mixture of simultaneous annual and biennial dynamics, while the aggregate city-level dynamics appears firmly annual. Using a simple stochastic epidemic model and maximum-likelihood inference methods, we show that we can capture this observed variation in periodicity. We identify agreement between theory and data, indicating that both changes in periodicity and epidemic coupling between regions can follow relatively simple rules; in particular we find local variation in seasonality drives periodicity. Our analysis underlines that multiple attractors can coexist in a strongly mixed population and follow theoretical predictions.
Optimizing adaptive cancer therapy: dynamic programming and evolutionary game theory
Authors: Gluzman Mark , Scott Jacob G. , Vladimirsky Alexander
Published: April 2020

Recent clinical trials have shown that adaptive drug therapies can be more efficient than a standard cancer treatment based on a continuous use of maximum tolerated doses (MTD). The adaptive therapy paradigm is not based on a preset schedule; instead, the doses are administered based on the current state of tumour. But the adaptive treatment policies examined so far have been largely ad hoc. We propose a method for systematically optimizing adaptive policies based on an evolutionary game theory model of cancer dynamics. Given a set of treatment objectives, we use the framework of dynamic programming to find the optimal treatment strategies. In particular, we optimize the total drug usage and time to recovery by solving a Hamilton–Jacobi–Bellman equation. We compare MTD-based treatment strategy with optimal adaptive treatment policies and show that the latter can significantly decrease the total amount of drugs prescribed while also increasing the fraction of initial tumour states from which the recovery is possible. We conclude that the use of optimal control theory to improve adaptive policies is a promising concept in cancer treatment and should be integrated into clinical trial design.
Behavioural traits modulate the use of heterospecific social information for nest site selection: experimental evidence from a wild bird population
Authors: Morinay Jennifer , Forsman Jukka T. , Germain Marion , Doligez Blandine
Published: April 2020

The use of social information for making decisions is common but can be constrained by behavioural traits via, for example, the ability to gather information. Such constrained information use has been described in foraging habitat selection; yet it remains unexplored in the breeding habitat selection context, despite potentially strong fitness consequences. We experimentally tested whether three behavioural traits (aggressiveness, boldness and neophobia) affected the use of heterospecific social information for nest site selection in wild collared flycatchers
Ficedula albicollis
. Flycatchers have previously been found to copy or reject an artificial apparent preference of tits (their main competitors) for a nest site feature: they preferred nest-boxes with the same or a different feature, depending on tit early reproductive investment. Here, we confirmed this result and showed that shy individuals and less aggressive old males (i.e. 2 years old or older) copied tit apparent preference, while more aggressive old males rejected the tit preference. Aggressiveness and boldness may allow males to access more information sources or affect males' interactions with dominant tits when selecting a nest site. Our study highlights the links between variation in behaviours and social information use for breeding habitat selection and calls for further work to explore underlying mechanisms.
A Randomized, Single-blind, Group sequential, Active-controlled Study to evaluate the clinical efficacy and safety of α-Lipoic acid for critically ill patients with coronavirus disease 2019(COVID-19)
Authors: Zhong Ming , Sun Aijun , Xiao Ting , Yao Ge , Sang Ling , Zheng Xia , Zhang Jinyan , Jin Xuejuan , Xu Lei , Yang Wenlong , Wang Peng , Hu Kai , Zhang Dingyu , Ge Junbo
Published: April 2020

Object

To evaluate the clinical efficacy and safety of α-Lipoic acid (ALA) for critically ill patients with coronavirus disease 2019 (COVID-19).

Methods

A randomized, single-blind, group sequential, active-controlled trial was performed at JinYinTan Hospital, Wuhan, China. Between February 2020 and March 2020, 17 patients with critically ill COVID-19 were enrolled in our study. Eligible patients were randomly assigned in a 1:1 ratio to receive either ALA (1200 mg/d, intravenous infusion) once daily plus standard care or standard care plus equal volume saline infusion (placebo) for 7 days. All patients were monitored within the 7 days therapy and followed up to day 30 after therapy. The primary outcome of this study was the Sequential Organ Failure Estimate (SOFA) score, and the secondary outcome was the all-cause mortality within 30 days.

Result

Nine patients were randomized to placebo group and 8 patients were randomized to ALA group. SOFA score was similar at baseline, increased from 4.3 to 6.0 in the placebo group and increased from 3.8 to 4.0 in the ALA group (P=0.36) after 7 days. The 30-day all-cause mortality tended to be lower in the ALA group (3/8, 37.5%) compared to that in the placebo group (7/9, 77.8%, P=0.09).

Conclusion

In our study, ALA use is associated with lower SOFA score increase and lower 30-day all-cause mortality as compared with the placebo group. Although the mortality rate was two-folds higher in placebo group than in ALA group, only borderline statistical difference was evidenced due to the limited patient number. Future studies with larger patient cohort are warranted to validate the role of ALA in critically ill patients with COVID-19.