On the Pseudo Smarandache function and its two conjectures

The main purpose of this paper is using the elementary method to study the properties of the Pseudo-Smarandache function Z(n), and solve two conjectures posed by Kenichiro Kashihara in reference

A Genetic Analysis of the Lysine Demethylase KDM2 Mutations in Drosophila Melanogaster

Post-translational modification of histones play essential roles in the transcriptional regulation of genes in eukaryotes. Methylation on basic residues of histones is regulated by histone methyltransferases and histone demethylases, and misregulation of these enzymes has been linked to a range of diseases such as cancer. Histone lysine demethylase 2 (KDM2) family proteins have been shown to either promote or suppress tumorigenesis in different human malignancies. However, the roles and regulation of KDM2 in development are poorly understood, and the exact roles of KDM2 in regulating demethylation remain controversial. Since KDM2 proteins are highly conserved in multicellular animals, we analyzed the KDM2 ortholog in Drosophila. We have observed that dKDM2 is a nuclear protein and its level fluctuates during fly development. We generated three deficiency lines that disrupt the dKdm2 locus, and together with 10 transposon insertion lines within the dKdm2 locus, we characterized the developmental defects of these alleles. The alleles of dKdm2 define three phenotypic classes, and the intragenic complementation observed among these alleles and our subsequent analyses suggest that dKDM2 is not required for viability. In addition, loss of dKDM2 appears to have rather weak effects on histone H3 lysine 36 and 4 methylation (H3K36me and H3K4me) in the third instar wandering larvae, and we observed no effect on methylation of H3K9me2, H3K27me2 and H3K27me3 in dKdm2 mutants. Taken together, these genetic, molecular and biochemical analyses suggest that dKDM2 is not required for viability of flies, indicating that dKdm2 is likely redundant with other histone lysine demethylases in regulating normal development in Drosophila

In Vivo Regulation of E2F1 by Polycomb Group Genes in Drosophila

The E2F transcription factors are important regulators of the cell cycle whose function is commonly misregulated in cancer. To identify novel regulators of E2F1 activity in vivo, we used Drosophila to conduct genetic screens. For this, we generated transgenic lines that allow the tissue-specific depletion of dE2F1 by RNAi. Expression of these transgenes using Gal4 drivers in the eyes and wings generated reliable and modifiable phenotypes. We then conducted genetic screens testing the capacity of Exelixis deficiencies to modify these E2F1-RNAi phenotypes. From these screens, we identified mutant alleles of Suppressor of zeste 2 [Su(z)2] and multiple Polycomb group genes as strong suppressors of the E2F1-RNA interference phenotypes. In validation of our genetic data, we find that depleting Su(z)2 in cultured Drosophila cells restores the cell-proliferation defects caused by reduction of dE2F1 by elevating the level of dE2f1. Furthermore, analyses of methylation status of histone H3 lysine 27 (H3K27me) from the published modENCODE data sets suggest that the genomic regions harboring dE2f1 gene and certain dE2f1 target genes display H3K27me during development and in several Drosophila cell lines. These in vivo observations suggest that the Polycomb group may regulate cell proliferation by repressing the transcription of dE2f1 and certain dE2F1 target genes. This mechanism may play an important role in coordinating cellular differentiation and proliferation during Drosophila development

STEM teaching for the Internet of Things maker course: a teaching model based on the iterative loop.

As the key technology for 5G applications in the future, the Internet of Things (IoT) is developing rapidly, and the demand for the cultivation of engineering talents in the IoT is also expanding. The rise of maker education has brought new teaching inspiration for cultivating innovative technical talents in the IoT. In the IoT maker course, teaching problems include the lack of adequate teaching models, emphasis on products but less emphasis on theory, and letting students imitate practice. Focusing on these problems, this paper proposes a new Science, Technology, Engineering, and Mathematics (STEM) teaching model called Propose, Guide, Design, Comment, Implement, Display and Evaluate (PGDCIDE) for the IoT maker course. The PGDCIDE teaching model is based on STEM teaching and Kolodner's design-based scientific inquiry learning cycle model, and realizes the combination of "theory, practice, and innovation." Finally, this paper designs the IoT maker course to practice the PGDCIDE model. The practical results indicate that students significantly improved their emotional level, knowledge level, and innovation level after studying the course. Therefore, the PGDCIDE teaching model proposed in this paper can improve the effectiveness of the IoT maker course teaching and is conducive to the cultivation of students' sustainable ability in engineering education. It has reference significance for the application of maker courses in engineering education practice

Risk and prognosis of second cutaneous melanoma after radiotherapy for breast cancer: A population-based analysis

Radiation therapy (RT), a primary treatment for breast cancer (BC), may be associated with increased non-BC tumor risk. We aimed to examine second cutaneous melanoma (SCM) risk in BC patients who underwent RT and to assess their survival outcomes. Data from 520,977 BC patients diagnosed between 1973–2018 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Cumulative SCM incidence was estimated using the Fine–Gray competing risk model. Poisson regression analysis was conducted to calculate the standardized incidence ratio (SIR) and estimate the SCM relative risk in patients who underwent RT compared to those who did not. Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan‒Meier method. Among the 520,977 BC patients, 243,676 (46.8%) underwent surgery and RT, while 277,301 (53.2%) only underwent surgery. Our results suggest that BC patients receiving RT had a higher SCM risk than those who did not (hazard ratio [HR] 1.40; 95% confidence interval [CI] 1.30-1.51; P < 0.001). SCM incidence was also higher in BC patients treated with RT than in the general US population (SIR 1.12; 95% CI 1.05-1.19; P < 0.05). However, SCM patients who received RT had a significantly higher 10-year survival rate than those who did not receive RT (14.90% vs 5.94%; P < 0.001). No significant difference was found in 10-year OS or 5-year CSS between SCM following RT and only primary cutaneous melanoma (OPCM), but SCM patients who did not receive RT had a significantly lower 10-year OS, with no significant difference in CSS. This study suggests an increased SCM likelihood in BC patients due to RT, although the overall risk is minimal

Insights into charge carrier dynamics in organo-metal halide perovskites: From neat films to solar cells

Organo-metal halide perovskites have recently obtained world-wide attention as promising solar cell materials. They have broad and strong light absorption along with excellent carrier transport properties which partially explain their record power conversion efficiencies above 22%. However, the basic understanding of the underlying physical mechanisms is still limited and there remain large discrepancies among reported transport characteristics of perovskite materials. Notably, the carrier mobility of perovskite samples either in thin films or within solar cells obtained using different techniques can vary by up to 7-8 orders of magnitude. This tutorial review aims to offer insights into the scope, advantages, limitations and latest developments of the techniques that have been applied for studying charge carrier dynamics in perovskites. We summarize a comprehensive set of measurements including (1) time-resolved laser spectroscopies (transient absorption, time-resolved photoluminescence, terahertz spectroscopy and microwave conductivity); (2) electrical transient techniques (charge extraction by linearly increasing voltage and time-of-flight); and (3) steady-state methods (field-effect transistor, Hall effect and space charge limited current). Firstly, the basics of the above measurements are described. We then comparatively summarize the charge carrier characteristics of perovskite-based neat films, bilayer films and solar cells. Finally, we compare the different approaches in evaluating the key parameters of transport dynamics and unravel the reasons for the large discrepancies among these methods. We anticipate that this tutorial review will serve as the entry point for understanding the experimental results from the above techniques and provide insights into charge carrier dynamics in perovskite materials and devices. 1 2017 The Royal Society of Chemistry.Z. L. thanks the support from the National Natural Science Foundation of China (NSFC) under grant no. 51473036. K. Z. and T. P. acknowledges the support from the Swedish Research Council, the KAW Foundation, the NPRP grant #NPRP7-227-1-034 obtained from the Qatar National Research Fund (a member of the Qatar Foundation), and the STINT grant #CH2015-6232 from the Swedish Foundation for International Cooperation in Research and Higher Education.Scopu

Modified nusinersen intrathecal injection method: inclusion of a septal needle-free closed infusion connector

ObjectiveNusinersen, an extremely expensive biologic drug (around 100,000 US$ per dose) that needs to be administered intrathecally, is approved for the treatment of 5q-spinal muscular atrophy (SMA). Because of the low muscle tone of the back muscles of pediatric SMA patients, especially type 1 SMA patients, the safe, effective, and fast execution of sheath injection is needed. Therefore, a modified intrathecal injection method was developed accordingly. This paper aims to describe the applicability and safety of this modified method.MethodsThe modified intrathecal injection method (MIIM) mainly includes a septal needle-free closed infusion connector between the lumbar puncture needle and the syringe, besides the procedures of routine lumbar puncture. Its applicability and safety were evaluated through clinical observation.ResultsA total of 92 children with SMA have successfully received nusinersen treatment at our hospital using the modified method since 2019 without obvious adverse events related to the modified injection method. Based on the clinical feedback of operators, the advantages of the modified method include successfully injecting the total dose of nusinersen with constant injection rate and a more stable fixation of the puncture needle, as well as making the operator more relaxed. However, compared with the routine method, the procedure of the modified method has additional steps.ConclusionThe modified intrathecal injection method is an effective and safe method to inject nusinersen when weighing the pros and cons, and it may also be used for administering intrathecal injections of other expensive medicines or for patients with other strict requirements for intrathecal injection

Autistic clinical profiles, age at first concern, and diagnosis among children with autism spectrum disorder

BackgroundTo explore the relationship between autistic clinical profiles and age at first concern and diagnosis among children with autism spectrum disorder. The clinical profiles included the severity of autism, cognition, adaptability, language development, and regression.MethodsThe multivariate linear regression model was used to examine the association of diagnostic age and first-concern age with autistic clinical profiles and with further stratification analysis.ResultsA total of 801 autistic children were included. Language delay and regression were associated with earlier diagnostic age (language delay: crudeβ: −0.80, 95%CI%: −0.92–−0.68; regression: crudeβ: −0.21, 95%CI%: −0.43–−0.00) and the age of first concern of autistic children (language delay: crudeβ: −0.55, 95%CI%: −0.65–−0.45; regression: crudeβ: −0.17, 95%CI%: −0.34–−0.00). After stratification by sex, language delay tended to be more associated with the earlier diagnostic age among boys (crudeβ: −0.85, 95%CI%: −0.98–−0.72) than among girls (crudeβ: −0.46, 95%CI%: −0.77–−0.16). After stratification by maternal education level or family income level, language delay was most associated with the earlier diagnostic age in autistic children from families with higher socioeconomic levels.ConclusionLanguage delay, rather than other symptoms, promoted an earlier diagnostic age. Among male autistic children or children from families with higher socioeconomic levels, language delay was most significantly associated with an earlier age of diagnosis. Cognitive delay, or adaptive delay, was associated with a later age at diagnosis and presented only in autistic children from families with lower socioeconomic levels. There may be sex or socioeconomic inequality in the diagnostic age for autistic children. More publicity and public education about the diversity of autistic symptoms are urgently needed in the future, especially for low-socioeconomic families

The Lysine Demethylase dKDM2 Is Non-essential for Viability, but Regulates Circadian Rhythms in Drosophila

Post-translational modification of histones, such as histone methylation controlled by specific methyltransferases and demethylases, play critical roles in modulating chromatin dynamics and transcription in eukaryotes. Misregulation of histone methylation can lead to aberrant gene expression, thereby contributing to abnormal development and diseases such as cancer. As such, the mammalian lysine-specific demethylase 2 (KDM2) homologs, KDM2A and KDM2B, are either oncogenic or tumor suppressive depending on specific pathological contexts. However, the role of KDM2 proteins during development remains poorly understood. Unlike vertebrates, Drosophila has only one KDM2 homolog (dKDM2), but its functions in vivo remain elusive due to the complexities of the existing mutant alleles. To address this problem, we have generated two dKdm2 null alleles using the CRISPR/Cas9 technique. These dKdm2 homozygous mutants are fully viable and fertile, with no developmental defects observed under laboratory conditions. However, the dKdm2 null mutant adults display defects in circadian rhythms. Most of the dKdm2 mutants become arrhythmic under constant darkness, while the circadian period of the rhythmic mutant flies is approximately 1 h shorter than the control. Interestingly, lengthened circadian periods are observed when dKDM2 is overexpressed in circadian pacemaker neurons. Taken together, these results demonstrate that dKdm2 is not essential for viability; instead, dKDM2 protein plays important roles in regulating circadian rhythms in Drosophila. Further analyses of the molecular mechanisms of dKDM2 and its orthologs in vertebrates regarding the regulation of circadian rhythms will advance our understanding of the epigenetic regulations of circadian clocks