bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel frameshift mutation in PURA gene causes severe encephalopathy of unclear cause
Authors: Spangenberg Lucía , Guecaimburú Rosario , Tapié Alejandra , Vivas Susana , Rodríguez Soledad , Graña Martín , Naya Hugo , Raggio Víctor
Published: March 2021

Background

The etiology of many genetic diseases is challenging. This is especially true for developmental disorders of the central nervous system, since several genes can be involved. Many of such pathologies are considered rare diseases, since they affect less than 1 in 2000 people. Due to their low frequency, they present several difficulties for patients, from the delay in the diagnosis to the lack of treatments. Next‐generation sequencing techniques have improved the search for diagnosis in several pathologies. Many studies have shown that the use of whole‐exome/genome sequencing in rare Mendelian diseases has a diagnostic yield between 30% and 50% depending on the disease.

Methods

Here, we present the case of an undiagnosed 6‐year‐old boy with severe encephalopathy of unclear cause, whose etiological diagnosis was achieved by whole‐genome sequencing.

Results

We found a novel variant that has not been previously reported in patients nor it has been described in GnomAD. Segregation analysis supports a de novo mutation, since it is not present in healthy parents. The change is predicted to be harmful to protein function, since it falls in the first quarter of the protein producing an altered reading frame and generating a premature stop codon. Additionally, the variant is classified as pathogenic according to ACMG criteria (PVS1, PM2, and PP3). Furthermore, there are several reported frameshift mutations in nearby codons as well as nonsense mutations that are predicted as pathogenic in other studies.

Conclusion

We found a novel de novo frameshift mutation in the PURA gene (MIM number 600473), c.151_161del, with sufficient evidence of its pathogenicity.
A new method for solving variable coefficients fractional differential equations based on a hybrid of Bernoulli polynomials and block pulse functions
Authors: Zhang Bo , Tang Yinggan , Zhang Xuguang
Published: March 2021

Block pulse functions (BPFs) are constant functions on each subinterval and not so smooth. This property makes BPFs incapable of approximating function accurately. Therefore, the existing BPFs method is insufficiently accurate to numerically solve variable coefficients fractional differential equations (VCFDEs). To obtain highly accurate solutions with fewer computational burden, we propose an efficient numerical method to find the approximate solutions of VCFDEs. The proposed method uses a hybrid of Bernoulli polynomials and BPFs (HBPBPFs) to overcome the disadvantage that BPFs are piecewise constant and smooth enough. For this aim, a fractional integral operational matrix of HBPBPFs is derived and used to convert VCFDEs into a system of algebraic equations. The solutions of VCFDEs are obtained by solving the algebraic equations. Some simulation examples are presented to verify the effectiveness of our proposed method. Numerical results from our proposed method are compared with those from the existing BPFs numerical method. It is demonstrated that our method can obtain more accurate approximate solutions than the BPFs method.
Calibration‐free regional RF shims for MRS
Authors: Berrington Adam , Považan Michal , Mirfin Christopher , Bawden Stephen , Park Young Woo , Marsh Daniel C. , Bowtell Richard , Gowland Penny A.
Published: March 2021

Purpose

Achieving a desired RF transmit field () in small regions of interest is critical for single‐voxel MRS at ultrahigh field. Radio‐frequency (RF) shimming, using parallel transmission, requires mapping and optimization, which limits its ease of use. This work aimed to generate calibration‐free RF shims for predefined target regions of interest, which can be applied to any participant, to produce a desired absolute magnitude (||).

Methods

The RF shims were found offline by joint optimization on a database comprising maps from 11 subjects, considering regions of interest in occipital cortex, hippocampus and posterior cingulate, as well as whole brain. The || achieved was compared with a tailored shimming approach, and MR spectra were acquired using tailored and calibration‐free shims in 4 participants. Global and local 10g specific‐absorption‐rate deposition were estimated using Duke and Ella dielectric models.

Results

There was no difference in the mean || produced using calibration‐free versus tailored RF shimming in the occipital cortex (p = .15), hippocampus (p = .5), or posterior cingulate (p = .98), although differences were observed in the RMS error ||. Spectra acquired using calibration‐free shims had similar SNR and low residual water signal. Under identical power settings, specific‐absorption‐rate deposition was lower compared with operating in quadrature mode. For example, the total head specific absorption rate was around 35% less for the occipital cortex.

Conclusion

This work demonstrates that static RF shims, optimized offline for small regions, avoid the need for mapping and optimization for each region of interest and participant. Furthermore, power settings may be increased when using calibration‐free shims, to better take advantage of RF shimming.
Dynamic MRI of the abdomen using parallel non‐Cartesian convolutional recurrent neural networks
Authors: Zhang Yufei , She Huajun , Du Yiping P.
Published: March 2021

Purpose

To improve the image quality and reduce computational time for the reconstruction of undersampled non‐Cartesian abdominal dynamic parallel MR data using the deep learning approach.

Methods

An algorithm of parallel non‐Cartesian convolutional recurrent neural networks (PNCRNNs) was developed to enable the use of the redundant information in both spatial and temporal domains, and achieve data fidelity for the reconstruction of non‐Cartesian parallel MR data. The performance of PNCRNNs was evaluated for various acceleration rates, motion patterns, and imaging applications in comparison with that of the state‐of‐the‐art algorithms of dynamic imaging, including extra‐dimensional golden‐angle radial sparse parallel MRI (XD‐GRASP), low‐rank plus sparse matrix decomposition (L+S), blind compressive sensing (BCS), and 3D convolutional neural networks (3D CNNs).

Results

PNCRNNs increased the peak SNR of 9.07 dB compared with XD‐GRASP, 9.26 dB compared with L+S, 3.48 dB compared with BCS, and 3.14 dB compared with 3D CNN at R = 16. The reconstruction time was 18 ms for each bin, which was two orders faster than that of XD‐GRASP, L+S, and BCS. PNCRNNs provided good reconstruction for various motion patterns, k‐space trajectories, and imaging applications.

Conclusion

The proposed PNCRNN provides substantial improvement of the image quality for dynamic golden‐angle radial imaging of the abdomen in comparison with XD‐GRASP, L+S, BCS, and 3D CNN. The reconstruction time of PNCRNN can be as fast as 50 bins per second, due to the use of the highly computational efficient Toeplitz approach.
Improved method for post‐processing correction of B1 inhomogeneity in glutamate‐weighted CEST images of the human brain
Authors: Cember Abigail T. J. , Hariharan Hari , Kumar Dushyant , Nanga Ravi P. R. , Reddy Ravinder
Published: March 2021

Glutamate‐weighted CEST (gluCEST) imaging is nearly unique in its ability to provide non‐invasive, spatially resolved measurements of glutamate in vivo. In this article, we present an improved correction for B1 inhomogeneity of gluCEST images of the human brain. Images were obtained on a Siemens 7.0 T Terra outfitted with a single‐volume transmit/32‐channel receive phased array head coil. Numerical Bloch‐McConnell simulations, fitting and data processing were performed using in‐house code written in MATLAB and MEX (MATLAB executable). “Calibration” gluCEST data was acquired and fit with a phenomenological functional form first described here. The resulting surfaces were used to correct experimental data in accordance with a newly developed method. Healthy volunteers of varying ages were used for both fitted “calibration” data and corrected “experimental” data. Simulations allowed us to describe the dependence of CEST at 3.0 ppm (gluCEST) on saturation B1 using a new functional form, whose validity was confirmed by successful fitting to real human data. This functional form was used to parameterize surfaces over the space (B1, T1), which could then be used to correct the signal from each pixel. The resulting images show less signal loss in areas of low B1 and greater contrast than those generated using the previously published method. We demonstrate that, using this method with appropriate nominal saturation B1, the major limitation of correcting for B1 inhomogeneity becomes the effective flip angle of the acquisition module, rather than inability to correct for inhomogeneous saturation. The lower limit of our correction ability with respect to both saturation and acquisition B1 is about 40% of the nominal value. In summary, we demonstrate a more rigorous and successful approach to correcting gluCEST images for B1 inhomogeneity. Limitations of the method and further improvements to enable correction in regions with severe pathology are discussed.
Accelerated long‐term forgetting is a BACE1 inhibitor‐reversible incipient cognitive phenotype in Alzheimer’s disease model mice
Authors: Ohno Masuo
Published: March 2021

Aim

After the continued failure of β‐secretase (BACE1) inhibitor clinical trials in prodromal as well as mild‐to‐moderate Alzheimer's disease (AD), they are shifting to further earlier or asymptomatic stages. The aim of this study is to explore a cognitive paradigm that allows us to more sensitively detect beneficial effects of BACE1 inhibitors in presymptomatic AD.

Methods

GRL‐8234 (33.4 mg/kg, ip), a small‐molecule BACE1 inhibitor, was administered once daily for 28 days to the 5XAFD transgenic mouse model of AD. The contextual fear conditioning was used to evaluate the effects of GRL‐8234 on memory deficits in 5XFAD mice at different ages.

Results

Chronic administration of GRL‐8234 to 5XFAD mice rescued their contextual memory deficits, when tested 1 day after training at 6‐8 months but not at 12 months of age. Importantly, 4‐month‐old 5XFAD mice retain the ability to form contextual memory equivalent to wild‐type controls, demonstrating that the standard method of 1‐day memory assessment is not suitable for evaluating BACE1 inhibitor efficacy in ameliorating cognitive declines during earlier disease stages. Despite normal contextual memory formation, young 5XFAD mice showed faster forgetting when a longer delay (28 days) intervened between training and memory testing. Notably, GRL‐8234 administered to 4‐month‐old 5XFAD mice during the 28‐day delay reversed accelerated long‐term forgetting almost completely back to wild‐type control levels.

Conclusion

The results provide experimental evidence that accelerated long‐term forgetting represents more sensitive memory testing that can help evaluate BACE1 inhibitor therapy in presymptomatic AD populations.
Covid‐19 pandemic: Challenges and ways forward for the Indian microfinance institutions
Authors: Sangwan Sunil , Nayak Narayan Chandra , Sangwan Vikas , Pradhan Ashis Kumar
Published: March 2021

To contain the spread of the Covid‐19 pandemic, the mandated social distancing and restricted market activities have adversely affected the employment and earnings of the poor who are considered the targeted beneficiaries of the Microfinance Institutions (MFIs). The MFI operation and more specifically fresh lending are under serious threat as the mode of operations primarily involve physical interaction while distributing credits at the clients' doorsteps, conducting periodic group meetings and carrying out regular collections. This short article attempts to analyze the various challenges that MFIs may encounter in their current and future operations due to the ongoing pandemic. It discusses how the government initiated coping mechanisms may help MFIs overcome or minimize the pandemic challenges. At the same time, MFIs' efforts towards continued services are expected to create a win‐win situation.
RETRACTED: Principles of the Ukrainian social welfare system in the context of European integration
Authors: Gnatenko Karina V. , Vapnyarchuk Natalya M. , Vetukhova Irina A. , Yakovleva Galina O. , Sydorenko Anna S.
Published: March 2021

At the stage of the development of a new social welfare system in Ukraine, it is important to investigate all possible models and develop recommendations for the implementation of the most effective ones. The relevance of this paper lies in the study of the legal framework that operates in Ukraine and the possibilities of its improvement and consolidation into a more specific regulation. The purpose of the research was to study the principles of the social welfare system in Ukraine and to study foreign practices of the social welfare system. Within the framework of this study, the existing systems and models of social welfare systems in different countries were analyzed. The study identifies the most positive examples of social welfare policy for implementation in the current legal framework to improve and enhance the quality of social services in Ukraine. The analyzed foreign practices helped to identify the most effective models of social security. It was concluded that with the successful redistribution of funds, the introduction of a system of audit and control of social assistance financing, as well as being guided by foreign experience, Ukraine will be able to build a social welfare system that would satisfy all of the existing social needs of citizens.
Public administration, context and innovation: A framework of analysis
Authors: Ongaro Edoardo , Gong Ting , Jing Yijia
Published: March 2021

Innovation in public administration (PA) has played a pivotal role in building good governance and has attracted significant attention in the academia. The literature on PA innovation is burgeoning; however, this article argues that there is ‘a missing link’ in the extant literature in that the impacts of variation in context on PA innovation have not been sufficiently investigated. This article elaborates the analytical perspectives on the influences of various contexts over PA innovation and the mechanisms through which impacts may take place. Both theoretical and methodological complexities and challenges are apparent in disentangling contextual influences from other factors. The article proposes a research agenda for a context‐orientated comparative analysis of PA innovation and offers a brief illustration regarding contextual differences between China and the European Union in existing studies. The article calls for further studies in this direction.
Advancing drug discovery using the power of the human genome
Authors: Heilbron Karl , Mozaffari Sahar V , Vacic Vladimir , Yue Peng , Wang Wei , Shi Jingchunzi , Jubb Adrian M , Pitts Steven J , Wang Xin
Published: March 2021

Human genetics plays an increasingly important role in drug development and population health. Here we review the history of human genetics in the context of accelerating the discovery of therapies, present examples of how human genetics evidence supports successful drug targets, and discuss how polygenic risk scores could be beneficial in various clinical settings. We highlight the value of direct‐to‐consumer platforms in the era of fast‐paced big data biotechnology, and how diverse genetic and health data can benefit society. © 2021 23andMe, Inc. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Origins and mechanisms leading to aneuploidy in human eggs
Authors: Wartosch Lena , Schindler Karen , Schuh Melina , Gruhn Jennifer R. , Hoffmann Eva R. , McCoy Rajiv C. , Xing Jinchuan
Published: March 2021

The gain or loss of a chromosome—or aneuploidy—acts as one of the major triggers for infertility and pregnancy loss in humans. These chromosomal abnormalities affect more than 40% of eggs in women at both ends of the age spectrum, that is, young girls as well as women of advancing maternal age. Recent studies in human oocytes and embryos using genomics, cytogenetics, and in silico modeling all provide new insight into the rates and potential genetic and cellular factors associated with aneuploidy at varying stages of development. Here, we review recent studies that are shedding light on potential molecular mechanisms of chromosome missegregation in oocytes and embryos across the entire female reproductive life span.
Intranasal glial heterotopia in an infant boy
Authors: Zhang Wei , Tang Lixing , Ge Wentong
Published: March 2021

Introduction

Nasal glial heterotopia is a rare congenital developmental disorder characterized by meningeal epithelium and/or glial components.

Case presentation

A 2‐month‐old boy presented for treatment of a congenital mass in the right nasal cavity near the pharynx. The preoperative diagnosis was congenital intranasal neoplasm. Nasal endoscopic resection of the nasopharyngeal mass was performed under general anesthesia. Histological findings in the resected tissue supported a diagnosis of intranasal glial heterotopia. The surgical outcome was good and no surgical site infection occurred. During 1 year of follow‐up, the patient did not exhibit recurrence of heterotopia or related symptoms.

Conclusion

Transnasal endoscopic surgery is recommended for patients with intranasal glial heterotopia. Thorough preoperative imaging should be performed before glioma resection. The mass should be differentiated from encephalocele to prevent cerebrospinal fluid leakage and meningitis.
Neurodevelopmental outcomes of infants with bronchopulmonary dysplasia
Authors: DeMauro Sara B.
Published: March 2021

Preterm infants with bronchopulmonary dysplasia (BPD), and particularly those who develop the most severe forms of chronic lung disease during the neonatal period, are at high risk for poor developmental outcomes throughout childhood. Infants who require mechanical ventilation at 36 weeks post‐menstrual age have significantly increased odds for cerebral palsy, developmental delay at 2 years, and poor academic achievement and low intelligence quotient in adolescence. Over the past several decades, many therapies and care strategies, including steroids, continuous positive airway pressure, surfactant, and other medications have been introduced into clinical practice. These approaches have changed the epidemiology of BPD in very preterm infants. However, BPD remains common and strongly associated with poor development throughout childhood. Only caffeine has been proven to reduce BPD and improve childhood developmental outcomes. In future research, it will be essential to better understand the developmental sequelae of BPD beyond school age and to test interventions to improve developmental trajectories in this population. As new management strategies for BPD are developed, it will be essential to rigorously evaluate both short‐term and long‐term effects before they are introduced into routine neonatal practice.
Catalyst Free Single Step Specific Determination of Hydrazine in UH 25 blend and Determination of Propellant Grade UH 25 blend Using Thiophenes with Active Carbonyl Groups
Authors: Selvakumar S. , Reddy K. Audisesha , Munirathinam B.
Published: March 2021

Hydrazine and its derivatives such as monomethyl hydrazine (MMH), unsymmetrical dimethyl hydrazine (UDMH), and UH25 (a blend of 75 % UDMH and 25 % hydrazine hydrate by w/w) namely hydrazines are used as fuels (in liquid form) for rocket stages and satellites. They are hypergolic and well‐known toxic compounds. Workplace atmospheres involving vapours / liquid forms of these hydrazines need to be routinely monitored and screened. Simple, economical, and rapid kinetic spectrophotometric techniques are developed to meet the requirements by using thiophene‐3‐carboxaldehyde and 3‐butenone (E)‐1,1,1‐trifluoro‐4‐(3‐thienyl) (CF3enone) and compared. Classical −CHO based technique is applied for UH25 blend (in aqueous medium) in the presence of an acid catalyst. CF3enone based technique is used to determine hydrazine (Hz) in UH25 (in organic medium) selectively at levels as low as 0.05 mM without any catalyst. Variables such as temperature and concentration are optimized to determine UH25 in the concentration range of 0.5 mM to 0.1 M for thiophene‐3‐carboxaldehyde and to determine Hz of UH25 blend in the concentration range of 0.1 mM to 0.6 mM for CF3enone. Minimum detectable limits are found for UH25 and Hz of UH25 blend in the respective studies. GC‐MS study is also carried out to meet the unequivocal identification requirement. Initial rate and fixed time methods are adopted as calibration procedures. Orders of the reactions are found in both studies. Both techniques are simple and rapid after the chemisorption process with derivatizing agents in which pre‐treatment, pre‐concentration, and extraction steps are not involved. Advantages of CF3enone based technique over aldehyde‐based classical technique are 1) requirement of the minimum concentration of derivatizing agent 2) no catalyst 3) selectivity and specificity towards hydrazine in UH25 blend 4) shortened analysis time 5) linear dynamic range at very low concentrations of UH25.
Experimental Investigation and Modeling the Compressive Behavior of NEPE Propellant under Confining Pressure
Authors: Li Hui , Xu Jin‐sheng , Chen Xiong , Hou Yu‐fei , Fan Xing‐gui , Li Meng , Li Hong‐wen
Published: March 2021

In order to study the effects of confining pressure and strain rate on the mechanical properties of the Nitrate Ester Plasticized Polyether (NEPE) propellant, compressive tests were conducted under various confining pressure conditions and strain rates using a new‐designed active gas confining pressure testing machine. The stress‐strain curves and mechanical properties of the NEPE propellant under varying confining pressure conditions and strain rates were obtained. The results show that the compressive mechanical properties of the NEPE propellant are remarkably influenced by the confining pressure and strain rate. The compressive strength under confining pressure is obviously larger than those without applied confining pressure. With the coupled effects of the confining pressure and strain rate, the compressive strength under 5.4 MPa and 6.67×10−2 s−1 is 2.17 times of its value at room condition and 6.67×10−4 s−1. Then, based on previous tensile results, the quantified comparisons of tensile and compressive mechanical properties under different experimental conditions were presented. Finally, a nonlinear constitutive model with damage was constructed to model the effect of pressure. The statistical damage model parameters were defined as ExpDec1 function of pressure P. The calibrated model can accurately predict the mechanical behaviour of the NEPE propellant under different confining pressure conditions and strain rates.
In vitro cytochrome P450‐ and transporter‐mediated drug interaction potential of 6β‐hydroxy‐21‐desacetyl deflazacort—A major human metabolite of deflazacort
Authors: Ma Jiyuan , Beers Brian , Manohar Ravi , Roe Stephen , Colacino Joseph M. , Kong Ronald
Published: March 2021

6β‐Hydroxy‐21‐desacetyl deflazacort (6β‐OH‐21‐desDFZ) is a major circulating but not biologically active metabolite of deflazacort (DFZ). In vitro studies were performed to evaluate cytochrome P450 (CYP)‐ and transporter‐mediated drug interaction potentials of 6β‐OH‐21‐desDFZ. Up to 50 µM, the highest soluble concentration in the test system, 6β‐OH‐21‐desDFZ weakly inhibited (IC50 > 50 µM) the enzyme activity of CYPs 1A2, 2B6, 2C8, 2C9, and 2D6, while moderately inhibiting CYP2C19 and CYP3A4 with IC50 values of approximately 50 and 35 μM, respectively. The inhibition was neither time‐dependent nor metabolism‐based. Incubation of up to 50 µM 6β‐OH‐21‐desDFZ with plated cryopreserved human hepatocytes for 48 h resulted in no meaningful concentration‐dependent induction of either mRNA levels or enzyme activity of CYP1A2, CYP2B6, or CYP3A4. In transporter inhibition assays, 6β‐OH‐21‐desDFZ, up to 50 µM, did not show interaction with human OAT1, OAT3, and OCT2 transporters. It weakly inhibited (IC50 > 50 µM) human MATE1, MATE2‐K, and OCT1 transporter activity, and moderately inhibited human MDR1, OATP1B1, and OATP1B3 transporter activity with IC50 values of 19.81 μM, 37.62 μM, and 42.22 μM, respectively. 14C‐6β‐OH‐21‐desDFZ was biosynthesized using bacterial biotransformation and the subsequent study showed that 6β‐OH‐21‐desDFZ was not a substrate for human BCRP, MDR1, MATE1, MATE2‐K, OAT1, OATP1B1, OATP1B3, and OCT2 transporters, but appeared to be an in vitro substrate for the human OAT3 uptake transporter. At plasma concentrations of 6β‐OH‐21‐desDFZ seen in the clinic, CYP‐ and transporter‐mediated drug–drug interactions are not expected following administration of a therapeutic dose of DFZ in Duchenne muscular dystrophy (DMD) patients.
The prevalence of celiac disease in women with infertility—A systematic review with meta‐analysis
Authors: Glimberg Ida , Haggård Linnea , Lebwohl Benjamin , Green Peter H. R. , Ludvigsson Jonas F.
Published: March 2021

Purpose

To determine the prevalence of celiac disease in infertile women.

Methods

A systematic search of four databases was conducted up until February 6, 2020. The search terms “c(o)eliac disease”, “gluten”, “vill(o)us atrophy”, “infertility” and “subfertility” yielded 1142 unique hits. Articles in other languages than English, conference abstracts, letters, and publications where relevant information was missing were excluded. In our main analysis, celiac disease had to be verified by duodenal biopsy. The titles and abstracts, and the full‐text articles were independently reviewed by two researchers. A fixed‐effect model was used to calculate the weighted prevalence.

Results

Based on 11 studies (1617 women), the pooled prevalence of biopsy‐confirmed celiac disease was 0.7% (95% CI = 0.2%‐1.2%) in women with any infertility. Restricting our study population to women with unexplained infertility, the pooled prevalence of biopsy‐confirmed celiac disease was 0.6% (95% CI = 0.0%‐1.6%). When including studies where celiac disease had been defined per serology (20 studies; 5158 women), the pooled prevalence of celiac disease was 1.1% (95% CI = 0.6%‐1.6%) in women with any infertility.

Conclusion

Our results indicate that celiac disease is not more common in infertile women than in the general population. Celiac screening in infertile women may have low yield.
Address the rise in contract cheating amid the virtual learning environment
Authors: McCarthy Claudine
Published: March 2021

While virtual tools have allowed students to continue learning during the pandemic, the remote environment has also increased contract cheating. To help you hold your students accountable and address the source of the problem with online vendors, student conduct professionals from the University of Washington shared their lessons learned during the Association for Student Conduct Administration's annual conference, held virtually in February.
Ferulic Acid Promotes Bone Defect Repair After Radiation by Maintaining the Stemness of Skeletal Stem Cells
Authors: Liang Jia-Wu , Li Pei-Lin , Wang Qian , Liao Song , Hu Wei , Zhao Zhi-Dong , Li Zhi-Ling , Yin Bo-Feng , Mao Ning , Ding Li , Zhu Heng
Published: March 2021

The reconstruction of irradiated bone defects after settlement of skeletal tumors remains a significant challenge in clinical applications. In this study, we explored radiation-induced skeletal stem cell (SSC) stemness impairments and rescuing effects of ferulic acid (FA) on SSCs in vitro and in vivo. The immunophenotype, cell renewal, cell proliferation, and differentiation of SSCs in vitro after irradiation were investigated. Mechanistically, the changes in tissue regeneration-associated gene expression and MAPK pathway activation in irradiated SSCs were evaluated. The regenerative capacity of SSCs in the presence of FA in an irradiated bone defect mouse model was also investigated. We found that irradiation reduced CD140a- and CD105-positive cells in skeletal tissues and mouse-derived SSCs. Additionally, irradiation suppressed cell proliferation, colony formation, and osteogenic differentiation of SSCs. The RNA-Seq results showed that tissue regeneration-associated gene expression decreased, and the Western blotting results demonstrated the suppression of phosphorylated p38/MAPK and ERK/MAPK in irradiated SSCs. Notably, FA significantly rescued the radiation-induced impairment of SSCs by activating the p38/MAPK and ERK/MAPK pathways. Moreover, the results of imaging and pathological analyses demonstrated that FA enhanced the bone repair effects of SSCs in an irradiated bone defect mouse model substantially. Importantly, inhibition of the p38/MAPK and ERK/MAPK pathways in SSCs by specific chemical inhibitors partially abolished the promotive effect of FA on SSC-mediated bone regeneration. In summary, our findings reveal a novel function of FA in repairing irradiated bone defects by maintaining SSC stemness and suggest that the p38/MAPK and ERK/MAPK pathways contribute to SSC-mediated tissue regeneration postradiation.
Blood glucose‐lowering effect of water and ethanolic extracts of Gynura procumbens (Lour.) Merr
Authors: Aung Cho L. , Kawakami Fumitaka , Imai Motoki , Lwin Thet‐Thet , Kanzaki Makoto , Mar Ohn , Phyu Khin P. , Thwin Mya M. , Maruyama Hiroko
Published: March 2021

Aim

Gynura procumbens (Lour.) Merr. (GP) has drawn attention as an alternative drug for the treatment of diabetes mellitus. However, while most previous studies were done in diabetic mice to investigate the antidiabetic effect, this study investigated the blood glucose‐lowering action of GP in diet‐induced obese mice and clarified the possible mechanism of the glucose‐lowering action of GP in muscle and adipose cells.

Methods

The mice were divided into four groups (n = 6 in each group) depending on the diet that they received (i.e., the normal diet (ND), normal diet + 1% GP powder (ND + GP), high‐fat diet (HFD), high‐fat diet + 1% GP powder (HFD + GP) groups), and the oral glucose tolerance test (OGTT) was performed after one, three and five months. Immunocytochemistry revealed GLUT4 translocation in cells stably expressing myc‐GLUT4‐ECFP. The effect of GP extracts on the expression of GLUT4 and phosphorylation of 5'‐adenosine monophosphate‐activated protein kinase (AMPK) and Akt/protein kinase B (PKB) in C2C12 (muscle cell) and 3T3‐L1 (adipocyte) cells, was determined by western blot analysis.

Results

The results showed that the significantly raised serum glucose levels in the HFD group were reduced following treatment with GP powder. Moreover, treatment with the GP extracts promoted GLUT4 membrane translocation more prominently in the C2C12 cells as compared to the 3T3‐L1 cells, whereas GLUT4 expression was significantly increased only in the 3T3‐L1 cells. AMPK phosphorylation was significantly increased by both extracts in both C2C12 cells and 3T3‐L1 cells.

Conclusion

The findings of the present study reveal that GP may correct glucose intolerance and both the ethanolic and water extracts of GP have a blood glucose‐lowering effect, possibly via AMPK‐mediated signaling pathways in the muscle and adipose tissues.
Panax ginseng modulates oxidative stress, DNA damage, apoptosis, and inflammations induced by silicon dioxide nanoparticles in rats
Authors: El‐Demerdash Fatma M. , El‐Magd Mohammed A. , El‐Sayed Raghda A.
Published: March 2021

Silicon dioxide nanoparticles (SiO2NPs) are extensively used in cosmetics, food, and drug delivery. The main mechanism of SiO2NPs toxicities depends on oxidative stress. Ginseng (Panax ginseng Meyer) is used in various medicinal applications because of its antioxidant efficiency. Therefore, the present study was carried out to investigate the possible combated role of ginseng against SiO2NPs toxicity in rat liver. Thirty‐five male rats (160–180 g) were allocated into five groups of seven rats each, randomly. The first group was used as a control while groups 2, 3, 4, and 5 were treated orally with ginseng (Gin; 75 mg/kg, 1/10 LD50), SiO2NPs, (200 mg/kg, 1/10 LD50), Gin + SiO2NPs (protection group), and SiO2NPs + Gin (therapeutic group) for 5 weeks, respectively. Treatment with SiO2NPs increased lipid peroxidation, liver function enzymes, and decreased antioxidant enzymes (SOD, CAT, GPx, GST) activity and non‐enzymatic antioxidant (GSH) level. SiO2NPs administration motivated liver apoptosis as revealed by the upregulation of the apoptotic genes, Bcl2‐associated x protein (Bax), and Beclin 1 and downregulation of the anti‐apoptotic gene, B‐cell lymphoma 2 (Bcl2) as well as increase in DNA damage. Also, SiO2NPs administration caused inflammation as indicated by upregulation of the inflammation‐related genes (interleukin 1 beta [IL1β], tumor necrosis factor‐alpha [TNFα], nuclear factor kappa B [NFκB], cyclooxygenase 2 [Cox2], transforming growth factor‐beta 1 [TGFβ1]) as well as cell cycle arrest in the G0/G1 phase of liver cells. Moreover, histopathological examination proved the biochemical and molecular perturbations occurred due to SiO2NPs toxicity. On the other hand, ginseng caused a significant modulation on the deleterious effects induced by SiO2NPs in rat liver. In conclusion, ginseng has a potent preventive effect than the therapeutic one and might be used in the treatment of SiO2NPs hepatotoxicity.
The inventory of camel feed resource and the evaluation of its chemical composition in south‐east rangelands of Ethiopia
Authors: Habte Matiwos , Eshetu Mitiku , Andualem Dereje , Maryo Melesse , Legesse Abiyot
Published: March 2021

Background

Evaluations of available camel feed nutritive value are relevant to generate evidence on further camel feed improvements and find out the components to be supplemented.

Objective

This study aim to evaluate seasonal variations on chemical composition of selected camel feed in semi‐arid regions of south‐east Ethiopia.

Methods

Samples of edible portions from 15 browse species were collected during the dry and wet seasons, and their chemical compositions were analysed.

Results

The crude protein (CP), in vitro dry matter digestibility (IVDMD) and relative feed value (RFV) of evaluated browse species were higher (p < .01) in wet season than the dry season except for Acacia asak, Ipomoea donaldsonii and Acacia mellifera. Nonetheless, the neutral detergent fibre (NDF) and acid detergent fibre (ADF) contents were higher (p < .01) in the dry season except for A. asak and I. donaldsonii. Moreover, A. asak, I. donaldsonii and A. mellifera were the browse species with higher (p < .01) RFV, IVDMD and CP but lower NDF and ADF during the dry season than the wet season, and these species are qualified as good‐quality forage. Thus. Barleria spinisepala were better to use in both seasons, but browse species like I. donaldsonii and A. asak in dry season were ranked as best quality roughage.

Conclusion

At richest level on vital components (CP and fibres), these species can serve as well ruminant diets, like for camel. Further investigations based on animal trials are needed in order to confirm the classification standards of feed quality used in this study.
Influence Of Lithium Coordinating Additives On The Structure Of Phenyldimethylsilyllithium
Authors: Achternbosch Moritz , Brieger Lukas , Strohmann Carsten
Published: March 2021

The synthesis and structural investigation of two dimethylphenylsilyllithium adducts with coordinating nitrogen donors quinuclidine and 1,3,5‐tri‐tert‐butylhexahydro‐1,3,5‐triazine (tbtac) are presented. The structures show a comparatively long Si−Li distance and one amongst the shortest in monomeric silyllithiums reported so far, respectively. The structural investigations shed light on the influence of the donating additive for the lithium center on the structure of silyllithium compounds.
Quantum Algorithms
Authors: Hughes Ciaran , Isaacson Joshua , Perry Anastasia , Sun Ranbel F. , Turner Jessica
Published: March 2021

We have come a long way from Chap. 10.1007/978-3-030-61601-4_1 To recap on what we have learnt, we have understood important quantum mechanical phenomena such as superposition and measurement (through the Stern-Gerlach and Mach-Zehnder experiments). We have also learnt that while quantum computers can in principle break classical encryption protocols, they can also be used to make new secure channels of communication. Furthermore, we have applied quantum logic gates to qubits to perform quantum computations. With entanglement, we teleported the information in an unknown qubit to another qubit. This is quite a substantial achievement.
Being a ‘Good Researcher’ in Transdisciplinary Research: Choreographies of Identity Work Beyond Community
Authors: Schikowitz Andrea
Published: March 2021

Different contemporary developments are challenging the notion of a rather exclusive and lasting belonging of individual researchers to the one disciplinary community into which they had been socialised, to which they subsequently contribute, and which they reproduce. In turn, the very meaning of community is challenged when there is a perpetual exchange of community members. This chapter deals with how researchers with diverse and dynamic relations to different collectives develop a self-understanding of what it means to be a good researcher, i.e. what the normative ideals are that they should strive for. It is empirically analysed how researchers who engage in transdisciplinary research occasionally or regularly narrate, adopt, translate, resist, and combine the different imaginations of being a good researcher that they encounter. The sensitizing concept of ‘choreography’ is proposed to analyse the identity work done under conditions of multiple and flexible belongings that is held together by a certain style, rhythm, and pattern. In this sense, a specific way of moving constitutes an identity in the first place by aligning otherwise separate belongings.
The Emergence of Technoscientific Fields and the New Political Sociology of Science
Authors: Raimbault Benjamin , Joly Pierre-Benoît
Published: March 2021

This chapter conceptualizes the emergence of a techno-scientific field (TSF) as a multiscalar and progressive establishment of a new set of epistemic and social rules. Drawing on science and technology studies and field theories, we design an original conceptual framework that allows us to formulate three propositions to characterize the process of emergence of a TSF. We use the emergence of synthetic biology (Synbio) as a ‘laboratory’ to test this framework. Each proposition refers to a determinant dimension in the process of emergence—heterogeneity, hierarchy, and autonomy. First, we claim that heterogeneity (of disciplines, research questions, visions, social norms) is constitutive of the emergence of a new TSF. Second, the population of Synbio researchers is highly stratified; a core group of scientific entrepreneurs (incumbents and challengers) plays an active role in the process of emergence. Third, strategies for the control of external resources are crucial to the structuration of the field, which is mirrored by the prominent role of core-group members as boundary spanners. An original scientometric approach is used to create specific variables that allow us to investigate both network and field structural dynamics bridging qualitative and quantitative approaches.
Community by Template? Considering the Role of Templates for Enacting Membership in Digital Communities of Practice
Authors: Jarke Juliane
Published: March 2021

This chapter attends to how the concept of “communities of practice” (Lave and Wenger, Situated learning: Legitimate peripheral participation, learning in doing. Cambridge University Press, Cambridge, 1991) has been taken up by managers and policy makers in trans-local contexts. Although the concept was developed for co-located communities, it was transferred to distributed settings. In such settings, the sharing of practices is not necessarily active, and the performance of community not necessarily tied to their sharing. Some of the ambiguities of the original concept became problematic. The chapter is based on two vignettes that demonstrate how community is understood by policy makers and managers as a form of organisation that needs to be cultivated and coordinated. Continuing on the success of “communities of practice”, a focus of such striving became the sharing of experiences (and “good practices”) in order to foster community building. In a trans-local context, this meant—for the actors responsible for building community—a focus on how practices may be shared actively. One answer to this challenge was to describe local practices in standardised templates. However, different ways of organising the sharing of knowledge objects (e.g. who are the actors that define the structure of templates or how do they determine what counts as ‘good practice’) resulted in different forms of communality.
Constructing a universe for the setoid model
Authors: Altenkirch Thorsten , Boulier Simon , Kaposi Ambrus , Sattler Christian , Sestini Filippo
Published: March 2021

The setoid model is a model of intensional type theory that validates certain extensionality principles, like function extensionality and propositional extensionality, the latter being a limited form of univalence that equates logically equivalent propositions. The appeal of this model construction is that it can be constructed in a small, intensional, type theoretic metatheory, therefore giving a method to boostrap extensionality. The setoid model has been recently adapted into a formal system, namely Setoid Type Theory (SeTT). SeTT is an extension of intensional Martin-Löf type theory with constructs that give full access to the extensionality principles that hold in the setoid model.

Although already a rich theory as currently defined, SeTT currently lacks a way to internalize the notion of type beyond propositions, hence we want to extend SeTT with a universe of setoids. To this aim, we present the construction of a (non-univalent) universe of setoids within the setoid model, first as an inductive-recursive definition, which is then translated to an inductive-inductive definition and finally to an inductive family. These translations from more powerful definition schemas to simpler ones ensure that our construction can still be defined in a relatively small metatheory which includes a proof-irrelevant identity type with a strong transport rule.
Interpolation and Amalgamation for Arrays with MaxDiff
Authors: Ghilardi Silvio , Gianola Alessandro , Kapur Deepak
Published: March 2021

In this paper, the theory of McCarthy’s extensional arrays enriched with a maxdiff operation (this operation returns the biggest index where two given arrays differ) is proposed. It is known from the literature that a diff operation is required for the theory of arrays in order to enjoy the Craig interpolation property at the quantifier-free level. However, the diff operation introduced in the literature is merely instrumental to this purpose and has only a purely formal meaning (it is obtained from the Skolemization of the extensionality axiom). Our maxdiff operation significantly increases the level of expressivity; however, obtaining interpolation results for the resulting theory becomes a surprisingly hard task. We obtain such results via a thorough semantic analysis of the models of the theory and of their amalgamation properties. The results are modular with respect to the index theory and it is shown how to convert them into concrete interpolation algorithms via a hierarchical approach.
Nominal Equational Problems
Authors: Ayala-Rincón Mauricio , Fernández Maribel , Nantes-Sobrinho Daniele , Vale Deivid
Published: March 2021

We define nominal equational problems of the form $$\exists \overline{W} \forall \overline{Y} : P$$

∃

W

¯

∀

Y

¯

:
P

, where $$P$$
P
consists of conjunctions and disjunctions of equations $$s\approx _\alpha t$$

s

≈
α

t

, freshness constraints $$a\#t$$

a
#
t

and their negations: $$s \not \approx _\alpha t$$

s

≉
α

t

and "Equation missing", where $$a$$
a
is an atom and $$s, t$$

s
,
t

nominal terms. We give a general definition of solution and a set of simplification rules to compute solutions in the nominal ground term algebra. For the latter, we define notions of solved form from which solutions can be easily extracted and show that the simplification rules are sound, preserving, and complete. With a particular strategy for rule application, the simplification process terminates and thus specifies an algorithm to solve nominal equational problems. These results generalise previous results obtained by Comon and Lescanne for first-order languages to languages with binding operators. In particular, we show that the problem of deciding the validity of a first-order equational formula in a language with binding operators (i.e., validity modulo $$\alpha $$
α
-equality) is decidable.
A String Diagrammatic Axiomatisation of Finite-State Automata
Authors: Piedeleu Robin , Zanasi Fabio
Published: March 2021

We develop a fully diagrammatic approach to finite-state automata, based on reinterpreting their usual state-transition graphical representation as a two-dimensional syntax of string diagrams. In this setting, we are able to provide a complete equational theory for language equivalence, with two notable features. First, the proposed axiomatisation is finite— a result which is provably impossible for the one-dimensional syntax of regular expressions. Second, the Kleene star is a derived concept, as it can be decomposed into more primitive algebraic blocks.
Learning Pomset Automata
Authors: van Heerdt Gerco , Kappé Tobias , Rot Jurriaan , Silva Alexandra
Published: March 2021

We extend the$$\mathtt {L}^{\!\star }$$L⋆algorithm to learn bimonoids recognising pomset languages. We then identify a class of pomset automata that accepts precisely the class of pomset languages recognised by bimonoids and show how to convert between bimonoids and automata.
Fixpoint Theory – Upside Down
Authors: Baldan Paolo , Eggert Richard , König Barbara , Padoan Tommaso
Published: March 2021

Knaster-Tarski’s theorem, characterising the greatest fix- point of a monotone function over a complete lattice as the largest post-fixpoint, naturally leads to the so-called coinduction proof principle for showing that some element is below the greatest fixpoint (e.g., for providing bisimilarity witnesses). The dual principle, used for showing that an element is above the least fixpoint, is related to inductive invariants. In this paper we provide proof rules which are similar in spirit but for showing that an element is above the greatest fixpoint or, dually, below the least fixpoint. The theory is developed for non-expansive monotone functions on suitable lattices of the form$$\mathbb {M}^Y$$MY, whereYis a finite set and$$\mathbb {M}$$Man MV-algebra, and it is based on the construction of (finitary) approximations of the original functions. We show that our theory applies to a wide range of examples, including termination probabilities, behavioural distances for probabilistic automata and bisimilarity. Moreover it allows us to determine original algorithms for solving simple stochastic games.