bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of 7SK snRNA Mimics That Inhibit HIV Transcription
Authors: Yamayoshi Asako , Fukumoto Hiroyuki , Hayashi Rie , Kishimoto Kyosuke , Kobori Akio , Koyanagi Yoshio , Komano Jun A. , Murakami Akira
Published: July 2021

The 332‐nucleotide small nuclear RNA (snRNA) 7SK is a highly conserved non‐coding RNA that regulates transcriptional elongation. By binding with positive transcriptional elongation factor b (P‐TEFb) via HEXIM1, 7SK snRNA decreases the kinase activity of P‐TEFb and inhibits transcriptional elongation. Additionally, it is reported that 7SK inhibition results in the stimulation of human immunodeficiency virus (HIV)‐specific transcription. These reports suggest that 7SK is a naturally occurring functional molecule as negative regulator of P‐TEFb and HIV transcription. In this study, we developed functional oligonucleotides that mimic the function of 7SK (7SK mimics) as novel inhibitors of HIV replication. We defined the essential region of 7SK regarding its suppressive effects on transcriptional downregulation using an antisense strategy. Based on the results, we designed 7SK mimics containing the defined region. The inhibitory effects of 7SK mimics on HIV‐1 long terminal repeat promoter specific transcription was drastic compared with those of the control mimic molecule. Notably, these effects were found to be more enhanced by co‐transfection with Tat‐expressing plasmids. From these results, it is indicated that 7SK mimics may have great therapeutic potential for HIV/AIDS treatment.
The role of geographic distance from a cancer center in survival and stage of AYA cancer diagnoses
Authors: Darlington Wendy S. , Green Adam L.
Published: July 2021

In this editorial, the authors examine the current understanding of geographic differences affecting outcomes for adolescent and young adult patients with cancer and explore future directions to potentially mitigate these effects.
Generation of Single‐Chain Variable Fragment (scFv) Libraries for Use in Phage Display
Authors: Schladetsch Megan A. , Wiemer Andrew J.
Published: July 2021

Phage display is a powerful platform for the discovery of novel biologics with high binding affinities to a specific target protein. Here, we describe methods to construct a phage display library containing diverse single‐chain variable antibody fragments (scFvs). Specifically, updated methods for polymerase chain reaction (PCR) amplification and fusion of human antibody genes, their ligation into the pComb3X vector for transformation into 5αF′Iq competent bacterial cells, and their expression in M13KO7 helper phage are presented. Additionally, we describe how to amplify and quantify the phage library and to prepare it in various formats for short‐ and long‐term storage. © 2021 Wiley Periodicals LLC.

Basic Protocol 1: First‐round polymerase chain reaction (PCR) for isolation of antibody fragments

Basic Protocol 2: Ethanol precipitation and pooling of fragment DNA

Basic Protocol 3: Second‐round polymerase chain reaction with splicing by overlap extension (SOE) for antibody fragment fusion

Basic Protocol 4: Restriction digestion of individual scFv constructs and pComb3XSS vector

Basic Protocol 5: Directional ligation of the scFv constructs and pComb3X backbone

Basic Protocol 6: Transformation of pComb‐scFv plasmids into 5αF′Iq competent cells

Basic Protocol 7: Collection of bacteria containing the scFv library

Basic Protocol 8: Preparation of bacterial glycerol stock

Basic Protocol 9: Preparation of phage library glycerol stock

Basic Protocol 10: Preparation of plasmid DNA stock

Basic Protocol 11: Amplification of M13KO7 helper phage

Basic Protocol 12: Phage titer by plate assay

Alternate Protocol: One‐plate phage plaque assay
Onion (Allium cepa L.) hybrid seed production: Sugar content variation during the flowering period
Authors: Soto Verónica Carolina , Gatica Ismael Jairo Gabriel , Galmarini Claudio Rómulo
Published: July 2021

Honeybees (Apis mellifera L.) are the most used pollinators for onion (Allium cepa L.) seed production. Two types of onion varieties are mainly grown worldwide: hybrids and open pollination (OP) cultivars. Although hybrids offer advantages to bulb growers, seed yields of hybrids are lower than OP cultivars. Since honeybees play a major role in onion pollination, understanding the contribution of the floral rewards to bee visitation is crucial to improve seed yield. The goal of this study is to establish the best moment for the introduction of honeybee hives into onion fields to increase seed yields. To reach this goal, the correlation between sugar compounds in nectar throughout the flowering period and honeybee foraging activity was determined. The sugar profile and bee visits were highly correlated, and fructose concentration was strongly linked to bee frequency of foraging on the onion umbels. The highest number of bee visits was recorded at 70% of flowering. Based on these results, beehives should be introduced once 40–50% of flowering is reached.
Extracellular matrix and Hippo signaling as therapeutic targets of antifibrotic compounds for uterine fibroids
Authors: Islam Md Soriful , Afrin Sadia , Singh Bhuchitra , Jayes Friederike L. , Brennan Joshua T. , Borahay Mostafa A. , Leppert Phyllis C. , Segars James H.
Published: July 2021

Background

Uterine fibroids are highly prevalent, collagen‐rich, mechanically stiff, fibrotic tumors for which new therapeutic options are needed. Increased extracellular matrix (ECM) stiffness activates mechanical signaling and Hippo/YAP promoting fibroid growth, but no prior studies have tested either as a therapeutic target. We tested the hypothesis that injection of a purified form of collagenase Clostridium histolyticum (CCH) that selectively digests type I and type III collagens would alter ECM stiffness, Hippo signaling, and selectively reduce fibroid cell growth. We also used two FDA‐approved drugs, verteporfin and nintedanib, to elucidate the role of Hippo/YAP signaling in uterine fibroid and myometrial cells.

Methods

The clinical trial was registered (NCT02889848). Stiffness of samples was measured by rheometry. Protein expression in surgical samples was analyzed via immunofluorescence. Protein and gene expression in uterine fibroid or myometrial cell lines were measured by real time PCR and western blot, and immunofluorescence.

Results

Injection of CCH at high doses (0.1–0.2 mg/cm3) into fibroids resulted in a 46% reduction in stiffness in injected fibroids compared to controls after 60 days. Levels of the cell proliferation marker proliferative cell nuclear antigen (PCNA) were decreased in fibroids 60 days after injection at high doses of CCH. Key Hippo signaling factors, specifically the transcriptionally inactive phosphorylated YAP (p‐YAP), was increased at high CCH doses, supporting the role of YAP in fibroid growth. Furthermore, inhibition of YAP via verteporfin (YAP inhibitor) decreased cell proliferation, gene and protein expression of key factors promoting fibrosis and mechanotransduction in fibroid cells. Additionally, the anti‐fibrotic drug, nintedanib, inhibited YAP and showed anti‐fibrotic effects.

Conclusions

This is the first report that in vivo injection of collagenase into uterine fibroids led to a reduction in Hippo/YAP signaling and crucial genes and pathways involved in fibroid growth. These results indicate that targeting ECM stiffness and Hippo signaling might be an effective strategy for uterine fibroids.
Detection criteria and post‐field sample processing influence results and cost efficiency of occupancy‐based monitoring
Authors: Lonsinger Robert C. , Knight Robert N. , Waits Lisette P.
Published: July 2021

Optimization of occupancy‐based monitoring has focused on balancing the number of sites and surveys to minimize field efforts and costs. When survey techniques require post‐field processing of samples to confirm species detections, there may be opportunities to further improve efficiency. We used scat‐based noninvasive genetic sampling for kit foxes (Vulpes macrotis) in Utah, USA, as a model system to assess post‐field data processing strategies, evaluate the impacts of these strategies on estimates of occupancy and associations between parameters and predictors, and identify the most cost‐effective approach. We identified scats with three criteria that varied in costs and reliability: (1) field‐based identification (expert opinion), (2) statistical‐based morphological identification, and (3) genetic‐based identification (mitochondrial DNA). We also considered four novel post‐field sample processing strategies that integrated statistical and genetic identifications to reduce costly genetic procedures, including (4) a combined statistical‐genetic identification, (5) a genetic removal design, (6) a within‐survey conditional‐replicate design, and (7) a single‐genetic‐replicate with false‐positive modeling design. We considered results based on genetic identification as the best approximation of truth and used this to evaluate the performance of alternatives. Field‐based and statistical‐based criteria prone to misidentification produced estimates of occupancy that were biased high (˜1.8 and 2.1 times higher than estimates without misidentifications, respectively). These criteria failed to recover associations between parameters and predictors consistent with genetic identification. The genetic removal design performed poorly, with limited detections leading to estimates that were biased high with poor precision and patterns inconsistent with genetic identification. Both statistical‐genetic identification and the conditional‐replicate design produced occupancy estimates comparable to genetic identification, while recovering the same model structure and associations at cost reductions of 67% and 74%, respectively. The false‐positive design had the lowest cost (88% reduction) and recovered patterns consistent with genetic identification but had occupancy estimates that were ˜32% lower than estimated occupancy based on genetic identification. Our results demonstrate that careful consideration of detection criteria and post‐field data processing can reduce costs without significantly altering resulting inferences. Combined with earlier guidance on sampling designs for occupancy modeling, these findings can aid managers in optimizing occupancy‐based monitoring.
Core and occasional species: A new way forward
Authors: Helden Alvin J.
Published: July 2021

Various methods have been used to divide communities into core species and occasional or satellite species. Some methods are somewhat arbitrary, and there is evidence that many communities are more multimodal than bimodal. They also tend to rely on having multiple years of data.

A completely novel method is presented that not only has no requirement for long‐term datasets but can divide communities into multiple groups. It is based on probability a species is present, calculated using Simpson's index and the sequential removal of species from the data.

The sequential Simpson's index method was applied to species data from a grassland insect community. It was also applied to eleven other datasets that had been divided into core and occasional species in previously published studies.

The new method was found not only to be consistent with previous core–occasional assessments but also able to identify multimodality in species abundance distributions.

Although ideally used with a measure of persistence (frequency of occurrence) to rank species, community structure is consistently described even with only species abundance data.

The method can be applied to short or long‐term datasets and can help identify multimodality and provide valuable insight into how communities change in time or space.
Building the Stable Oxygen Framework in High‐Ni Layered Oxide Cathode for High‐Energy‐Density Li‐Ion Batteries
Authors: Wang Yang‐Yang , Wang Yu‐Yang , Liu Sheng , Li Guo‐Ran , Zhou Zhen , Xu Ning , Wu Meng‐Tao , Gao Xue‐Ping
Published: July 2021

High‐Ni layered oxide cathodes hold a great promise for fabricating high‐energy lithium‐ion batteries. However, the oxygen evolution during cycling is a crucial factor in the structure deterioration, potential change, and capacity decay of cathodes, limiting the commercial application of high‐Ni (Ni > 0.9) layered oxides in batteries. Herein, we demonstrate a feasible approach to enhance the stability of oxygen framework, through the surface oxygen immobilization with yttrium and bulk oxygen stabilization with aluminum in high‐Ni layered oxides. As expected, benefiting from the oxygen‐stabilized framework, the bulk structure deterioration, and interfacial parasitic reaction are mitigated obviously during battery operation, along with the improved thermal stability of cathode. Correspondingly, the as‐prepared high‐Ni oxide delivers high reversible capacity, impressive cycle ability, and low potential polarization upon cycling. Such significant improvement on the electrochemical performance is primarily attributed to the strong oxygen affinities of both yttrium at the surface layer and aluminum in the bulk, which synergistically stabilizes the oxygen framework of high‐Ni oxide via raising the energy barrier for oxygen evolution. Therefore, building the stable oxygen framework is critical for enhancing the energy density output, cycle operation, and thermal stability of high‐Ni oxide cathodes.
The effect of infertile semen on the mRNA‐based body fluid identification
Authors: Tian Huan , Huang Sicheng , Bai Peng , Xiao Xiao , Peng Duo , Zhao Huan , Liu Yuqing , Feng Qian , Liao Miao , Li Fuping , Liang Weibo
Published: July 2021

In the past decade, mRNA markers have been well demonstrated as promising molecular markers in forensic body fluid identification (BFI), and successfully used in wide applications. Several studies have assessed the performance of semen‐specific mRNA markers in distinguishing semen from other common body fluids at the crime scene. Infertility has been reported as a global health problem that is affecting approximately 15% of couples worldwide. Therefore, it is important for forensic researchers to consider the impact of infertility on semen identification. This study aimed to explore the effect of semen from infertile men (hereinafter “infertile semen”) on BFI and to identify semen‐specific mRNAs that can efficiently and accurately distinguish normal and infertile semen samples from other body fluids. Results showed that the selected five mRNAs (KLK3, TGM4, SEMG1, PRM1, and PRM2) performed a significantly high semen specificity in normal semen. Moreover, KLK3 was slightly influenced by infertile semen samples with over 98% positive results in all semen samples. The accuracy to predict normal semen reached up to 96.6% using the discrimination function Y1 with KLK3 and PRM1. However, when the infertile semen samples were included in discrimination function (function Y2 with KLK3), the accuracy rate of semen identification (including the normal and infertile semen) was down to 89.5%. Besides, the sensitivity of multiplex assay could reach down to 50pg. Our results suggest that it is important to consider the presence of infertile semen when using mRNAs to identify semen samples, which would have a far‐reaching impact in forensic identification.
Approximate analytic expressions for the diffusiophoretic velocity of a spherical colloidal particle
Authors: Ohshima Hiroyuki
Published: July 2021

The general expression is derived for the diffusiophoretic velocity of a spherical colloidal particle of radius a in a concentration gradient of symmetrical electrolyte. On the basis of this expression, simple approximate analytic expressions for the diffusiophoretic velocity correct up to the order of 1/κa is derived, where κ is the Debye‐Hückel parameter. It is found that the approximate expression correct to order unity can be applied for κa ≥ 50 with negligible errors, while the approximate expression correct to order 1/κa can be applied for κa ≥ 20 with negligible errors.
Fatty Acid Synthase–Suppressor Screening Identifies Sorting Nexin 8 as a Therapeutic Target for NAFLD
Authors: Hu Yufeng , He Wenzhi , Huang Yongping , Xiang Hui , Guo Juan , Che Yan , Cheng Xu , Hu Fengjiao , Hu Manli , Ma Tengfei , Yu Jie , Tian Han , Tian Song , Ji Yan‐Xiao , Zhang Peng , She Zhi‐Gang , Zhang Xiao‐Jing , Huang Zan , Yang Juan , Li Hongliang
Published: July 2021

Background and Aims

NAFLD is the most prevalent chronic liver disease without any Food and Drug Administration–approved pharmacological intervention in clinic. Fatty acid synthase (FASN) is one of the most attractive targets for NAFLD treatment because of its robust rate‐limiting capacity to control hepatic de novo lipogenesis. However, the regulatory mechanisms of FASN in NAFLD and potential therapeutic strategies targeting FASN remain largely unknown.

Methods and Results

Through a systematic interactomics analysis of FASN‐complex proteins, we screened and identified sorting nexin 8 (SNX8) as a binding partner of FASN. SNX8 directly bound to FASN and promoted FASN ubiquitination and subsequent proteasomal degradation. We further demonstrated that SNX8 mediated FASN protein degradation by recruiting the E3 ligase tripartite motif containing 28 (TRIM28) and enhancing the TRIM28–FASN interaction. Notably, Snx8 interference in hepatocytes significantly deteriorated lipid accumulation in vitro, whereas SNX8 overexpression markedly blocked hepatocyte lipid deposition. Furthermore, the aggravating effect of Snx8 deletion on NAFLD was validated in vivo as hepatic steatosis and lipogenic pathways in the liver were significantly exacerbated in Snx8‐knockout mice compared to wild‐type controls. Consistently, hepatocyte‐specific overexpression of Snx8 in vivo markedly suppressed high‐fat, high‐cholesterol diet (HFHC)–induced hepatic steatosis. Notably, the protective effect of SNX8 against NAFLD was largely dependent on FASN suppression.

Conclusions

These data indicate that SNX8 is a key suppressor of NAFLD that promotes FASN proteasomal degradation. Targeting the SNX8–FASN axis is a promising strategy for NAFLD prevention and treatment.
Clinical value of INSL3 in the diagnosis and development of diabetic nephropathy
Authors: Zhu Jing , Zheng Xiang
Published: July 2021

Background

Insulin‐like factor 3 (INSL3) was stated to be an essential regulator in many diseases. This present study aimed to explore the underlying mechanisms of INSL3 in diabetic nephropathy (DN).

Methods

The serum samples were obtained from 121 DN patients, 67 T2DM patients, and 44 healthy controls. Twenty SD rats were used to establish the DN model in vivo. Quantitative PCR (qPCR) and Western blot were completed to analyze the INSL3 expression in cells, serum samples, and kidney of the rats. The structure of kidney was analyzed by HE staining. The diagnostic values of INSL3 in DN were determined by receiver operating characteristic (ROC) assay. Then, Spearman's correlation analysis was executed to verify the association between INSL3 and glomerular filtration rate (eGFR). Finally, the proliferation and apoptosis status of transfected cells were analyzed by MTT, flow cytometry, and Hoechst33258 staining assay.

Results

We found that INSL3 expression was up‐regulated in DN patients and SV40‐MES‐13 cells. Furthermore, the correlation analysis elucidated that INSL3 expression was negatively correlated with DN diagnosis golden criterion eGFR. INSL3 knockdown promoted the proliferation rate and inhibited the apoptosis rate of SV40‐MES‐13 cells after high‐glucose treatment. Finally, the INSL3 expression and fast blood glucose were up‐regulated in DN rats.

Conclusions

Collectively, this study demonstrated the clinical significance of INSL3 in diagnosing and developing DN.
Consumers Object to Algorithms Making Morally Relevant Tradeoffs Because of Algorithms’ Consequentialist Decision Strategies
Authors: Dietvorst Berkeley J. , Bartels Daniel M.
Published: July 2021

Why do consumers embrace some algorithms and find others objectionable? The moral relevance of the domain in which an algorithm operates plays a role. The authors find that consumers believe that algorithms are more likely to use maximization (i.e., attempting to maximize some measured outcome) as a decision‐making strategy than human decision makers (Study 1). Consumers find this consequentialist decision strategy to be objectionable in morally relevant tradeoffs and disapprove of algorithms making morally relevant tradeoffs as a result (Studies 2, 3a, & 3b). Consumers also object to human employees making morally relevant tradeoffs when they are trained to make decisions by maximizing outcomes, consistent with the notion that their objections to algorithmic decision makers stem from concerns about maximization (Study 4). The results provide insight into why consumers object to some consumer relevant algorithms while adopting others.
Physiologic and molecular characterization of a novel murine model of metastatic head and neck cancer cachexia
Authors: Olson Brennan , Norgard Mason A. , Levasseur Peter R. , Zhu Xinxia , Marks Daniel L.
Published: July 2021

Background

Cancer cachexia is a metabolic disorder characterized by the progressive loss of fat and lean mass that results in significant wasting, ultimately leading to reduced quality of life and increased mortality. Effective therapies for cachexia are lacking, potentially owing to the mismatch in clinically relevant models of cachexia. Specifically, cachexia observed in a clinical setting is commonly associated with advanced or late‐stage cancers that are metastatic, yet pre‐clinical metastatic models of cachexia are limited. Furthermore, the prevalence of cachexia in head and neck cancer patients is high, yet few pre‐clinical models of head and neck cancer cachexia exist. In addition to these shortcomings, cachexia is also heterogeneous among any given cancer, whereas patients with similar disease burden may experience significantly different degrees of cachexia symptoms. In order to address these issues, we characterize a metastatic model of human papilloma virus (HPV) positive head and neck squamous cell carcinoma that recapitulates the cardinal clinical and molecular features of cancer cachexia.

Methods

Male and female C57BL/6 mice were implanted subcutaneously with oropharyngeal squamous cell carcinoma cells stably transformed with HPV16 E6 and E7 together with hRas and luciferase (mEERL) that metastasizes to the lungs (MLM). We then robustly characterize the physiologic, behavioural, and molecular signatures during tumour development in two MLM subclones.

Results

Mice injected with MLM tumour cells rapidly developed primary tumours and eventual metastatic lesions to the lungs. MLM3, but not MLM5, engrafted mice progressively lost fat and lean mass during tumour development despite the absence of anorexia (P < 0.05). Behaviourally, MLM3‐implanted mice displayed decreased locomotor behaviours and impaired nest building (P < 0.05). Muscle catabolism programmes associated with cachexia, including E3 ubiquitin ligase and autophagy up‐regulation, along with progressive adipose wasting and accompanying browning gene signatures, were observed. Tumour progression also corresponded with hypothalamic and peripheral organ inflammation, as well as an elevation in neutrophil‐to‐lymphocyte ratio (P < 0.05). Finally, we characterize the fat and lean mass sparing effects of voluntary wheel running on MLM3 cachexia (P < 0.05).

Conclusions

This syngeneic MLM3 allograft model of metastatic cancer cachexia is reliable, consistent, and readily recapitulates key clinical and molecular features and heterogeneity of cancer cachexia. Because few metastatic models of cachexia exist—even though cachexia often accompanies metastatic progression—we believe this model more accurately captures cancer cachexia observed in a clinical setting and thus is well suited for future mechanistic studies and pre‐clinical therapy development for this crippling metabolic disorder.
Novel neural network optimization approach for modeling scattering and noise parameters of microwave transistor
Authors: Şenel Bilge , Şenel Fatih Ahmet
Published: July 2021

This study performed modeling of the scattering (S) and noise (N) parameters of the ATF53189 using the General Regression Neural Network (GRNN) and Multi Layer Perceptron Neural Network (MLPNN) methods based on Artificial Neural Network (ANN). For modeling the linear behavior of the transistor, the optimum design parameters of the GRNN and the MLPNN methods were determined using four different optimization algorithms. These are whale optimization algorithm (WOA), artificial bee colony (ABC), particle swarm optimization (PSO) and ant lion optimizer (ALO) algorithms. With the help of these algorithms, the sigma parameter of the GRNN and the number of hidden layers, numbers of neurons in the hidden layers and the activation functions of the hidden layers of the MLPNN were optimized. This way, the best models required for prediction of theSandNparameters of the ATF53189 were obtained. Different models that provided each of the angles and magnitudes of theS11,S21,S12,S22parameters and theFmin, Γmin, Γoptmagnitude, Γoptangle andRnnoise parameters as the output were created. The experimental results showed that the GRNN method should be used in linear behavior modeling ofSparameters of the ATF53189 and the MLPNN method should be used in linear behavior modeling ofNparameters of the ATF53189. It is understood that the best algorithm for optimizing the design parameters of the GRNN and the MLPNN methods is the PSO. As a result, the modeling of theSandNparameters of the ATF53189 transistor was successfully carried out with the methods used in this study.
Optimization of a Fabric Softener Formulation with an Electrochemical Sensor and Streaming Potential Measurements
Authors: Aničić Maja , Budetić Mateja , Dekanić Tihana , Grgić Katia , Pušić Tanja , Samardžić Mirela
Published: July 2021

An electrochemical, cationic, surfactant‐selective sensor based on multiwalled carbon nanotubes (MWCNT) functionalized with a sulfate group and the cetylpyridinium ion (MWCNT–OSO3−CP+) as a sensing material was used for optimization of the formulation of a fabric softener. Potentiometric titrations were performed and response measurements were obtained using four cationic surfactants (CS) of technical grade and four CS of analytical grade. The slope closest to Nernstian was obtained for di‐(tallow carboxyethyl) hydroxyethyl methylammonium methosulfate (MAS) (59.5 ± 1.1 mV/decade of activity in water and 57.5 ± 1.3 mV/decade of activity in CaCl2). When using CS as analytes in potentiometric titrations, the best accuracy (99.8%) was obtained when using MAS; therefore, it was chosen as the CS for the fabric softener formulation. Due to the better properties of fabric softeners with silicone in their formulations, four silicones at several concentration levels were used as potential additives. Based on the stability and viscosity of the system, the diquaternary polydimethylsiloxane (DPS) (w = 0.19%) was chosen for the fabric softener formulation. The pH did not significantly influence the potential when in the range of 3–8 or the recovery of potentiometric titrations when in the range of 3–7. The application profile of the CS was assessed through streaming potential measurements of reference fabrics in an electrokinetic analyzer. The obtained electrokinetic parameters indicated on lag in adsorption of model fabric softener (MFS) based on MAS (w = 9%), with the addition of silicone DPS (MFS 3), on cotton and polyester fabrics, but advantage in stability when compared with other MFS investigated.
Effect of Pore Size of Honeycomb‐Patterned Polymer Film on Spontaneous Formation of 2D Micronetworks by Coculture of Human Umbilical Vein Endothelial Cells and Mesenchymal Stem Cells
Authors: Oku Keisuke , Ohno Kyohei , Miyamoto Daisuke , Ito Koju , Yabu Hiroshi , Nakazawa Kohji
Published: July 2021

The geometrical control of micronetwork structures (NSs) formed by endothelial cells is an important topic in tissue engineering, cell‐based assays, and fundamental biological studies. In this study, NSs are formed using human umbilical vein endothelial cells (HUVECs) by the coculture of HUVECs and human mesenchymal stem cells (MSCs) confined in a honeycomb‐patterned poly‐l‐lactic acid film (honeycomb film (HCF)), which is a novel cell culture scaffold. The HCF is produced using the breath figure method, which uses condensed water droplets as pore templates. The confinement of the HUVECs and MSCs in the HCF along with the application of centrifugal force results in NS formation when the pore size is more than 20 m. Furthermore, NS development is geometrically restricted by the hexagonally packed and connected pores in the horizontal direction of the HCF. Network density is also controlled by changing the seeding density of the HUVECs and MSCs. The threshold pore size indicates that NSs can be formed spontaneously by using an HCF with a perfectly uniform porous structure. This result provides an important design guideline for the structure of porous cell culture scaffolds by applying a blood vessel model in vitro.
Local temperature forecasts based on statistical post‐processing of numerical weather prediction data
Authors: Alerskans Emy , Kaas Eigil
Published: July 2021

Six adaptive, short‐term post‐processing methods for correcting systematic errors in numerical weather prediction (NWP) forecasts of near‐surface air temperatures using local meteorological observations are assessed and compared. The methods tested are based on the simple moving average and the more advanced Kalman filter. Forecasts from the rather coarse‐resolution global NWP model Global Forecast System (GFS) and the regional high‐resolution NWP model HARMONIE are post‐processed, and the results are evaluated for 100 private weather stations in Denmark. The performance of the post‐processing methods differs depending on the NWP model. Overall, the combined moving average and a so‐called lead time Kalman filter performs the best. The moving average was shown to be superior to a diurnal bias correction Kalman filter at removing the longer‐term systematic errors for HARMONIE forecast data and comparable for GFS forecast data. Subsequent application of the lead time Kalman filter corrects for the short‐term errors using the real‐time forecast error. The post‐processing method is adaptive and there is no need for a long record of observations or a historical archive of forecasts.
Noninvasive assessment of myocardial energy metabolism and dynamics using in vivo deuterium MRS imaging
Authors: Wang Tao , Zhu Xiao‐Hong , Li Huan , Zhang Yi , Zhu Wei , Wiesner Hannes M. , Chen Wei
Published: July 2021

Purpose

The assessment of cellular energy metabolism is crucial for understanding myocardial physiopathology. Here, we conducted a pilot study to develop an alternative imaging approach for the assessment of myocardial energy metabolism.

Methods

We developed a deuterium MRSI method to noninvasively monitor the accumulation of deuterated downstream metabolites and deuterated water in rat hearts infused with deuterated glucose or acetate substrate on a 16.4 Tesla animal scanner.

Results

We found that the deuterated water accumulation rate and isotopic turnover rate of deuterated glutamate/glutamine via the tricarboxylic acid cycle and exchange in rat hearts were much higher when infused with acetate compared to that with glucose, demonstrating the myocardium substrate preference for acetate over glucose.

Conclusion

We demonstrated the feasibility of deuterium MRSI for noninvasive imaging and assessment of myocardial energy metabolism in vivo. Although the strong signal and large dynamics of myocardial deuterated water may provide a sensitive imaging biomarker, quantifying the metabolic rates still poses a challenge due to the confounding effects of blood recirculation, perfusion, and multiple deuterated water production pathways. In contrast, the deuterated glutamate/glutamine signal and change should directly reflect the metabolic activity of the myocardial tricarboxylic acid cycle, which can be used to study the metabolic shift in substance preference between acetate and glucose in the diseased state. Deuterium MRSI is noninvasive and robust and may have the potential to assess myocardial energy metabolism in human patients.
Adiposity and muscle mass phenotyping is not superior to BMI in detecting cardiometabolic risk in a cross‐sectional study
Authors: Kakinami Lisa , Danieles Prince Kevin , Ajibade Kehinde , Santosa Sylvia , Murphy Jessica
Published: July 2021

Objective

Classifying adiposity based on dual‐energy x‐ray absorptiometry (DXA) muscle and fat mass phenotypes has been proposed. Whether these phenotypes are more accurate in predicting cardiometabolic risk than BMI weight status is unknown.

Methods

Data were from the National Health and Nutrition Examination Survey (NHANES; 1999‐2006 cycles, n = 5,475). Weight status was defined by BMI. Phenotypes of adiposity and muscle were based on high (≥50th percentile) and low (<50th percentile) permutations of sex‐ and age‐specific fat and muscle mass population curves. The area under the curves of receiver operating characteristic curves (ROC‐AUCs), which predicted the presence of abnormal lipids, glucose, and blood pressure, were compared. All analyses were stratified by sex and incorporated the complex survey design and weighting of NHANES.

Results

The ROC‐AUCs from weight status models used to correctly identify cardiometabolic risk ranged from 0.57 to 0.68, indicating generally weak predictive power. However, the ROC‐AUCs from DXA phenotypes were lower (ranging from 0.53‐0.68), indicating weaker predictive power than weight status, and were statistically inferior for nearly all of the comparisons.

Conclusions

Despite DXA’s high cost and detailed output regarding body composition, its phenotype classification was inferior to weight status in predicting cardiometabolic risk. Further studies investigating the utility of the phenotypes are needed.
Differential expression of genes associated with non‐target site resistance in Poa annua with target site resistance to acetolactate synthase inhibitors
Authors: Laforest Martin , Soufiane Brahim , Patterson Eric L , Vargas José J , Boggess Sarah L , Houston Logan C , Trigiano Robert N , Brosnan James T
Published: July 2021

BACKGROUND

Poa annua is a pervasive grassy, self‐pollinating, weed that has evolved resistance to 10 different herbicide modes‐of‐action, third most of all weed species. We investigated constitutive overexpression of genes associated with non‐target site resistance (NTSR) in POAAN‐R3 and the response of those genes when treated with trifloxysulfuron despite the biotype having a known target site mutation in acetolactate synthase (ALS).

RESULTS

Despite having an ALS target site mutation, POAAN‐R3 still had a transcriptomic response to herbicide application that differed from a susceptible biotype. We observed differential expression of genes associated with transmembrane transport and oxidation–reduction activities, with differences being most pronounced prior to herbicide treatment.

CONCLUSIONS

In the P. annua biotype we studied with confirmed target site resistance to ALS inhibitors, we also observed constitutive expression of genes regulating transmembrane transport, as well as differential expression of genes associated with oxidative stress after treatment with trifloxysulfuron. This accumulation of mechanisms, in addition to the manifestation of target site resistance, could potentially increase the chance of survival when plants are challenged by different modes of action.
Field‐evolved resistance to 11 insecticides and the mechanisms involved in Helicoverpa armigera (Lepidoptera: Noctuidae)
Authors: Wang Qinqin , Rui Changhui , Wang Li , Nahiyoon Shahzad Ali , Huang Weiling , Zhu Junshu , Ji Xuejiao , Yang Qingjie , Yuan Huizhu , Cui Li
Published: July 2021

BACKGROUND

To understand the ongoing resistance of cotton bollworm, Helicoverpa armigera, the sensitivity of five field populations to commonly used insecticides, indoxacarb, abamectin, methoxyfenozide, chlorfenapyr, chlorantraniliprole, spinetoram, lambda‐cyhalothrin, carbosulfan, metaflumizone, chlorpyrifos, and flufenoxuron, were evaluated. Furthermore, the biochemical and molecular mechanisms of field‐evolved resistance in H. armigera were also investigated.

RESULTS

Five field populations of H. armigera showed moderate resistance to indoxacarb, chlorantraniliprole, metaflumizone, methoxyfenozide, carbosulfan and lambda‐cyhalothrin. The resistance ratio (RR) of indoxacarb was significantly correlated with glutathione‐S‐transferases (GSTs) activity (r = 0.913, P = 0.011). Methoxyfenozide RR was largely correlated with cytochrome P450s activity (r = 0.860, P = 0.028). Besides, six cytochrome P450s genes of CYP4L5 in AQP, CYP6B7 and CYP9A14 in HDP and BDP, CYP9A17V2 in HDP and YSP, CYP332A1 in HDP, LFP, AQP and YSP, CYP337B1 in YSP, and two GSTs genes of GSTd1 and GSTs1 in HDP were overexpressed (>5‐fold). Moreover, indoxacarb RR was positively correlated with the overexpression of GSTs1, GSTd1 and CYP9A14 genes (r = 0.880, 0.98 and 0.86, P = 0.021, 0.001 and 0.028, respectively). The transcript of CYP9A17V2 and CYP337B1 were found to be correlated with metaflumizone RR (r = 0.950, P = 0.004) and carbosulfan RR (r = 0.850, P = 0.033), respectively.

CONCLUSION

H. armigera can be effectively controlled using abamectin, chlorfenapyr, chlorpyrifos and spinetoram in Hebei and Shandong provinces. The present study demonstrated that the relative expression level of GSTs1, GSTd1, CYP9A14, CYP9A17V2 and CYP337B1 genes were significantly correlated with the resistance ratio to indoxacarb, metaflumizone and carbosulfan in field H. armigera.
Forecast verification: Relating deterministic and probabilistic metrics
Authors: Leung Tsz Yan , Leutbecher Martin , Reich Sebastian , Shepherd Theodore G.
Published: July 2021

The philosophy of forecast verification is rather different between deterministic and probabilistic verification metrics: generally speaking, deterministic metrics measure differences, whereas probabilistic metrics assess reliability and sharpness of predictive distributions. This article considers the root‐mean‐square error (RMSE), which can be seen as a deterministic metric, and the probabilistic metric Continuous Ranked Probability Score (CRPS), and demonstrates that under certain conditions, the CRPS can be mathematically expressed in terms of the RMSE when these metrics are aggregated. One of the required conditions is the normality of distributions. The other condition is that, while the forecast ensemble need not be calibrated, any bias or over/underdispersion cannot depend on the forecast distribution itself. Under these conditions, the CRPS is a fraction of the RMSE, and this fraction depends only on the heteroscedasticity of the ensemble spread and the measures of calibration. The derived CRPS–RMSE relationship for the case of perfect ensemble reliability is tested on simulations of idealised two‐dimensional barotropic turbulence. Results suggest that the relationship holds approximately despite the normality condition not being met.
Response to comment
Authors: Okun Pavel , Burke Kieron
Published: July 2021

See related comment article by Turbiner et al.
Founder team prior work experience: An asset or a liability for startup growth?
Authors: Hashai Niron , Zahra Shaker
Published: July 2021

Research Summary

We examine the effects of founder teams' firm‐ and industry prior work experience on startup growth in the context of high technology industries. We study these effects both on the early growth of startups and on their growth, after accumulating experiential knowledge. Integrating the literatures on human capital, imprinting and competency traps, we develop a typology of four combinations of founder prior experience: founder same firm and same industry experience, founder same industry but other firm experience, founder same firm but other‐industry experience, and founder other‐industry and other firm experience. Using data from 153 Israeli high technology startups, we find significant variations in the effects of these combinations on startup growth, which also vary between the early and later years of these startups.

Managerial Summary

Founders play a key role in the lives of their startups, applying their resources, knowledge and experience. Therefore, we ask: how does founder experience influence high technology startups' growth? To answer this question, we examine four combinations of founder prior experience: founder same firm and same industry experience, founder same industry but not same firm experience, founder same firm but other‐industry experience, and founder other‐industry and not same firm experience. Our analyses show significant differences in startup growth based on these combinations of founder prior experience and, importantly, the effect of these four combinations on startups' growth in their early years of existence differs significantly from later years, when these firms can increasingly draw on their own experiential learning.
Effect of SiO2 and TiO2 on the Crystal Morphology of CaF2Al2O3CaO‐Based Electroslag Remelting Slag
Authors: Xu Rong-huan , Guo Jing , Zhang Man-cang , Guo Han-jie
Published: July 2021

The eﬀect of SiO2 and TiO2 on the crystal morphology of 60%CaF220%Al2O320%CaO‐type electroslag remelting (ESR) slags are investigated by thermodynamic simulations, differential scanning calorimetry, X‐ray diffraction, scanning electron microscope, and energy dispersive X‐ray spectroscopy. The results suggest that the addition of TiO2 and SiO2 changes the type, amount, and sequence of crystal precipitation. CaF2 is confirmed to be the main crystalline phase in the slag, the morphology of which depends on the slag composition and cooling rate: As SiO2 content increases, the crystal morphology of CaF2 in the slag changes from dendrites with smooth surface and relatively large secondary dendrite arm spacing to dendrites with sharp tips and relatively small secondary and tertiary dendritic arm spacings. A classical crystallographic model, Jackson α factor, is proved to correctly predict the crystal morphology as observed in the experiments. It is inferred that the addition of 5 wt% TiO2 and 4 wt% SiO2 and a proper cooling rate are favorable to improve the lubrication property of 60%CaF220%Al2O320%CaO‐type ESR slags.
A new wake‐merging method for wind‐farm power prediction in the presence of heterogeneous background velocity fields
Authors: Lanzilao Luca , Meyers Johan
Published: July 2021

The difference in surface roughness between land and sea, and the terrain complexities, lead to spatially heterogeneous atmospheric conditions, and therefore affect the propagation and dynamics of wind‐turbine and wind‐farm wakes. Currently, these flow heterogeneities and their effects on plant aerodynamics are not modeled in the majority of engineering wake models. In this study, we address this issue by developing a new wake‐merging method capable of superimposing the waked flow on a heterogeneous background velocity field. We couple the proposed wake‐merging method with four different wake models, i.e. the Gaussian, super‐Gaussian, double‐Gaussian and Ishihara model, and we test its performance against LES results, dual‐Doppler radar measurements and SCADA data from the Horns Rev, London Array, and Westermost Rough farms. The standard Jensen model with quadratic superposition is also included. In homogeneous conditions, the new method predicts slightly higher velocity deficits than the linear superposition method. Overall, the distributions of the difference in power ratio between the two wake‐merging methods predictions and observations show a similar mean absolute error (MAE) and interquartile range (IQR) in such conditions. On the other hand, the new wake‐merging method predictions display a lower MAE with a similar IQR in case of a spatially varying background velocity, being overall more accurate than the ones obtained with linear superposition. The most accurate estimates are obtained when the wake‐merging methods are coupled with the double‐Gaussian and Gaussian single‐wake models. In contrast, the Jensen and super‐Gaussian wake models overestimate the velocity deficits for the majority of cases analyzed.
Naturally light Dirac neutrinos from SU(6)
Authors: Ma Ernest
Published: July 2021

Abstract

A known mechanism for obtaining naturally light Dirac neutrinos is implemented in the context of SU(6) → SU(5) × U(1)N.
Die Corona-Pandemie und Multiple Sklerose: Impfungen und deren Implikationen für Patienten – Teil 2: Impfstofftechnologien
Authors: Monschein Tobias , Zrzavy Tobias , Löbermann Micha , Winkelmann Alexander , Berger Thomas , Rommer Paulus , Hartung Hans-Peter , Zettl Uwe K.
Published: July 2021

Im Zusammenhang mit den Herausforderungen durch die weltweit vorherrschende COVID-19-Pandemie kam es zu teils epochalen Fortschritten im Bereich der Impfstofftechnologien. Neben den bereits langjährig eingesetzten Tot‑, Lebend- und proteinbasierten Impfstoffen gewannen im Zuge dieser Gesundheitskrise vektor- und genbasierte Impfstoffe enorm an Bedeutung. Ziel dieser Arbeit ist es daher, einen Überblick über Multiple Sklerose und Impfen, rezente Fortschritte in der SARS-CoV-2-Impfstoff-Landschaft sowie eine detaillierte Auseinandersetzung mit den verschiedenen Impfstofftechnologien zu bieten. Abschließend sollen übersichtsmäßig klare Empfehlungen im Zusammenhang mit krankheitsmodifizierenden Therapien und Impfen bei Multiple Sklerose gegeben werden.
Zwei Fälle kardialer Sarkoidose als Ursache des plötzlichen Herztodes
Authors: Schwarz Clara-Sophie , Weis Cleo-Aron , Marx Alexander , Germerott Tanja , Walz Cleo
Published: July 2021

Eine der primären Aufgaben der Rechtsmedizin ist die Aufklärung unerwarteter Todesfälle. Speziell das Erkennen seltener Todesursachen setzt ein fundiertes Wissen um die typischen makromorphologischen Befunde sowie das Einleiten und die Interpretation entsprechend geeigneter Ergänzungsuntersuchungen, etwa histologischer Verfahren, voraus. Wichtige Differenzialdiagnosen müssen bekannt sein, damit die Todesursache mit vertretbarem diagnostischem Aufwand festgestellt werden kann.

In der vorliegenden Arbeit werden charakteristische makroskopische und mikroskopische Befunde der kardialen Sarkoidose (oder granulomatösen Myokarditis) und deren Abgrenzung zur Riesenzellmyokarditis anhand von 2 Fällen demonstriert. In beiden Fällen gab der plötzliche Tod einer erwachsenen Person mittleren Alters Anlass zu einer gerichtlichen Obduktion, die jeweils zur Diagnose einer kardialen Sarkoidose führte. Die unterschiedlichen Krankheitsverläufe und Befunde werden unter Berücksichtigung einschlägiger wissenschaftlicher Literatur diskutiert. Durch eine sorgfältige Erhebung der Vorgeschichte und der makromorphologischen Befunde kann die Verdachtsdiagnose einer kardialen Sarkoidose unmittelbar nach der Obduktion geäußert und durch histopathologische Untersuchungen bestätigt werden. Es wird deutlich, dass eine interdisziplinäre Fallarbeit bei seltenen Erkrankungen wie der kardialen Sarkoidose eine schnelle Diagnose ermöglicht.