bluuebunny/crossref_metadata_2025 huggingface dataset:
5. indlæg: Nye statistikværktøjer
Authors: Iversen Rie Karen Marie
Published: June 2021

Her kan du se det femte indlæg, der blev vist på vores webinar 10. juni 2021
Stability of neocortical synapses across sleep and wake states during the critical period in rats
Authors: Cary Brian A , Turrigiano Gina G
Published: June 2021

Sleep is important for brain plasticity, but its exact function remains mysterious. An influential but controversial idea is that a crucial function of sleep is to drive widespread downscaling of excitatory synaptic strengths. Here, we used real-time sleep classification, ex vivo measurements of postsynaptic strength, and in vivo optogenetic monitoring of thalamocortical synaptic efficacy to ask whether sleep and wake states can constitutively drive changes in synaptic strength within the neocortex of juvenile rats. We found that miniature excitatory postsynaptic current amplitudes onto L4 and L2/3 pyramidal neurons were stable across sleep- and wake-dense epochs in both primary visual (V1) and prefrontal cortex (PFC). Further, chronic monitoring of thalamocortical synaptic efficacy in V1 of freely behaving animals revealed stable responses across even prolonged periods of natural sleep and wake. Together, these data demonstrate that sleep does not drive widespread downscaling of synaptic strengths during the highly plastic critical period in juvenile animals. Whether this remarkable stability across sleep and wake generalizes to the fully mature nervous system remains to be seen.
Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice
Authors: Ryu Seungjin , Shchukina Irina , Youm Yun-Hee , Qing Hua , Hilliard Brandon , Dlugos Tamara , Zhang Xinbo , Yasumoto Yuki , Booth Carmen J , Fernández-Hernando Carlos , Suárez Yajaira , Khanna Kamal , Horvath Tamas L , Dietrich Marcelo O , Artyomov Maxim , Wang Andrew , Dixit Vishwa Deep
Published: June 2021

Increasing age is the strongest predictor of risk of COVID-19 severity and mortality. Immunometabolic switch from glycolysis to ketolysis protects against inflammatory damage and influenza infection in adults. To investigate how age compromises defense against coronavirus infection, and whether a pro-longevity ketogenic diet (KD) impacts immune surveillance, we developed an aging model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain-A59 (MHV-A59). When inoculated intranasally, mCoV is pneumotropic and recapitulates several clinical hallmarks of COVID-19 infection. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue, and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Activation of ketogenesis in aged mice expands tissue protective γδ T cells, deactivates the NLRP3 inflammasome, and decreases pathogenic monocytes in lungs of infected aged mice. These data establish harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against coronavirus infection in the aged.
Relationship between Body Mass Index and Flexibility in Young Adults
Authors: Gite Ashwini Akash , Mukkamala Neha , Parmar Lata
Published: June 2021

BACKGROUND: Flexibility is important for general health and fitness, athletic performance, injury prevention and rehabilitation. Sedentary behavior of students leads to decreased physical fitness levels which affects flexibility. There is little evidence regarding relationship between BMI and flexibility.

Aim: To study the relationship between BMI and flexibility and BMI and physical activity in young adults.

Study Design: Observational study

Place and Duration Of Study: The study was carried out at College of Physiotherapy, Sumandeep Vidyapeeth, Vadodara from September 2019 to March 2020.

Methods: Males and females between 18 to 30 years were included in the study. BMI, Sit and Reach Test for low back and hamstring flexibility, Active Knee Extension Test (AKET) for hamstrings and Global Physical Activity Questionnaire (GPAQ) for physical activity levels were assessed.

Results: 570 participants with mean age of 20.23±2.07 years were included. Mean BMI was 21.83±4.81 kg/m2. Number of females were 462 and males were 108. There was no significant correlation between BMI and flexibility of low back (P=.247) and hamstring (Rt) (P=.668) (Lt) (P=.354). BMI and GPAQ showed a statistically significant association (P=0.02). There was a weak positive correlation which was statistically significant between GPAQ and SART (P =0.000) and a weak negative correlation which was statistically significant between GPAQ and Rt AKET (P=0.004).

Conclusion:  There was no significant correlation found between BMI and flexibility. There was a statistically significant association between BMI and physical activity, a weak negative correlation between GPAQ and hamstring flexibility and weak positive correlation between GPAQ and SART.
Encapsulation Technologies of Plant Growth‐Promoting Microorganisms and Microbial Biological Control Agents Against Plant Pathogenic Organisms
Authors: Marcial‐Coba Martín S. , Soria‐Delgado Lucía , Yánez‐Altuna Jeniffer M.
Published: June 2021

As a function of the global necessity to reduce or replace the use of chemical fertilisers and pesticides, due to their toxicity, the formulation of microbial inoculants has been suggested as an environmentally friendly alternative for maintaining crop production at economically sustainable levels. In this connection, the microencapsulation of beneficial soil‐borne microorganisms is conceived as a strategy to improve the inoculant's efficiency, in terms of viability and functionality. In this article, we describe the most widely applied microencapsulation techniques, including the mechanisms and wall materials involved, as well as the advantages and shortcomings of using different encapsulation technologies. Moreover, the desiccation technologies used as a tool to extend the shelf‐life of immobilised microbes are also explained. Finally, the outcomes of various, relatively recent studies regarding the encapsulation of plant growth‐promoting microorganisms and biocontrol agents, including bacteriophages, are discussed. This article may contribute to the design of microbial inoculant delivery strategies, aiming to increase crop production and to reduce the utilisation of chemical fertilisers and pesticides.
Commissioning of and preliminary experience with a new fully integrated computed tomography linac
Authors: Yu Lei , Zhao Jun , Zhang Zhen , Wang Jiazhou , Hu Weigang
Published: June 2021

Purpose

A new medical linear accelerator (linac) platform integrated with helical computed tomography (CT), the uRT‐linac 506c, was introduced into clinical application in 2019 by United Imaging Healthcare (UIH) Co., Ltd. (Shanghai, China). It combines a Carm linac with a diagnostic‐quality 16‐slice CT imager, providing seamless workflow from simulation to treatment. The aim of this report is to assess the technical characteristics, commissioning results and preliminary experiences stemming from clinical usage.

Methods

The mechanical and imaging test procedures, commissioning data collection and TPS validation were summarized. CTIGRT accuracy was investigated with different loads and couch extensions. A series of end‐to‐end cases for different treatment sites and delivery techniques were tested preclinically to estimate the overall accuracy for the entire treatment scheme. The results of patient‐specific QA and machine stability during a one‐year operation are also reported.

Results

Gantry/couch/collimator isocentricity was measured as 0.63 mm in radius. The TPS models were in agreement with the beam commissioning data within a deviation of 2%. An overall submillimeter accuracy was demonstrated for the CT‐IGRT process under all conditions. The absolute point dose difference for all the preclinical end‐to‐end tests was within 3%, and the gamma passing rate of the 2D dose distribution measured by EBT3 film was better than 90% (3% DD, 3 mm DTA and 10% threshold). Pretreatment QA of clinical cases resulted with better than 3% point dose difference and more than 99% gamma passing rate (3% DD/2 mm DTA/10% threshold) tested with Delta4. The output of the linac was mostly within 1% of variation in a one‐year operation.

Conclusion

The commissioning results and clinical QA results show that the uRT‐linac 506c platform exhibits good and stable performance in mechanical and dosimetric accuracy. The integrated CT system provides an efficient workflow for image guidance with submillimeter localization precision, and will be a good starting point to proceed advanced adaptive radiotherapy.
Muscle Strength and Osteoarthritis Progression After Surgery or Exercise for Degenerative Meniscal Tears: Secondary Analyses of a Randomized Trial
Authors: Berg Bjørnar , Roos Ewa M. , Kise Nina Jullum , Engebretsen Lars , Holm Inger , Risberg May Arna
Published: June 2021

Objective

To evaluate muscle strength changes following partial meniscectomy or exercise therapy for degenerative meniscal tears and the relationship between baseline muscle strength and osteoarthritis progression.

Methods

Secondary analysis of a randomized trial (n = 140 participants). Isokinetic quadriceps and hamstrings strength (peak torque [Nm/kg] and total work [J/kg]) were assessed at baseline, 3‐month, 12‐month, and 5‐year follow‐up. Between‐group differences were analyzed using intent‐to‐treat linear mixed models. The relationship between baseline muscle strength and osteoarthritis progression (Kellgren/Lawrence ≥1 grade increase) were assessed using logistic regression models.

Results

We found statistically significant between‐group differences favoring exercise therapy at 3 months (quadriceps –0.30 Nm/kg [95% confidence interval (95% CI) –0.40, –0.20]; hamstrings –0.10 Nm/kg [95% CI –0.15, –0.04]) and 12 months (quadriceps –0.13 Nm/kg [95% CI –0.23, –0.03]; hamstrings –0.08 Nm/kg [95% CI –0.14, –0.03]). At 5 years, between‐group differences were –0.10 Nm/kg (95% CI –0.21, 0.01) for quadriceps and –0.07 Nm/kg (95% CI –0.13, –0.01) for hamstrings. Quadriceps muscle weakness at baseline was associated with knee osteoarthritis progression over 5 years, with adjusted odds ratio of 1.40 for every 0.2 Nm/kg decrease (95% CI 1.15, 1.71). The adjusted odds ratio for hamstrings was 1.14 (95% CI 0.97, 1.35) for every 0.1 Nm/kg decrease.

Conclusion

Exercise therapy was effective in improving muscle strength at 3‐ and 12‐month follow‐up compared to partial meniscectomy, but the effect was attenuated at 5 years. Quadriceps muscle weakness at baseline was associated with higher odds of osteoarthritis progression over 5 years.
Leather‐Based Multi‐Stimuli Responsive Chromisms
Authors: Jia Lu , Zeng Songshan , Ding Hao , Smith Andrew T. , LaChance Anna Marie , Farooqui Maria M. , Gao Dangge , Ma Jianzhong , Sun Luyi
Published: June 2021

Leather is made from the skin of animals and possesses special micro‐ and nanostructures. Due to the high breathability, durability, strength, elasticity, and softness, leather is widely used in daily life, and is an ideal substrate for future multi‐functional wearable smart devices. Herein, two leather‐based multi‐stimuli responsive chromic devices denoted as UV/thermo/electro chromic device and UV sensor are developed. The UV/thermo/electro chromic device demonstrates instantaneous and reversible chromic responses to applied UV radiation, heat, and electrical voltage with different color changing styles. The pattern design with the assistance of 3D printed molds and the broad selection of dyes/pigments endow the device with high design flexibility and wide applicability. The leather‐based UV sensor exhibits a change in color gradient when exposed to UV radiation with different intensities. For more versatile color options, inactive pigments/dyes can be mixed with stimuli‐responsive ones in this system. Coating the leather surface with a polyacrylic finishing agent is also conducted, which is a practical and effective method to protect the pigments and/or dyes in the leather, and improves the usability/durability of the devices. This study opens a new avenue to design and develop wearable devices and individual customization/anti‐counterfeiting of leather products.
High‐Performance Flexible Pressure Sensor Based on Controllable Hierarchical Microstructures by Laser Scribing for Wearable Electronics
Authors: Du Qifeng , Liu Lanlan , Tang Ruitao , Ai Jun , Wang Zhijian , Fu Qiqi , Li Chongxiao , Chen Ying , Feng Xue
Published: June 2021

Flexible pressure sensors are attracting considerable attention due to their potential applications in human health monitoring and human‐machine interfaces. However, it is hard to achieve both high sensitivity and wide linear detection range, and the complicated fabrication process restricts their practical applications. Herein, a simple and scalable fabrication process for a flexible pressure sensor with high sensitivity and wide detection range has been developed by combining the silver nanowires coated, laser‐ablated hierarchical microstructured polydimethylsiloxane, and an interdigital electrode. The hierarchical microstructures contribute to the high sensitivity of 4.48 kPa−1 and increase detection range from 0 to 65 kPa. The increase in the contact area and subsequent additional contact sites of the hierarchical microstructures lead to the high‐performance. Arterial pulse, breathing, and static tremors have been measured by attaching the device to the human body. Moreover, a pressure sensor array has been fabricated to illustrate the scalability of this strategy. The results demonstrate that the flexible pressure sensor with simple and scalable fabrication capability has promising applications in wearable electronic skins.
Focal Adhesion Kinase (FAK) Inhibition Synergizes with KRAS G12C Inhibitors in Treating Cancer through the Regulation of the FAK–YAP Signaling
Authors: Zhang Baoyuan , Zhang Yan , Zhang Jiangwei , Liu Ping , Jiao Bo , Wang Zaiqi , Ren Ruibao
Published: June 2021

KRAS mutation is one of the most prevalent genetic drivers of cancer development, yet KRAS mutations are until very recently considered undruggable. There are ongoing trials of drugs that target the KRAS G12C mutation, yet acquired drug resistance from the extended use has already become a major concern. Here, it is demonstrated that KRAS G12C inhibition induces sustained activation of focal adhesive kinase (FAK) and show that a combination therapy comprising KRAS G12C inhibition and a FAK inhibitor (IN10018) achieves synergistic anticancer effects. It can simultaneously reduce the extent of drug resistance. Diverse CDX and PDX models of KRAS G12C mutant cancer are examined and synergistic benefits from the combination therapy are consistently observed. Mechanistically, it is found that both aberrant FAK–YAP signaling and FAK‐related fibrogenesis impact on the development of KRAS G12C inhibitor resistance. This study thus illustrates the mechanism of resistance of cancer to the treatment of KRAS G12C inhibitor, as well as an innovative combination therapy to improve treatment outcomes for KRAS G12C mutant cancers.
Von geordneten zu mobilen Molekülen durch Kühlen
Authors: Aeschlimann Simon , Lyu Lu , Becker Sebastian , Mousavion Sina , Speck Thomas , Elmers Hans‐Joachim , Stadtmüller Benjamin , Aeschlimann Martin , Bechstein Ralf , Kühnle Angelika
Published: June 2021

Phasenübergänge zwischen unterschiedlichen Aggregatzuständen sind in Natur und Technik allgegenwärtig. Üblicherweise schmilzt ein Kristall, wenn er erwärmt wird. Daher nutzen wir Eis, um einen Drink zu kühlen. Bereits im Jahre 1903 spekulierte Gustav Tammann über den umgekehrten Prozess des Schmelzens durch Kühlen. Bisher gibt es allerdings nur sehr wenige Beispiele für solche “inversen” Phasenübergänge, die meist auch auf extreme Bedingungen beschränkt sind. Hier zeigen wir einen inversen Phasenübergang von adsorbierten Molekülen auf einer Oberfläche. Molybdänacetat bildet bei Zimmertemperatur eine geordnete Struktur auf der (111)‐Oberfläche von Kupfer, die sich beim Kühlen auflöst. Dieser Übergang entsteht dadurch, dass die Moleküle mobil werden, d. h., wir beobachten die Mobilisierung durch Kühlen. Dieses unerwartete Phänomen kann durch die große Zahl an internen Freiheitsgraden der geordneten Phase im Vergleich zur mobilen Phase erklärt werden.
Multicatalytic Transformation of (Meth)acrylic Acids: a One‐Pot Approach to Biobased Poly(meth)acrylates
Authors: Fouilloux Hugo , Qiang Wei , Robert Carine , Placet Vincent , Thomas Christophe M.
Published: June 2021

Shifting from petrochemical feedstocks to renewable resources can address some of the environmental issues associated with petrochemical extraction and make plastics production sustainable. Therefore, there is a growing interest in selective methods for transforming abundant renewable feedstocks into monomers suitable for polymer production. Reported herein are one‐pot catalytic systems, that are active, productive, and selective under mild conditions for the synthesis of copolymers from renewable materials. Each system allows for anhydride formation, alcohol acylation and/or acid esterification, as well as polymerization of the formed (meth)acrylates, providing direct access to a new library of unique poly(meth)acrylates.
Increasing chemisorbed silane coupling agents in surface‐treated layer of silica particles
Authors: Nakamura Takashi , Tsutsumi Ryota , Hashiguchi Chisato , Terao Toshiki , Manabe Kei , Hirai Tomoyasu , Fujii Syuji , Nakamura Yoshinobu
Published: June 2021

In the surface treated inorganic particles with silane coupling agent (SCA), chemisorbed and physisorbed molecules are present in the treated layer. Increasing the amount of chemisorption by increasing the molecular weight of SCAs was investigated. Oligomers formed via self‐condensation during storage more than 10 days at room temperature for 3‐methacryloxypropyltrimethoxysilane‐treated silica particles. Monomeric SCA evaporates easily by heating. The oligomers restrict evaporation, and heating increases the chemisorption. The influence of molecular weight of SCA was investigated. In the case of amino group, the amount of chemisorbed was greater for aminoethylaminooctyltrimethoxysilane with high molecular weight than for 3‐aminopropyltriethoxysilane. For SCAs with hydrocarbon chains, the amount of chemisorption was lower for both low molecular weight molecules and decyltrimethoxysilane (D) with a high molecular weight. For fluorocarbon chains, the amount of chemisorption was lower for low molecular weight molecules, whereas it increased significantly by heating for high molecular weight type of 1H,1H,2H,2H‐heptadecafluorodecyltriethoxysilane (F). Wide‐angle X‐ray diffraction analysis of F‐treated silica particles showed that the fluorocarbon chains formed an ordered structure. There was no such indication for the D‐treated system. This ordered structure seems to influence on higher chemisorption for F‐treated systems.
Follow‐up spectroscopy of comet C/2020 F3 (NEOWISE)
Authors: Bischoff Richard , Mugrauer Markus
Published: June 2021

We present spectroscopy of the coma center of comet C/2020 F3 (NEOWISE), carried out at the end of July 2020 with the Échelle spectrograph FLECHAS at the University Observatory Jena. The comet was observed in five nights and many prominent emission features were detected between 4,685 and 7,376 Å. Beside the C2 Swan emission bands also several emission features of the amidogen radical, as well as two forbidden lines of oxygen were identified in the FLECHAS spectra of the comet in all observing epochs. In contrast, strong sodium emission was detected only in the spectra of the comet, taken on 21 and July 23, 2020, which significantly faded between these two nights, and was no longer present in the spectra as of July 29, 2020. In this paper, we present and characterize the most prominent emission features, detected in the FLECHAS spectra of the comet, discuss their variability throughout our spectroscopic monitoring campaign, and use them to derive the radial velocity of the comet in all observing nights.
Telomere shortening in late‐life depression: A potential marker of depression severity
Authors: Mendes‐Silva Ana Paula , Vieira Erica Leandro Marciano , Xavier Gabriela , Barroso Lucelia Scarabeli Silva , Bertola Laiss , Martins Efrem Augusto Ribeiro , Brietzke Elisa Macedo , Belangero Sintia Iole Nogueira , Diniz Breno Satler
Published: June 2021

Objectives

Telomeres are structures at the extremity of chromosomes that prevents genomic instability, and its shortening seems to be a hallmark of cellular aging. Past studies have shown contradictory results of telomere length (TL) in major depression, and are a few studies in late‐life depression (LLD). This explores the association between TL as a molecular marker of aging and diagnosis of LLD, the severity of depressive symptoms, and cognitive performance in older adults.

Methods/design

We included 78 older adults (45 with LLD and 33 nondepressed controls, according to DSM‐V criteria), aged 60–90 years. TL was measured in leukocytes by a quantitative polymerase chain reaction, determining the relative ratio (T/S) between the telomere region copy number (T) and a single copy gene (S), using a relative standard curve.

Results

TL was significantly shorter in the LLD compared with control participants (p = .039). Comparing groups through the severity of depressive symptoms, we found a negative correlation with the severity of depressive symptoms (Hamilton Depression Rating Scale‐21, r = −0.325, p = .004) and medical burden (r = −0.271, p = .038). There was no significant correlation between TL and cognitive performance (Mattis Dementia Rating Scale, r = 0.152, p = .21).

Conclusions

We found that older adults with LLD have shorter telomere than healthy controls, especially those with a more severe depressive episode. Our findings suggest that shorter TL can be a marker of the severity of depressive episodes in older adults and indicate that these individuals may be at higher risk of age‐associated adverse outcomes linked to depression.
Pro12Ala polymorphism of peroxisome proliferator activated receptor gamma 2 may be associated with adverse neurodevelopment in European preterm babies
Authors: Victor Suresh , Chew Andrew , Falconer Shona
Published: June 2021

Introduction

Prematurity is the leading cause of death and disability in children under 5 years of age. Understanding the molecular mechanisms of the biological processes involved in preterm brain injury may help develop novel neuroprotective treatment strategies. A growing body of evidence suggest that peroxisome proliferator‐activated receptor gamma (PPARγ) signaling is associated with inhibited brain development in preterm babies. The Ala allele of the Pro12Ala polymorphism of PPARγ2 decreases receptor binding affinity and consequently induces a reduction of PPARγ signaling.

Methods

In this study, we carried out a preliminary analysis of existing datasets to test the hypothesis that reduced transactivation capacity of PPARγ in the presence of the Ala variant of PPARγ2 may be associated with adverse neurodevelopment in preterm babies.

The association between PPAR‐γ2 Pro12Ala polymorphism and neurodevelopment at 18–24 months of age was assessed in two groups of European infants, 155 born before 33 weeks’ gestation and 180 born later than 36 weeks’ gestation using a linear regression model. The Bayley Scales of Infant and Toddler Development–3rd edition was administered to assess neurodevelopment at 18–24 months of age.

Results

We observed the Ala allele of the Pro12Ala polymorphism in 25% preterm infants and 20% term infants. The Ala allele of PPARγ2 was significantly associated with adverse cognitive (p = .019), language (p = .03), and motor development (p = 0.036) at 18–24 months of age after taking into consideration the duration of ventilation, gender, and index of multiple deprivation scores, but without correction for potential shared ancestry. There was no association between the PPAR‐γ2 Pro12Ala polymorphism and neurodevelopment in term infants.

Conclusions

These preliminary data suggest that PPARγ signaling in the presence of the Ala variant of PPARγ2 may be associated with adverse neurodevelopment in preterm infants suggesting that further studies are warranted.
Comparative Nucleosomal Reactivity of 5‐Formyl‐Uridine and 5‐Formyl‐Cytidine
Authors: Runtsch Leander Simon , Stadlmeier Michael , Schön Alexander , Müller Markus , Carell Thomas
Published: June 2021

5‐Formyl‐deoxyuridine (fdU) and 5‐formyl‐deoxycytidine (fdC) are formyl‐containing nucleosides that are created by oxidative stress in differentiated cells. While fdU is almost exclusively an oxidative stress lesion formed from deoxythymidine (T), the situation for fdC is more complex. Next to formation as an oxidative lesion, it is particularly abundant in stem cells, where it is more frequently formed in an epigenetically important oxidation reaction performed by α‐ketoglutarate dependent TET enzymes from 5‐methyl‐deoxycytidine (mdC). Recently, it was shown that genomic fdC and fdU can react with the ϵ‐aminogroups of nucleosomal lysines to give Schiff base adducts that covalently link nucleosomes to genomic DNA. Here, we show that fdU features a significantly higher reactivity towards lysine side chains compared with fdC. This result shows that depending on the amounts of fdC and fdU, oxidative stress may have a bigger impact on nucleosome binding than epigenetics.
A retrospective analysis of discharge summaries from a tertiary care hospital medical oncology unit: To assess compliance with documentation of recommended discharge summary components
Authors: Ge Jingwei , Davis Alison , Jain Ankit
Published: June 2021

Background

Discharge summaries are essential for health transition between inpatient hospital teams and outpatient general practices. The patient's outcome is dependent on the quality and timeliness of discharge summaries.

Aim

A retrospective analysis was carried out to assess the compliance with recommended documentation of 697 electronic discharge summaries (eDSs) of oncology inpatients discharged in 2018 from the Canberra Hospital according to the National Guidelines of On‐Screen Presentation of Discharge Summaries.

Methods and results

Individual medical records were identified and screened for the recommended eDS components according to the National Guidelines. Out of the 17 recommended components, nine components were included in all discharge summaries, two components in more than 99% and two components in 95–96% of discharge summaries. The most frequently omitted components include “information provided to the patient,” “ceased medicine” and “procedures,” and these were omitted in 8, 38 and 82% of discharge summaries, respectively.

Conclusion

Overall, most discharge summaries adhered to the national guidelines quite well by including most of the recommended components. However, the discharge summary quality is still inadequate in some domains.
Genome‐Wide Approach to Measure Variant‐Based Heritability of Drug Outcome Phenotypes
Authors: Muhammad Ayesha , Aka Ida T. , Birdwell Kelly A. , Gordon Adam S. , Roden Dan M. , Wei Wei‐Qi , Mosley Jonathan D. , Van Driest Sara L.
Published: June 2021

Pharmacogenomic studies have successfully identified variants—typically with large effect sizes in drug target and metabolism enzymes—that predict drug outcome phenotypes. However, these variants may account for a limited proportion of phenotype variability attributable to the genome. Using genome‐wide common variation, we measured the narrow‐sense heritability () of seven pharmacodynamic and five pharmacokinetic phenotypes across three cardiovascular drugs, two antibiotics, and three immunosuppressants. We used a Bayesian hierarchical mixed model, BayesR, to model the distribution of genome‐wide variant effect sizes for each drug phenotype as a mixture of four normal distributions of fixed variance (0, 0.01%, 0.1%, and 1% of the total additive genetic variance). This model allowed us to parse into bins representing contributions of no‐effect, small‐effect, moderate‐effect, and large‐effect variants, respectively. For the 12 phenotypes, a median of 969 (range 235–6,304) unique individuals of European ancestry and a median of 1,201,626 (range 777,427–1,514,275) variants were included in our analyses. The number of variants contributing to ranged from 2,791 to 5,356 (median 3,347). Estimates for ranged from 0.05 (angiotensin‐converting enzyme inhibitor–induced cough) to 0.59 (gentamicin concentration). Small‐effect and moderate‐effect variants contributed a majority to for every phenotype (range 61–95%). We conclude that drug outcome phenotypes are highly polygenic. Thus, larger genome‐wide association studies of drug phenotypes are needed both to discover novel variants and to determine how genome‐wide approaches may improve clinical prediction of drug outcomes.
Culture of Rat Primary Cortical Cells for Microelectrode Array (MEA) Recordings to Screen for Acute and Developmental Neurotoxicity
Authors: Gerber Lora‐Sophie , van Melis Lennart V.J. , van Kleef Regina G.D.M. , de Groot Aart , Westerink Remco H.S.
Published: June 2021

Neurotoxicity testing of chemicals, drug candidates, and environmental pollutants still relies on extensive in vivo studies that are very costly, time‐consuming, and ethically debated due to the large number of animals typically used. Currently, rat primary cortical cultures are widely used for in vitro neurotoxicity studies, as they closely resemble the in vitro brain with respect to the diversity of cell types, their physiological functions, and the pathological processes that they undergo. Common in vitro assays for neurotoxicity screening often focus on very target‐specific endpoints such as morphological, biochemical, or electrophysiological changes, and such narrow focus can hamper translation and interpretation. Microelectrode array (MEA) recordings provide a non‐invasive platform for extracellular recording of electrical activity of cultured neuronal cells, thereby enabling the evaluation of changes in neuronal (network) function as a sensitive and integrated endpoint for neurotoxicity screening. Here, we describe an in vitro approach for assessing changes in neuronal network function as a measure for neurotoxicity, using rat primary cortical cultures grown on MEAs. We provide a detailed protocol for the culture of rat primary cortical cells, and describe several experimental procedures to address acute, subchronic, and chronic exposure scenarios. We additionally describe the steps for processing and analyzing MEA and cell viability data. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Isolation and culture of rat primary cortical cells on 48‐well MEA plates

Support Protocol 1: Pretreatment and washing of 48‐well MEA plates before first use or for re‐use

Support Protocol 2: Coating of 48‐well MEA plates with 0.1% PEI solution

Basic Protocol 2: MEA measurements during acute exposure

Alternate Protocol 1: MEA measurements during subchronic exposure

Alternate Protocol 2: MEA measurements during chronic exposure

Support Protocol 3: Determination of cell viability after MEA experiments

Basic Protocol 3: MEA data processing

Basic Protocol 4: Analyzing MEA experiments after acute and subchronic exposure

Alternate Protocol 3: Analyzing MEA experiments after chronic exposure
Reconfigurable field‐programmable gate array‐based on‐chip learning neuromorphic digital implementation for nonlinear function approximation
Authors: Gholami Morteza , Zaman Farsa Edris , Karimi Gholamreza
Published: June 2021

Hardware implementations of spiking neural networks, which are known as neuromorphic architectures, provide an explicit understanding of brain performance. As a result, biological features of the brain may well inspire the next generation of computers and electronic systems used in such areas as signal processing, image processing, function approximation, and pattern recognition. Approximating nonlinear functions has many uses in computer science and applied mathematics. The sigmoid is the most universal activation function in neural networks by which the relationship between biological and artificial neurons is defined. It is a suitable option for predicting the probability of anything from 0 to 1 as output. In this paper, a spiking neural network using Izhikevich neurons and a gradient descent learning algorithm are propounded to approximate the sigmoid and other nonlinear functions. The flexibility of the spiking network is demonstrated by showing the average relative errors in the approximation process. A time‐ and cost‐efficient digital neuromorphic implementation on the base of on‐chip learning method for approximating the sigmoid function is also discussed. The paper reports the results of the hardware synthesis and the spiking network's physical implementation on a field‐programmable gate array. The maximum frequency and throughput of the implemented network were 83.209 MHz and 9.86 Mb/s, respectively.
An active parallel power decoupling circuit with a dual loop control scheme for micro‐inverters
Authors: Rezaei Mohammad Hossein , Akhbari Mahdi
Published: June 2021

An important challenge in single‐stage single‐phase micro‐inverters is reducing required capacitance by various active power decoupling (APD) techniques in order to use film capacitors with a longer lifetime instead of electrolytic capacitors. In this paper, a photovoltaic (PV)‐side parallel APD circuit based on a bidirectional flyback converter is proposed. This topology is able to increase the average and ripple voltages for the capacitor due to having a transformer and thus can reduce the required capacitance. In the control scheme, dual control loops on the main and decoupling circuits manage the micro‐inverter operation. The primary control loop is based on the instantaneous active and reactive power theory and a proportional resonant (PR) controller that is responsible for delivering the PV panel energy to the grid. The secondary control loop regulates the pulsation power on the dc‐link capacitor through the PR controller. Simulation results demonstrated that the proposed APD circuit and the control method could properly damp the pulsation power in the normal and reference tracking operations. Furthermore, the good robustness of the micro‐inverter was confirmed in shutdown and start‐up. Finally, the experimental results with a 180‐W single‐phase micro‐inverter prototype are presented, which validates the advantages of the proposed configuration.
Synthesis and evaluation of 2‐(4‐[4‐acetylpiperazine‐1‐carbonyl] phenyl)‐1H‐benzo[d]imidazole‐4‐carboxamide derivatives as potential PARP‐1 inhibitors and preliminary study on structure‐activity relationship
Authors: Chen Miaojia , Huang Honglin , Wu Kaiyue , Liu Yunfan , Jiang Lizhi , Li Yang , Tang Guotao , Peng Junmei , Cao Xuan
Published: June 2021

Although 1H‐benzo[d]imidazole‐4‐carboxamide derivatives have been explored for a long time, the structure–activity relationship of the substituents in the hydrophobic pocket (AD binding sites) has not thoroughly discovered. Here in, a series of 2‐(4‐[4‐acetylpiperazine‐1‐carbonyl]phenyl)‐1H‐benzo[d]imidazole‐4‐carboxamide derivatives have been designed, synthesized, and successful characterization as novel and effective poly ADP‐ribose polymerases (PARP)‐1 inhibitors to improve the structure–activity relationships about the substituents in the hydrophobic pocket. These derivatives were evaluated for their PARP‐1 inhibitory activity and cellular inhibitory against BRCA‐1 deficient cells (MDA‐MB‐436) and wild cells (MCF‐7) using PARP kit assay and MTT method. The results indicated that compared with other heterocyclic compounds, furan ring‐substituted derivatives 14n‐14q showed better PARP‐1 inhibitory activity. Among this derivatives, compound 14p displayed the strongest inhibitory effects on PARP‐1 enzyme (IC50 = 0.023 μM), which was close to that of Olaparib. 14p (IC50 = 43.56 ± 0.69 μM) and 14q (IC50 = 36.69 ± 0.83 μM) displayed good antiproliferation activity on MDA‐MB‐436 cells and inactivity on MCF‐7 cells, indicating that 14p and 14q have high selectivity and targeting. The molecular docking method was used to explore the binding mode of compound 14p and PARP‐1, and implied that the formation of hydrogen bond was essential for PARP‐1 inhibition activities. This study also showed that in the hydrophobic pocket (AD binding sites), the introduction of strong electronegative groups (furan ring, e.g.) or halogen atoms in the side chain of benzimidazole might improve its inhibitory activity and this strategy could be applied in further research.
Cooperation and opportunism in Galapagos sea lion hunting for shoaling fish
Authors: De Roy Tui , Espinoza Eduardo R. , Trillmich Fritz
Published: June 2021

For predators, cooperation can decrease the cost of hunting and potentially augment the benefits. It can also make prey accessible that a single predator could not catch. The degree of cooperation varies substantially and may range from common attraction to a productive food source to true cooperation involving communication and complementary action by the individuals involved. We here describe cooperative hunting of Galapagos sea lions (Zalophus wollebaeki) for Amberstripe scad (Decapterus muroadsi), a schooling, fast swimming semipelagic fish. A group of 6–10 sea lions, usually females only, drove scad over at least 600–800 m from open water into a cove where, in successful hunts, they drove them ashore. Frequently, these “core hunters” were joined toward the final stages of the hunt by another set of opportunistic sea lions from a local colony at that beach. The “core hunters” did not belong to that colony and apparently were together coming toward the area specifically for the scad hunt. Based on the observation of 40 such hunts from 2016 to 2020, it became evident that the females performed complementary actions in driving the scad toward the cove. No specialization of roles in the hunt was observed. All “core hunters” and also opportunistically joining sea lions from the cove shared the scad by randomly picking up a few of the 25–300 (mean 100) stranded fish as did scrounging brown pelicans. In one of these hunts, four individual sea lions were observed to consume 7–8 fish each in 25 s. We conclude that the core hunters must communicate about a goal that is not present to achieve joint hunting but presently cannot say how they do so. This is a surprising achievement for a species that usually hunts singly and in which joint hunting plays no known role in the evolution of its sociality.
Water depth influences algal distribution and productivity in shallow agricultural lakes
Authors: Henderson Kate A. , Murdock Justin N. , Lizotte Richard E.
Published: June 2021

Agricultural activity can alter water quality and quantity resulting in lakes facing increasing interactive stressors including eutrophication, suspended sediment and water withdrawal. This study examined the relationships between water depth, water quality and algae in shallow agricultural lakes in the lower Mississippi River Basin (LMRB) to assess how lake depth influences algal structure and function, focusing on factors that typically regulate growth, that is, light, temperature and nutrients. Lake water and sediment cores were collected in shallow (mean = 0.8 m) and deep (mean = 1.7 m) locations in three lakes seasonally for 1 year. Additionally, interactive effects of light and temperature on algal growth were investigated through a laboratory experiment to determine the relative importance of each in regulating algal biomass and net oxygen production. In these shallow, turbid, eutrophic lakes, deeper water had lower nutrient concentrations and temperature across all seasons and clearer water in the summer. Shallow areas had more phytoplankton and periphyton. Water temperature had a stronger correlation than light with both phytoplankton and periphyton biomass. Algal biomass generally decreased with increasing water temperature, but biomass was better predicted by increasing nitrogen availability, and productivity declined with greater phosphorus availability. Water depth was therefore likely influencing different locations of the same lake towards different algal stable states. Mitigating excess algal production is an important goal towards limiting hypoxic conditions in the LMRB, and increasing water storage could help moderate temperature, nutrients and turbidity effects that contribute to algal blooms in lakes receiving agricultural runoff.
Ligand Effects in Carbon−Boron Coupling Processes Mediated by σ‐BH Platinum Complexes
Authors: Ríos Pablo , Fernández‐de‐Córdova Francisco José , Borge Javier , Curado Natalia , Lledós Agustí , Conejero Salvador
Published: June 2021

The reaction of tri‐coordinated boranes (derived from dioxaborolanes and diazaborolanes) with cyclometalated low‐electron count platinum complexes [Pt(NHC’)(NHC)][BArF] (NHC=ItBuiPr, IMes, IMes*) led, at low temperature, to the formation of the corresponding σ‐BH species. Some of these species have been characterized by X‐Ray diffraction methods showing a rare η1‐coordination mode. These compounds are thermally unstable and undergo a carbon‐boron coupling process whose reversibility depends on the NHC ligand. DFT calculations indicate that the energy barriers required for C−B bond formation events (together with Pt−H bonds) are lower than the competitive reactions leading to C−H bond formation (and Pt−B bonds). However, the C−B coupling products appear to be formed under kinetic control with ItBuiPr ligands, whereas the relative low energy barrier leading to C−H bond formation is sufficiently low to form the thermodynamically more stable platinum boryl complexes at rt. The latter energy barrier is, nevertheless, too high for the systems bearing IMes and IMes* ligands.
Comparison of two storage units for a sustainable off‐grid climate refuge shelter
Authors: Niaz Fariha , AlShafi Manal , Bicer Yusuf
Published: June 2021

Considering the broad range of applications, efficient retrieval and storing electrical energy methods are still challenging. Besides the load variations, the ever‐increasing intermittent renewable energy penetration into the grid system has witnessed the system complexities. In off‐grid applications, energy storage can balance electricity consumption and electricity generation to avoid voltage and frequency deviations. This research paper focuses on the energy management of an off‐grid climate refuge system used for hot and arid locations with a system comparison for two routes of different storage techniques, namely flywheels and a lithium‐ion battery. The proposed system can generate its power from photovoltaics and provide cooling and other auxiliaries through vapor compression cycle and water misting units with an operation of about 16 hours (ie, from 7:00 am to 11:00 pm) on the weekdays and 12 hours on the weekends. A comparison of levelized costs is conducted for the evaluation using HOMER software. The annual energy production by solar photovoltaics for the proposed system is 20 MWh, and the annual consumption is 16 MWh. The photovoltaic‐battery storage system has shown the lowest cost of electricity, corresponding to 0.761 $/kWh, and net present cost of $66 238 and is optimum in all sensitivity analysis cases.
Assessing the effects of inulin‐type fructan intake on body weight, blood glucose, and lipid profile: A systematic review and meta‐analysis of randomized controlled trials
Authors: Li Liangkui , Li Peng , Xu Li
Published: June 2021

Inulin‐type fructan (ITF) intake has been suggested to alleviate several features of metabolic syndrome including obesity, diabetes, and hyperlipidemia; yet, results from the human trials remained inconsistent. We aimed to systematically evaluate the effects of ITF intake on body weight, glucose homeostasis, and lipid profile on human subjects with different health status, including healthy, overweight and obese, prediabetes and diabetes, and hyperlipidemia. Weighted mean differences (WMDs) between ITF and control groups were calculated by a random‐effects model. A total of 33 randomized controlled human trials were included. Significant effect of ITF intake was only observed in the diabetics, but not in the other subject groups. Specifically, ITF intervention significantly decreased the WMD of blood glucose (−0.42 mmol/L; 95% CI: −0.71, −0.14; p = .004), total cholesterol (−0.46 mmol/L; 95% CI: −0.75, −0.17; p = .002), and triglycerides (TAG) (−0.21 mmol/L; 95% CI: −0.37, −0.05; p = .01) compared with the control. The stability of these favorable effects of ITF on diabetics was confirmed by sensitivity analysis. Also, ITF tends to lower LDL cholesterol (p = .084). But body weight and blood insulin were not affected by ITF intake. It should be noted that blood glucose, total cholesterol, and LDL cholesterol exhibited high unexplained heterogeneity. In conclusion, ITF intake lowers blood glucose, total cholesterol, and TAG in the people with diabetes, and they may benefit from addition of inulin into their diets, but the underlying mechanisms responsible for these effects are inconclusive.
Implications of measurement metrics on soil freezing curves: A simulation of freeze–thaw hysteresis
Authors: Pardo Lara Renato , Berg Aaron A. , Warland Jon , Parkin Gary
Published: June 2021

Soil freeze–thaw events have important implications for water resources, flood risk, land productivity, and climate change. A property of these phenomena is the relationship between unfrozen water content and sub‐freezing temperature, known as the soil freezing characteristic curve (SFC). It is documented that this relationship exhibits hysteretic behaviour when frozen soil thaws, leading to the definition of the soil thawing characteristic curve (STC). Although explanations have been given for SFC/STC hysteresis, the effect that ‘scale’ – particularly ‘measurement scale’ – may have on these curves has received little attention. The most commonly used measurement scale metric is the ‘support’, which is the spatial (or temporal) unit within which the measured variable is integrated or soil volume sampled. We show (a) measurement support can influence the range and shape of the SFC and (b) hysteresis can be attributed, in part, to the support and location of the measurements comprising the SFC/STC. We simulated lab measured temperature, volumetric water content (VWC), and permittivity from soil samples undergoing freeze–thaw transitions using Hydrus‐1D and a modified Dobson permittivity model. To assess the effect of measurement support and location on SFC/STC, we masked the simulated temperature and VWC/permittivity extent to match the instrument's support and location. By creating a detailed simulation of the intra‐ and inter‐support variability associated with the penetration of a freezing front, we demonstrate how measurement support and location can influence the temperature range over which water freezing events are captured. We show it is possible to simulate hysteresis in homogenous media with purely geometric considerations, suggesting that SFC/STC hysteresis may be more of an apparent phenomenon than mechanistically real. Lastly, we develop an understanding of how the location and support of soil temperature and VWC/permittivity measurements influence the temperature range over which water freezing events are captured.