bluuebunny/crossref_metadata_2025 huggingface dataset:
Sox9 and Rbpj differentially regulate endothelial to mesenchymal transition and wound scarring in murine endovascular progenitors
Authors: Zhao Jilai , Patel Jatin , Kaur Simranpreet , Sim Seen-Ling , Wong Ho Yi , Styke Cassandra , Hogan Isabella , Kahler Sam , Hamilton Hamish , Wadlow Racheal , Dight James , Hashemi Ghazaleh , Sormani Laura , Roy Edwige , Yoder Mervin C. , Francois Mathias , Khosrotehrani Kiarash
Published: May 2021

Endothelial to mesenchymal transition (EndMT) is a leading cause of fibrosis and disease, however its mechanism has yet to be elucidated. The endothelium possesses a profound regenerative capacity to adapt and reorganize that is attributed to a population of vessel-resident endovascular progenitors (EVP) governing an endothelial hierarchy. Here, using fate analysis, we show that two transcription factors SOX9 and RBPJ specifically affect the murine EVP numbers and regulate lineage specification. Conditional knock-out of Sox9 from the vasculature (Sox9fl/fl/Cdh5-CreERRosaYFP) depletes EVP while enhancing Rbpj expression and canonical Notch signalling. Additionally, skin wound analysis from Sox9 conditional knock-out mice demonstrates a significant reduction in pathological EndMT resulting in reduced scar area. The converse is observed with Rbpj conditionally knocked-out from the murine vasculature (Rbpjfl/fl/Cdh5-CreER RosaYFP) or inhibition of Notch signaling in human endothelial colony forming cells, resulting in enhanced Sox9 and EndMT related gene (Snail, Slug, Twist1, Twist2, TGF-β) expression. Similarly, increased endothelial hedgehog signaling (Ptch1fl/fl/Cdh5-CreER RosaYFP), that upregulates the expression of Sox9 in cells undergoing pathological EndMT, also results in excess fibrosis. Endothelial cells transitioning to a mesenchymal fate express increased Sox9, reduced Rbpj and enhanced EndMT. Importantly, using topical administration of siRNA against Sox9 on skin wounds can substantially reduce scar area by blocking pathological EndMT. Overall, here we report distinct fates of EVPs according to the relative expression of Rbpj or Notch signalling and Sox9, highlighting their potential plasticity and opening exciting avenues for more effective therapies in fibrotic diseases.
Co-evolution of tumor and immune cells during progression of multiple myeloma
Authors: Liu Ruiyang , Gao Qingsong , Foltz Steven M. , Fowles Jared S. , Yao Lijun , Wang Julia Tianjiao , Cao Song , Sun Hua , Wendl Michael C. , Sethuraman Sunantha , Weerasinghe Amila , Rettig Michael P. , Storrs Erik P. , Yoon Christopher J. , Wyczalkowski Matthew A. , McMichael Joshua F. , Kohnen Daniel R. , King Justin , Goldsmith Scott R. , O’Neal Julie , Fulton Robert S. , Fronick Catrina C. , Ley Timothy J. , Jayasinghe Reyka G. , Fiala Mark A. , Oh Stephen T. , DiPersio John F. , Vij Ravi , Ding Li
Published: May 2021

Multiple myeloma (MM) is characterized by the uncontrolled proliferation of plasma cells. Despite recent treatment advances, it is still incurable as disease progression is not fully understood. To investigate MM and its immune environment, we apply single cell RNA and linked-read whole genome sequencing to profile 29 longitudinal samples at different disease stages from 14 patients. Here, we collect 17,267 plasma cells and 57,719 immune cells, discovering patient-specific plasma cell profiles and immune cell expression changes. Patients with the same genetic alterations tend to have both plasma cells and immune cells clustered together. By integrating bulk genomics and single cell mapping, we track plasma cell subpopulations across disease stages and find three patterns: stability (from precancer to diagnosis), and gain or loss (from diagnosis to relapse). In multiple patients, we detect “B cell-featured” plasma cell subpopulations that cluster closely with B cells, implicating their cell of origin. We validate AP-1 complex differential expression (JUN and FOS) in plasma cell subpopulations using CyTOF-based protein assays, and integrated analysis of single-cell RNA and CyTOF data reveals AP-1 downstream targets (IL6 and IL1B) potentially leading to inflammation regulation. Our work represents a longitudinal investigation for tumor and microenvironment during MM progression and paves the way for expanding treatment options.
Balanced imitation sustains song culture in zebra finches
Authors: Tchernichovski Ofer , Eisenberg-Edidin Sophie , Jarvis Erich D.
Published: May 2021

Songbirds acquire songs by imitation, as humans do speech. Although imitation should drive convergence within a group and divergence through drift between groups, zebra finch songs sustain high diversity within a colony, but mild variation across colonies. We investigated this phenomenon by analyzing vocal learning statistics in 160 tutor-pupil pairs from a large breeding colony. Song imitation is persistently accurate in some families, but poor in others. This is not attributed to genetic differences, as fostered pupils copied their tutors’ songs as accurately or poorly as biological pupils. Rather, pupils of tutors with low song diversity make more improvisations compared to pupils of tutors with high song diversity. We suggest that a frequency dependent balanced imitation prevents extinction of rare song elements and overabundance of common ones, promoting repertoire diversity within groups, while constraining drift across groups, which together prevents the collapse of vocal culture into either complete uniformity or chaos.
Subtelomeric assembly of a multi-gene pathway for antimicrobial defense compounds in cereals
Authors: Li Yan , Leveau Aymeric , Zhao Qiang , Feng Qi , Lu Hengyun , Miao Jiashun , Xue Zheyong , Martin Azahara C. , Wegel Eva , Wang Jing , Orme Anastasia , Rey Maria-Dolores , Karafiátová Miroslava , Vrána Jan , Steuernagel Burkhard , Joynson Ryan , Owen Charlotte , Reed James , Louveau Thomas , Stephenson Michael J. , Zhang Lei , Huang Xuehui , Huang Tao , Fan Danling , Zhou Congcong , Tian Qilin , Li Wenjun , Lu Yiqi , Chen Jiaying , Zhao Yan , Lu Ying , Zhu Chuanrang , Liu Zhenhua , Polturak Guy , Casson Rebecca , Hill Lionel , Moore Graham , Melton Rachel , Hall Neil , Wulff Brande B. H. , Doležel Jaroslav , Langdon Tim , Han Bin , Osbourn Anne
Published: May 2021

Non-random gene organization in eukaryotes plays a significant role in genome evolution. Here, we investigate the origin of a biosynthetic gene cluster for production of defence compounds in oat—the avenacin cluster. We elucidate the structure and organisation of this 12-gene cluster, characterise the last two missing pathway steps, and reconstitute the entire pathway in tobacco by transient expression. We show that the cluster has formed de novo since the divergence of oats in a subtelomeric region of the genome that lacks homology with other grasses, and that gene order is approximately colinear with the biosynthetic pathway. We speculate that the positioning of the late pathway genes furthest away from the telomere may mitigate against a ‘self-poisoning’ scenario in which toxic intermediates accumulate as a result of telomeric gene deletions. Our investigations reveal a striking example of adaptive evolution underpinned by remarkable genome plasticity.
Development of a valid Chinese version of the Cumberland Ankle Instability Tool in Chinese-speaking patients with chronic ankle instability disorders
Authors: Wang Wei , Liao Dongfa , Kang Xia , Zheng Wei , Xu Wei , Chen Song , Xie Qingyun
Published: May 2021

As an effective scale for the condition assessment of patients with chronic ankle instability (CAI), the Cumberland Ankle Instability Tool (CAIT) is the most widely used scale, and its original version is written in English. Therefore, the purpose of our study is to apply the CAIT to Chinese patients and evaluate its responsiveness, reliability, and validity in terms of Chinese patients with CAI. First, we adapted the CAIT into the Chinese edition (CAIT-C), through which cross-cultural adaptation and translation can be carried out in a five-step procedure. Next, recruited patients completed the three periods of the Foot and Ankle Ability Measure (FAAM), CAIT-C, and the Medical Outcomes Study Short-Form 36 (SF-36) scales. Afterward, to assess the responsiveness, reliability, and validity, we calculated the standardized response mean (SRM), effect size (ES), Spearman's correlation coefficient (rs), minimal detectable change (MDC), standard error of measurement (SEM), intraclass correlation coefficient (ICC), and Cronbach’s alpha. Generally, in the use of CAI, 131, 119, and 86 patients favorably completed the three periods of the scales. The CAIT-C was proven to have good test–retest reliability (ICC = 0.930) and fine internal consistency (Cronbach’s alpha = 0.845–0.878). The low-value of MDC (0.04–2.28) and SEM (1.73) show it is possible to detect clinical changes when we take advantage of CAIT-C. Good or moderate correlations (rs = 0.422–0.738) were gained from the physical subscales of the SF-36 and the subscales of the FAAM and the CAIT-C. Fair or poor correlations (rs = 0.003–0.360) were gained between the mental subscales of the SF-36 and the CAIT-C, which sufficiently indicated that the CAIT-C had good validity. Moreover, good responsiveness was observed in the CAIT-C (ES = 1.316, SRM = 1.418). The CAIT-C scale is an effective, valid, and reliable tool to evaluate Chinese CAI patients.
Inter-laboratory comparison of gene expression biodosimetry for protracted radiation exposures as part of the RENEB and EURADOS WG10 2019 exercise
Authors: Abend M. , Amundson S. A. , Badie C. , Brzoska K. , Hargitai R. , Kriehuber R. , Schüle S. , Kis E. , Ghandhi S. A. , Lumniczky K. , Morton S. R. , O’Brien G. , Oskamp D. , Ostheim P. , Siebenwirth C. , Shuryak I. , Szatmári T. , Unverricht-Yeboah M. , Ainsbury E. , Bassinet C. , Kulka U. , Oestreicher U. , Ristic Y. , Trompier F. , Wojcik A. , Waldner L. , Port M.
Published: May 2021

Large-scale radiation emergency scenarios involving protracted low dose rate radiation exposure (e.g. a hidden radioactive source in a train) necessitate the development of high throughput methods for providing rapid individual dose estimates. During the RENEB (Running the European Network of Biodosimetry) 2019 exercise, four EDTA-blood samples were exposed to an Iridium-192 source (1.36 TBq, Tech-Ops 880 Sentinal) at varying distances and geometries. This resulted in protracted doses ranging between 0.2 and 2.4 Gy using dose rates of 1.5–40 mGy/min and exposure times of 1 or 2.5 h. Blood samples were exposed in thermo bottles that maintained temperatures between 39 and 27.7 °C. After exposure, EDTA-blood samples were transferred into PAXGene tubes to preserve RNA. RNA was isolated in one laboratory and aliquots of four blinded RNA were sent to another five teams for dose estimation based on gene expression changes. Using an X-ray machine, samples for two calibration curves (first: constant dose rate of 8.3 mGy/min and 0.5–8 h varying exposure times; second: varying dose rates of 0.5–8.3 mGy/min and 4 h exposure time) were generated for distribution. Assays were run in each laboratory according to locally established protocols using either a microarray platform (one team) or quantitative real-time PCR (qRT-PCR, five teams). The qRT-PCR measurements were highly reproducible with coefficient of variation below 15% in ≥ 75% of measurements resulting in reported dose estimates ranging between 0 and 0.5 Gy in all samples and in all laboratories. Up to twofold reductions in RNA copy numbers per degree Celsius relative to 37 °C were observed. However, when irradiating independent samples equivalent to the blinded samples but increasing the combined exposure and incubation time to 4 h at 37 °C, expected gene expression changes corresponding to the absorbed doses were observed. Clearly, time and an optimal temperature of 37 °C must be allowed for the biological response to manifest as gene expression changes prior to running the gene expression assay. In conclusion, dose reconstructions based on gene expression measurements are highly reproducible across different techniques, protocols and laboratories. Even a radiation dose of 0.25 Gy protracted over 4 h (1 mGy/min) can be identified. These results demonstrate the importance of the incubation conditions and time span between radiation exposure and measurements of gene expression changes when using this method in a field exercise or real emergency situation.
Tracking the time course of reproduction number and lockdown’s effect on human behaviour during SARS-CoV-2 epidemic: nonparametric estimation
Authors: Pillonetto G. , Bisiacco M. , Palù G. , Cobelli C.
Published: May 2021

Understanding the SARS-CoV-2 dynamics has been subject of intense research in the last months. In particular, accurate modeling of lockdown effects on human behaviour and epidemic evolution is a key issue in order e.g. to inform health-care decisions on emergency management. In this regard, the compartmental and spatial models so far proposed use parametric descriptions of the contact rate, often assuming a time-invariant effect of the lockdown. In this paper we show that these assumptions may lead to erroneous evaluations on the ongoing pandemic. Thus, we develop a new class of nonparametric compartmental models able to describe how the impact of the lockdown varies in time. Our estimation strategy does not require significant Bayes prior information and exploits regularization theory. Hospitalized data are mapped into an infinite-dimensional space, hence obtaining a function which takes into account also how social distancing measures and people’s growing awareness of infection’s risk evolves as time progresses. This also permits to reconstruct a continuous-time profile of SARS-CoV-2 reproduction number with a resolution never reached before in the literature. When applied to data collected in Lombardy, the most affected Italian region, our model illustrates how people behaviour changed during the restrictions and its importance to contain the epidemic. Results also indicate that, at the end of the lockdown, around$$12\%$$12%of people in Lombardy and$$5\%$$5%in Italy was affected by SARS-CoV-2, with the fatality rate being 1.14%. Then, we discuss how the situation evolved after the end of the lockdown showing that the reproduction number dangerously increased in the summer, due to holiday relax, reaching values larger than one on August 1, 2020. Finally, we also document how Italy faced the second wave of infection in the last part of 2020. Since several countries still observe a growing epidemic and others could be subject to other waves, the proposed reproduction number tracking methodology can be of great help to health care authorities to prevent SARS-CoV-2 diffusion or to assess the impact of lockdown restrictions on human behaviour to contain the spread.
Intestinal mucosa-derived DNA methylation signatures in the penetrating intestinal mucosal lesions of Crohn’s disease
Authors: Li Yuan , Wang Zhiming , Wu Xiuwen , Wang Gefei , Gu Guosheng , Ren Huajian , Hong Zhiwu , Ren Jianan
Published: May 2021

The purpose of this study was to evaluate genome-wide DNA methylation changes in intestinal mucosa tissue of adult patients with Crohn's disease comprehensively. DNA methylation chip was used to analyze abnormal methylation sites among penetrating and non-penetrating intestinal mucosa tissue of Crohn's disease and normal intestinal mucosa tissue of healthy controls. Methylation abnormalities of different locus were verified by pyrosequencing and quantitative polymerase chain reaction. Differential DNA methylation sites were participated in the positive regulation of apoptosis and the positive regulation of IL-8 production and were enriched in signaling pathways related to inflammatory bowel disease and extracellular matrix receptor interaction signaling pathways. Correlation analysis showed that the methylation abnormalities of HLA-DRB1 (r = − 0.62, P < 0.001), MUC1 (r = − 0.45, P = 0.01), YPEL5 (r = − 0.55, P = 0.001) and CBLB (r = − 0.62, P < 0.001) were significantly negatively correlated with their relative expression levels. The degree of methylation abnormality of MUC1 was negatively correlated with the disease activity score of Crohn's disease (r = − 0.50, P = 0.01). Apoptosis, interleukin-8 production and abnormal extracellular matrix might be involved in the mechanism of penetrating intestinal mucosal lesions in Crohn's disease. The degree of abnormal methylation of MUC1 was negatively correlated with the disease activity of Crohn's disease.
Immunocompatibility of a new dual modality contrast agent based on radiolabeled iron-oxide nanoparticles
Authors: Karageorgou Maria-Argyro , Stamopoulos Dimosthenis
Published: May 2021

Radiolabeled magnetic nanoparticles are promising candidates as dual-modality-contrast-agents (DMCA) for diagnostic applications. The immunocompatibility of a new DMCA is a prerequisite for subsequent in vivo applications. Here, a new DMCA, namely Fe3O4 nanoparticles radiolabeled with 68Ga, is subjected to immunocompatibility tests both in vitro and in vivo. The in vitro immunocompatibility of the DMCA relied on incubation with donated human WBCs and PLTs (five healthy individuals). Optical microscopy (OM) and atomic force microscopy (AFM) were employed for the investigation of the morphological characteristics of WBCs and PLTs. A standard hematology analyzer (HA) provided information on complete blood count. The in vivo immunocompatibility of the DMCA was assessed through its biodistribution among the basic organs of the mononuclear phagocyte system in normal and immunodeficient mice (nine in each group). In addition, Magnetic Resonance Imaging (MRI) data were acquired in normal mice (three). The combined OM, AFM and HA in vitro data showed that although the DMCA promoted noticeable activation of WBCs and PLTs, neither degradation nor clustering were observed. The in vivo data showed no difference of the DMCA biodistribution between the normal and immunodeficient mice, while the MRI data prove the efficacy of the particular DMCA when compared to the non-radiolabeled, parent CA. The combined in vitro and in vivo data prove that the particular DMCA is a promising candidate for future in vivo applications.
Understanding the structural, optical, and dielectric characteristics of SrLaLiTe1−xMnxO6 perovskites
Authors: Halizan M. Z. M. , Mohamed Z. , Yahya A. K.
Published: May 2021

In electronic applications, good dielectric permittivity material has huge potential in the capacitive energy storage devices. Herein, in the present work the dielectric study of SrLaLiTe1−xMnxO6(x = 0.02, 0.04, 0.06, 0.08, and 0.10) double perovskites has been studied and discussed. These compounds were prepared through solid-state reaction method. All of the prepared compounds were confirmed to crystallized in monoclinic structure ofP21/nspace symmetry with better crystallization when dopant concentrations increased untilx = 0.08. The formation of Li–O–Te/Mn bonds in octahedral structures in all compounds were confirmed in this study. The existence of peaks at specific wavenumbers indicated vibrations of B–site cations’ bonds. When dopant amounts were increased fromx = 0.02 tox = 0.08, there was an increasing trend of grains sizes formation in the compounds. The discussions on effects of grain sizes towards dielectric properties were included in this paper. Other important results and discussions comprised of the significant effects of dopant on the optical band gap (Eopt) and absorption frequencies of the compounds. The decreasing trend ofEopttowards semiconductor range indicated the compounds’ promising potentials for optoelectronic device application.
High loading of trimethylglycine promotes aqueous solubility of poorly water-soluble cisplatin
Authors: Kadokawa Riki , Fujie Tetsuo , Sharma Gyanendra , Ishibashi Kojiro , Ninomiya Kazuaki , Takahashi Kenji , Hirata Eishu , Kuroda Kosuke
Published: May 2021

Trimethylglycine (TMG) is a cheap, natural, and highly biocompatible compound. Therefore, it has been used in the fields of food and life sciences, but the application of solid TMG is limited to utilisation as an “additive”. In the present study, we focussed on the high solubility of TMG in water, derived from the aprotic zwitterionic structure, and proposed TMG as the chemical accounting for a major portion of the aqueous solution (e.g., 50 wt%). High loading of TMG shifted the properties of water and enabled the dissolution of poorly water-soluble cisplatin, an anticancer agent, at high concentration (solubility of cisplatin: 0.15 wt% in watervs1.7 wt% in TMG aqueous solution). For hepatic arterial infusion, this can reduce the amount of cisplatin administered from 40 to 4 mL. It enables simple injection using a syringe, without the need for catheters and automatic pumps, leading to critical alleviation of the risk to patients. Furthermore, we produced a dry powder from a cisplatin-containing TMG aqueous solution via freeze-drying. Powders can be conveniently stored and transported. Furthermore, cisplatin is often used as a mixture with other drugs, and cisplatin aqueous solutions are not preferred as they dilute the other drugs.
Characteristics of soil salt crust formed by mixing calcium chloride with sodium sulfate and the possibility of inhibiting wind-sand flow
Authors: Li Shenghui , Li Chengzhi , Fu Xiaolei
Published: May 2021

Soil salt crust can change the structure of aeolian soil and improve its resistance to wind erosion. Four ions (Na+, Ca2+, Cl−, and SO42−) with high contents in aeolian soil were selected for a salt crust experiment. The experiment set a variety of gradients of soil salt contents and salt mixing ratios of Na2SO4 and CaCl2. The physical properties of the salt crust were tested, and the wind erosion resistance of the salt crust was discussed. The results showed that the soil salt contents and salt mixing ratio influenced the resistance of the salt crust, especially in terms of its compressive strength and toughness. The former affected the compressive strength of the salt crust by changing the amount of cemented soil salt. The latter affected the kinds of crystals by changing the ion ratio, thus changing the structure of the salt crust and affecting its wind erosion resistance. The wind erosion resistance of the salt crust is complicated by the interaction between the soil salt content and salt mixing ratio. A multilayer crust can be formed in mixed salt, which has a strong wind erosion resistance. This result provides new findings on flowing sand soil and a new method for the treatment of flowing sand soil.
Spotlight on PSMA as a new theranostic biomarker for bladder cancer
Authors: Tumedei Maria Maddalena , Ravaioli Sara , Matteucci Federica , Celli Monica , De Giorgi Ugo , Gunelli Roberta , Puccetti Maurizio , Paganelli Giovanni , Bravaccini Sara
Published: May 2021

Bladder cancer (BCa) patients are diagnosed by cytology and cystoscopy. However, these diagnostic tests bear some limitations. We sought for reliable biomarkers to better determine BCa extension. Prostate-specific membrane antigen (PSMA) appears to fulfill this requirement in prostate cancer but its role in BCa has not been established yet. We then analyzed 87 bladder tissue samples from 74 patients assessing PSMA expression by immunohistochemistry. The median PSMA expression, exclusively found in tumor neovasculature, in terms of H-score significantly differed between non-tumor samples and tumor samples (p = 0.00288) showing a higher neovasculature-related PSMA expression. No differences were observed in relation to tumor type, grade and stage. BCa neovasculature-related PSMA overexpression may be useful in defining the degree of extension of the neoplasm. In addition, testing PSMA expression by immunohistochemistry may hold theranostic implications both considering anti-angiogenesis agents and radio-labelled PSMA ligands for intracavitary radionuclide therapy. In our opinion, BCa neovasculature-related PSMA overexpression may be considered an apt target for anti-angiogenesis and radionuclide treatment in BCa, once the evaluation of tumor-retention time for the appropriateness of long half-life therapeutic PSMA ligands as radionuclide treatment will be performed.
Cold-induction of afadin in brown fat supports its thermogenic capacity
Authors: Lundh Morten , Altıntaş Ali , Tozzi Marco , Fabre Odile , Ma Tao , Shamsi Farnaz , Gerhart-Hines Zachary , Barrès Romain , Tseng Yu-Hua , Emanuelli Brice
Published: May 2021

The profound energy-expending nature of brown adipose tissue (BAT) thermogenesis makes it an attractive target tissue to combat obesity-associated metabolic disorders. While cold exposure is the strongest inducer of BAT activity, the temporal mechanisms tuning BAT adaptation during this activation process are incompletely understood. Here we show that the scaffold protein Afadin is dynamically regulated by cold in BAT, and participates in cold acclimation. Cold exposure acutely increases Afadin protein levels and its phosphorylation in BAT. Knockdown of Afadin in brown pre-adipocytes does not alter adipogenesis but restricts β3-adrenegic induction of thermogenic genes expression and HSL phosphorylation in mature brown adipocytes. Consistent with a defect in thermogenesis, an impaired cold tolerance was observed in fat-specific Afadin knockout mice. However, while Afadin depletion led to reduced Ucp1 mRNA induction by cold, stimulation of Ucp1 protein was conserved. Transcriptomic analysis revealed that fat-specific ablation of Afadin led to decreased functional enrichment of gene sets controlling essential metabolic functions at thermoneutrality in BAT, whereas it led to an altered reprogramming in response to cold, with enhanced enrichment of different pathways related to metabolism and remodeling. Collectively, we demonstrate a role for Afadin in supporting the adrenergic response in brown adipocytes and BAT function.
Low human dystrophin levels prevent cardiac electrophysiological and structural remodelling in a Duchenne mouse model
Authors: Marchal Gerard A. , van Putten Maaike , Verkerk Arie O. , Casini Simona , Putker Kayleigh , van Amersfoorth Shirley C. M. , Aartsma-Rus Annemieke , Lodder Elisabeth M. , Remme Carol Ann
Published: May 2021

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder caused by loss of dystrophin. This lack also affects cardiac structure and function, and cardiovascular complications are a major cause of death in DMD. Newly developed therapies partially restore dystrophin expression. It is unclear whether this will be sufficient to prevent or ameliorate cardiac involvement in DMD. We here establish the cardiac electrophysiological and structural phenotype in young (2–3 months) and aged (6–13 months) dystrophin-deficient mdx mice expressing 100% human dystrophin (hDMD), 0% human dystrophin (hDMDdel52-null) or low levels (~ 5%) of human dystrophin (hDMDdel52-low). Compared to hDMD, young and aged hDMDdel52-null mice displayed conduction slowing and repolarisation abnormalities, while only aged hDMDdel52-null mice displayed increased myocardial fibrosis. Moreover, ventricular cardiomyocytes from young hDMDdel52-null animals displayed decreased sodium current and action potential (AP) upstroke velocity, and prolonged AP duration at 20% and 50% of repolarisation. Hence, cardiac electrical remodelling in hDMDdel52-null mice preceded development of structural alterations. In contrast to hDMDdel52-null, hDMDdel52-low mice showed similar electrophysiological and structural characteristics as hDMD, indicating prevention of the cardiac DMD phenotype by low levels of human dystrophin. Our findings are potentially relevant for the development of therapeutic strategies aimed at restoring dystrophin expression in DMD.
Half-life modeling of basic fibroblast growth factor released from growth factor-eluting polyelectrolyte multilayers
Authors: Ding Ivan , Peterson Amy M.
Published: May 2021

Growth factor-eluting polymer systems have been widely reported to improve cell and tissue outcomes; however, measurements of actual growth factor concentration in cell culture conditions are limited. The problem is compounded by a lack of knowledge of growth factor half-lives, which impedes efforts to determine real-time growth factor concentrations. In this work, the half-life of basic fibroblast growth factor (FGF2) was determined using enzyme linked immunosorbent assay (ELISA). FGF2 release from polyelectrolyte multilayers (PEMs) was measured and the data was fit to a simple degradation model, allowing for the determination of FGF2 concentrations between 2 and 4 days of culture time. After the first hour, the FGF2 concentration for PEMs assembled at pH = 4 ranged from 2.67 ng/mL to 5.76 ng/mL, while for PEMs assembled at pH = 5, the concentration ranged from 0.62 ng/mL to 2.12 ng/mL. CRL-2352 fibroblasts were cultured on PEMs assembled at pH = 4 and pH = 5. After 2 days, the FGF2-eluting PEM conditions showed improved cell count and spreading. After 4 days, only the pH = 4 assembly condition had higher cells counts, while the PEM assembled at pH = 5 and PEM with no FGF2 showed increased spreading. Overall, the half-life model and cell culture study provide optimal concentration ranges for fibroblast proliferation and a framework for understanding how temporal FGF2 concentration may affect other cell types.
Response of the Indian summer monsoon to global warming, solar geoengineering and its termination
Authors: Bhowmick Mansi , Mishra Saroj Kanta , Kravitz Ben , Sahany Sandeep , Salunke Popat
Published: May 2021

The response of the Indian Summer Monsoon (ISM) to global warming, solar geoengineering and its termination is examined using the multi-model mean of seven global climate model simulations from G2 experiment of the Geoengineering Model Intercomparison Project. Under the global warming scenario, land–ocean temperature contrasts and low-level monsoon circulation progressively strengthen accompanied by enhanced precipitation over the Indian subcontinent. Notably, in the solar geoengineered scenario, marginal surface cooling is projected over the majority of the ISM region, and there is strengthening of both upper and lower level circulation. However, preferential precipitation near Western Ghats leads to dry bias over majority of Indian land. Upon the termination of the geoengineering, the climatic conditions—temperature, precipitation, winds and moisture would abruptly change to what it would have been under the global warming scenario. Thus, this may be important to note that such changes may need attention for the future mitigation and adaptation purposes if solar geoengineering is required to implement in future.
Identification of an optimal prolactin threshold to determine prolactinoma size using receiver operating characteristic analysis
Authors: Leca Bianca M. , Mytilinaiou Maria , Tsoli Marina , Epure Andreea , Aylwin Simon J. B. , Kaltsas Gregory , Randeva Harpal S. , Dimitriadis Georgios K.
Published: May 2021

Prolactinomas represent the most common type of secretory pituitary neoplasms, with a therapeutic management that varies considerably based on tumour size and degree of hyperprolactinemia. The aim of the current study was to evaluate the relationship between serum prolactin (PRL) concentrations and prolactinoma size, and to determine a cut-off PRL value that could differentiate micro- from macro-prolactinomas. A retrospective cohort study of 114 patients diagnosed with prolactinomas between 2007 and 2017 was conducted. All patients underwent gadolinium enhanced pituitary MRI and receiver operating characteristic (ROC) analyses were performed. 51.8% of patients in this study were men, with a mean age at the time of diagnosis of 42.32 ± 15.04 years. 48.2% of the total cohort were found to have microadenomas. Baseline serum PRL concentrations were strongly correlated to tumour dimension (r = 0.750, p = 0.001). When performing the ROC curve analysis, the area under the curve was 0.976, indicating an excellent accuracy of the diagnostic method. For a value of 204 μg/L (4338 mU/L), sensitivity and specificity were calculated at 0.932 and 0.891, respectively. When a cut off value of 204 μg/L (4338 mU/L) was used, specificity was 93.2%, and sensitivity 89.1%, acceptable to reliably differentiate between micro- and macro- adenomas.
Design aspects of vaginal applicators that influence acceptance among target users
Authors: Bakke Alyssa J. , Zaveri Toral , Higgins Molly J. , Ziegler Gregory R. , Hayes John E.
Published: May 2021

Although sensory-guided product design is most traditionally used by food and beverage companies, the approach has widespread application for many other products, including pharmaceuticals and medical devices. Previously, our team used sensory methods to explore preclinical optimization of soft-gel vaginal microbicides. Past clinical trials suggest vaginal microbicides may be an effective means for women to protect themselves from HIV and other sexually transmitted infections, but these microbicides will not work if they are not used due to poor acceptability. Our prior work suggests properties like firmness, size, and shape all influence women’s willingness to try soft-gel vaginal suppositories. As product insertion is part of the overall experience of using vaginal microbicides, understanding the features of vaginal applicators that appeal to women, and incorporating these insights into vaginal drug delivery systems, may also improve user adherence. Despite widespread use of vaginal applicators, there is minimal public data on women’s perceptions of and preferences for physical applicator features. Other work suggests women want vaginal applicators that are single use, pre-filled, made of plastic, and easy to use, store, and discard. Applicator attributes that may be important to women, such as length, color, or visual appeal, have not been investigated previously. The objective of this research was to understand what physical applicator attributes are appealing to women. Here, 18 commercially available applicators were evaluated by a convenience sample of women (n = 102) for overall liking and perceptions of various attributes (perceived length and width, ease-of-grip, expected ease-of-use, expected comfort inside the body, visual appeal, color liking, and environmental friendliness). Preference mapping using both liking data and attribute data showed attributes such as color, visual appeal, ease of grip, expected ease of use, and expected comfort inside the body drove higher liking ratings for applicators, while perceived length negatively affected liking. In general, plastic tampon applicators contained more positive features and were better liked relative to a cardboard tampon applicator or applicators for insertion of medicated gels or suppositories. Incorporating more desirable features into applicators meant for insertion of vaginal microbicides or other vaginal medications may improve the user experience, and possibly user adherence.
Evaluation of the performance and gas emissions of a tractor diesel engine using blended fuel diesel and biodiesel to determine the best loading stages
Authors: Emaish Haitham , Abualnaja Khamael M. , Kandil Essam E. , Abdelsalam Nader R.
Published: May 2021

Fossil fuels are the main energy sources responsible for harmful emissions and global warming. Using biodiesel made from waste deep-frying oil as an alternative fuel source in diesel engines has drawn great attention. This biodiesel is produced using the transesterification process and blends with mineral diesel at Faculty of Agriculture Saba Basha, Alexandria University, Egypt. The turbocharged diesel engine of a Kubota M-90 tractor was tested. The objectives of this work are to test tractor as a source of power in the farm using waste deep-frying oil biodiesel to utilize waste frying oils (WFO) in clean energy production on the farm and determine the best engine loading stages to maximize engine efficiencies for different fuel blends and reduce the environmental impact of gas emissions from tractor diesel engines in the farms. The experiment design was factorial, with two factors, where the first was the engine load (0%, 25%, 50%, 75%, and 100%) and the second was fuel blend (0%, 5%, 20%, and 100% biodiesel), and the effects of loading stages and biodiesel percentage on engine performance indicators of engine speed, power take off torque, power take off power, brake power, brake mean effective pressure, brake thermal efficiency, brake specific fuel consumption, and gas emissions were studied. The experimental results indicated that engine load percentage and fuel blend percentage significantly affected all studied characters, and the best engine loading stages were between 25 and 75% to maximize engine efficiency and minimize the specific fuel consumption and gas emissions. Increasing the biodiesel percentage at all loading stages resulted decreasing in Engine brake power (BP), brake thermal efficiency, Power take-off (PTO) torque, and brake mean effective pressure and increases in brake specific fuel consumption. Increasing the engine load resulted in decreases in O2 emissions and increases in CO2, CO, NO, and SO2 emissions. Increasing the biodiesel percentage in the blended fuel samples resulted in increases in O2 and NO emissions and decreases in CO2, CO, and SO2 emissions. The use of biodiesel with diesel fuel reduces the environmental impact of gas emissions and decreases engine efficiency.
Synthesis of Carbon Nanotube/Graphene Hybrids by Chemical Vapor Deposition
Authors: Liu Zhi , Li Hua-Fei , Deng Shuguang , Dai Gui-Ping
Published: May 2021

As a one-dimensional (1D) allotrope of carbon, carbon nanotubes (CNTs) have been widely investigated in the past two decades owing to their unique mechanical strength, large surface-to-volume ratio, and electrical properties. Graphene, a two-dimensional (2D) honeycomb nanostructure composed of single-layer carbon atoms, is also a promising choice for potential applications in energy storage. Interestingly, a fine combination of 1D and 2D building blocks that leads to the formation of a three-dimensional (3D) hierarchical structure could effectively inherit advantages of individual components and mitigate the aggregation and restacking of CNT and graphene, leading to unexpected properties for their outstanding application. Moreover, compared with other synthetic methods, the chemical vapor deposition (CVD) method is considered as a sophisticated approach for both laboratory research and industry production of nanocarbon materials or hybrids, and the carbon nanotube/graphene hybrids are expected to be a promising choice for high-performance applications in the future.
Design of Graphene/CNT-based Nanocomposites: A Stepping Stone for Energy-related Applications
Authors: Raza Waseem
Published: May 2021

The regular requirement for excellent, low weight, cost-effective, and durable materials have been the driving force for the investigation of novel materials. The exploration of carbon-based materials such as graphene has gained extensive research consideration due to its outstanding properties. Graphene is the thinnest (2D carbon) material in the universe with high charge carrier mobility, excellent chemical and mechanical stability, superb surface area, and good optical transparency. Therefore, it is expected to be an excellent and promising candidate in current material science research and nanotechnology. However, pristine graphene sheets are not suitable as flexible transparent conductors and many more applications due to the presence of defects, agglomeration behavior, and grain boundaries, while having high sheet resistance which can be broken easily and facing objection for designing controlled functionality. One decisive approach to explore the ability of graphene is to architect a graphene composite as a perfect building block for controllable functionalization with another carbon material with logical C–C junction formation. In this context, carbon nanotubes (CNTs) act as reinforcing bars that not only restrict the agglomeration behavior but also generate the synergistic effect between them as well as a bridge between different crystalline domains with outstanding chemical and physical properties. Therefore, this article aims to present readers with a better understanding of hybrid carbon design by creating covalent interconnection between CNT and graphene for energy-related applications.
One-dimensional Carbon Nanotube Decorated Two-dimensional Reduced Graphene Oxide Composite: Insight from Synthesis to Application in Dye Sensitized Solar Cells
Authors: Ahmad Khursheed , Mobin Shaikh M.
Published: May 2021

Carbonaceous materials such as carbon nanotubes and reduced graphene oxide have been widely applied in various optoelectronic applications. The carbon materials have high surface area and excellent electronic conductivity which makes them very promising materials for energy and other optoelectronic devices. The two-dimensional (2D) reduced graphene oxide which is an allotrope of carbon also has high hole transport mobility. In recent years, researchers have developed numerous strategies to prepare carbon nanotube decorated reduced graphene oxide composite for dye sensitized solar cell applications. Dye sensitized solar cells are photovoltaic devices which have the potential to convert sunlight into electricity. Dye sensitized solar cells are composed of different components such as a photoanode, light sensitizer, electrolyte and counter electrode. Generally, the counter electrode consists of platinum metal which is precious metal. Thus, carbonaceous materials as low-cost counter electrode materials have been employed for the construction of cost-effective and high-performance dye sensitized solar cells. Carbon nanotubes, reduced graphene oxide composites or carbon nanotube/reduced graphene oxide composites have been proven to be effective and highly efficient low-cost counter electrode materials for dye sensitized solar cells. In this chapter, we review the synthesis of carbon nanotube/reduced graphene oxide composites and their role as low-cost counter electrodes for the construction of dye sensitized solar cells.
Carbon Dot-based Composites: Recent Progress, Challenges and Future Outlook
Authors: Sim L. C. , Terng S. S. , Lim J. Y. , Ng J. J. , Chong W. C. , Leong K. H. , Saravanan P.
Published: May 2021

Carbon dots (CDs) have recently emerged as a promising cost-effective alternative to replace high-cost semiconductor quantum dots (QDs). There are three kinds of fluorescent CDs which are carbonized polymer dots (CPDs), carbon nanodots (CNDs), and graphene quantum dots (GQDs). Wide attention has been focused on CDs because of their characteristics such as water solubility, high biocompatibility, excellent photostability, low toxicity, and excitation wavelength dependent photoluminescence (PL) behavior. Moreover, the recent discovery of a multigram one-step synthesis of GQDs from coal or carbon sources opens the possibility of their large-scale industrial production. Although CPDs, CNDs and GQDs have similar quantum fluorescent carbon materials, they have different chemical and physical properties because of the differences in spatial arrangements of carbon atoms. This chapter aims to demonstrate the recent progress in the synthesis, properties and applications of CD-based composites in disease detection, optoelectronics, photovoltaics, hydrogen (H2) evolution, photocatalysis, etc. We also highlight the challenges and future direction of CD-based composites in this booming research field, with a perspective toward the ultimate achievement of highly efficient and long-term stable CD-based composites.
Clusters of Fullerenes
Authors: Hansen Klavs , Zettergren Henning
Published: May 2021

The structure and dynamics of clusters of the all-carbon fullerene molecules are reviewed. After a brief overview of the properties of the individual fullerene molecules, the experimentally determined structures and the theoretical interaction potentials describing the cluster properties are reviewed. The dynamics of fullerene–fullerene molecule interaction after exposure of clusters to laser excitation, in bi-molecular collisions and after exposure of clusters to high energy ion beams is then reviewed. These show that the end products may be (multiply) charged clusters, fragmented or intact fullerene monomers or a wide range of fusion products, depending on how the excitation energy is transferred to the clusters and the amount of it.
Less-common Carbon–Carbon Nanocomposites
Authors: Ibarra Torres Cynthia Estephanya , Kharissova Oxana V. , Oliva González Cesar Máximo , Kharisov Boris I.
Published: May 2021

It is well known that hybrid and composite materials exhibit improved properties in comparison with their individual components. Carbon–carbon materials have excellent thermal, mechanical and electrical properties. In this chapter, hybrids and compounds based on classic carbon nanostructures like CNTs and/or less common structures like nanospheres, nanoballs, or nanorings are reviewed. The main applications of these carbon–carbon materials include catalysis, energy storage, sensors, among others.
Advances in Polymeric Nanocomposites Incorporating Graphene–Fullerene and Graphene Oxide–Fullerene Hybrids
Authors: Kausar Ayesha
Published: May 2021

Graphene and fullerene are remarkable nanostructures that have received tremendous attention in recent decades. Both graphene and fullerene are nanocarbon structures. Linking of graphene and fullerene may be through physical or chemical interactions. Various theoretical, simulation, modeling, and practical studies have been performed on graphene–fullerene bi-nanostructures. The most important application of graphene–fullerene and graphene oxide–fullerene hybrids is as reinforcement in polymer matrices. Consequently, this chapter highlights several essential aspects of graphene–fullerene and graphene oxide–fullerene hybrids with special emphasis on polymer/graphene–fullerene and polymer/graphene oxide–fullerene nanocomposites. The hybrids based on two nanocarbons (graphene–fullerene) may act as marvelous nanobifillers and lead to synergistic effects in physical property enhancement. Dramatic improvements in nanocomposite features are due to the molecular level interactions between the matrices and the hybrids. However, the major challenges involved in the processing of these nanocomposites are the dispersion/solubility of the nanobifiller hybrid and the interfacial adhesion between the matrix and nanobifiller hybrid. These challenges can be overcome by forming the physically or covalently linked functional hybrid networks accountable for the improved physical properties of the nanocomposites. Finally, the practical and future prospects of the polymer/graphene–fullerene and the polymer/graphene oxide–fullerene nanocomposites have been summarized hoping to facilitate the progress in this emerging area of nanocomposite technology.
Observation and mechanism of cryo N2 cleavage by a tantalum cluster
Authors: Fries Daniela V. , Klein Matthias P. , Steiner Annika , Prosenc Marc H. , Niedner-Schatteburg Gereon
Published: May 2021

Twofold cryo N2 cleavage by Ta4+ clusters occurs via a multistep across edge-above surface (AEAS) mechanism across submerged barriers.
Optical, third order non-linear optical and electrochemical properties of dipolar, centrosymmetric andC2vorganoimido polyoxometalate derivatives
Authors: Al-Yasari Ahmed , El Moll Hani , Purdy Ryan , Vincent Kevin B. , Spence Philip , Malval Jean-Pierre , Fielden John
Published: May 2021

Arylimido Lindqvist polyoxometalates (POMs) are shown to be effective acceptors for two-photon absorption. In bis-POM systems the geometry–centrosymmetric or V-shaped–strongly influences optical and non-linear optical properties.
A new typology of human hair medullas based on lipid composition analysis by synchrotron FTIR microspectroscopy
Authors: Sandt Christophe , Borondics Ferenc
Published: May 2021

Chemical compositions of 130 human hair medullas were measured by synchrotron FTIR microscopy evidencing calcium carboxylates and unexpected chemical variability. Based on their lipid composition, human hair medullas were classified in 4 groups.