Is hyperuricemia an independent risk factor for new-onset chronic kidney disease?: a systematic review and meta-analysis based on observational cohort studies

This article discusses the role of interrogation in intelligence during the Second World War, and it focuses on the importance of culture in the collection of Human Intelligence in the European theatre of operation. It argues that cultural issues, including but not limited to language knowledge, provided an added value to interrogation, interviewing and questioning during and after the Second World War, for example through the employment of native speakers, in particular former refugees and enemy aliens. The article also highlights some of the flaws involved in this process, which led to bad prisoner handling and therefore bad intelligence collection. It also tries to complement archival sources with personal accounts and oral histories in order to achieve a deeper understanding of the role of the human being in the collection of intelligence through interrogation and questioning

The Information Role of Earnings Conference Call Tone: Evidence from Stock Price Crash Risk

This paper investigates whether and how the disclosure tone of earnings conference calls predicts future stock price crash risk. Using US public firms’ conference call transcripts from 2010 to 2015, we find that firms with less optimistic tone of year-end conference calls experience higher stock price crash risk in the following year. Additional analyses reveal that the predictive power of tone is more pronounced among firms with better information environment and lower managerial equity incentives, suggesting that extrinsic motivations for truthful disclosure partially explain the predictive power of conference call tone. Our results shed light on the long-term information role of conference call tone by exploring the setting of extreme future downside risk, when managers have conflicting incentives either to unethically manipulate disclosure tone to hide bad news or to engage in ethical and truthful communication

The information role of earnings conference call tone : evidence from stock price crash risk

This paper investigates whether and how the disclosure tone of earnings conference calls predicts future stock price crash risk. Using US public firms’ conference call transcripts from 2010 to 2015, we find that firms with less optimistic tone of year-end conference calls experience higher stock price crash risk in the following year. Additional analyses reveal that the predictive power of tone is more pronounced among firms with better information environment and lower managerial equity incentives, suggesting that extrinsic motivations for truthful disclosure partially explain the predictive power of conference call tone. Our results shed light on the long-term information role of conference call tone by exploring the setting of extreme future downside risk, when managers have conflicting incentives either to unethically manipulate disclosure tone to hide bad news or to engage in ethical and truthful communication

Perancangan Sistem Otomatis Update pada Aplikasi Desktop Abios

Unlike web applications easier to update the latest version, desktop applications more difficult and must involve the user in doing so. It is caused by a desktop application is an application that is installed in the computer user. The purpose of this research is to design an automatic system updates on a desktop application, an example case: Application Binus International Operational Support (ABIOS). This research used literature study and system design. In desktop applications, often there is update the latest applications that are not known to the user who sometimes fatal and disrupt business operations. Generally, developer will inform the changes version to user that they can update the application. In an update of applications, should be done by the system automatically, not manually by users. Once in a while, the user background is not from computer base. After doing the research, it can be concluded that the system automatically updates the application has benefits to users in obtaining information regarding the latest version, and can assist in automatically update the latest application is based on computerization. For further development of this system is expected to operate on multi platforms and or mobile applications

17β-Estradiol Enhances the Response of Plasmacytoid Dendritic Cell to CpG

Gender differences in immune capabilities suggest that sex hormones such as estrogens were involved in the regulation of the immunocompetence. Numerous studies also suggest that plasmacytoid dendritic cells (PDCs) play a pathogenic role in SLE. However, it is unclear whether estrogen can modulate the function of PDCs to influence the development of SLE. In the present study, PDCs from murine spleens were treated with 17β-estradiol (E2) and CpG respectively or both in vitro, then cell viability, costimulatory molecule expression, cytokine secretion of PDCs, as well as stimulatory capacity of PDCs to B cells were analyzed. Results showed that E2 and CpG increased the cell viability and costimulatory molecule expression on PDCs synergistically. Moreover, the intracellular and extracellular secretion of IFN-α was increased by E2 or E2 plus CpG. In addition, E2 and CpG also increased the stimulatory capacity of PDCs to B cells, and the viability of B cells was decreased after neutralizing IFN-α significantly. In the experiments in vivo, mice received daily s.c. injections of E2 and CpG respectively or both, then we found that the plasma concentration of IgM were elevated by E2 and CpG synergistically and the expression of IFN-α/β in spleens were noticeably increased by CpG plus E2 compared with the treatment of E2 or CpG only. This study indicates that E2 could exacerbate PDCs' activation with CpG, which further activates B cells to upregulate susceptibility to autoantigens. IFN-α plays an important role in the stimulatory effect of PDCs on B cells. E2 stimulation of IFN-α production may result in female prevalence in autoimmune diseases such as SLE through activation of PDCs. This study provides novel evidence of relationship between estrogen and SLE and also sheds light on gender biases among SLE patients

A network‐based variable selection approach for identification of modules and biomarker genes associated with end‐stage kidney disease

AimsIntervention for end‐stage kidney disease (ESKD), which is associated with adverse prognoses and major economic burdens, is challenging due to its complex pathogenesis. The study was performed to identify biomarker genes and molecular mechanisms for ESKD by bioinformatics approach.MethodsUsing the Gene Expression Omnibus dataset GSE37171, this study identified pathways and genomic biomarkers associated with ESKD via a multi‐stage knowledge discovery process, including identification of modules of genes by weighted gene co‐expression network analysis, discovery of important involved pathways by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, selection of differentially expressed genes by the empirical Bayes method, and screening biomarker genes by the least absolute shrinkage and selection operator (Lasso) logistic regression. The results were validated using GSE70528, an independent testing dataset.ResultsThree clinically important gene modules associated with ESKD, were identified by weighted gene co‐expression network analysis. Within these modules, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed important biological pathways involved in ESKD, including transforming growth factor‐β and Wnt signalling, RNA‐splicing, autophagy and chromatin and histone modification. Furthermore, Lasso logistic regression was conducted to identify five final genes, namely, CNOT8, MST4, PPP2CB, PCSK7 and RBBP4 that are differentially expressed and associated with ESKD. The accuracy of the final model in distinguishing the ESKD cases and controls was 96.8% and 91.7% in the training and validation datasets, respectively.ConclusionNetwork‐based variable selection approaches can identify biological pathways and biomarker genes associated with ESKD. The findings may inform more in‐depth follow‐up research and effective therapy.SUMMARY AT A GLANCEThis gene–gene network analysis to identify genes associated with end‐stage renal disease is an important step, albeit early, towards the discovery of biomarkers using peripheral blood cells. The findings also provide insight on disease pathophysiology at the molecular level, and hence therapeutic targets for future research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162799/2/nep13655.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162799/1/nep13655_am.pd

<i>Drosophila</i> carrying epilepsy-associated variants in the vitamin B6 metabolism gene PNPO display allele- and diet-dependent phenotypes

Pyridox(am)ine 5′-phosphate oxidase (PNPO) catalyzes the rate-limiting step in the synthesis of pyridoxal 5′-phosphate (PLP), the active form of vitamin B6 required for the synthesis of neurotransmitters gamma-aminobutyric acid (GABA) and the monoamines. Pathogenic variants in PNPO have been increasingly identified in patients with neonatal epileptic encephalopathy and early-onset epilepsy. These patients often exhibit different types of seizures and variable comorbidities. Recently, the PNPO gene has also been implicated in epilepsy in adults. It is unclear how these phenotypic variations are linked to specific PNPO alleles and to what degree diet can modify their expression. Using CRISPR-Cas9, we generated four knock-in Drosophila alleles, hWT, hR116Q, hD33V, and hR95H, in which the endogenous Drosophila PNPO was replaced by wild-type human PNPO complementary DNA (cDNA) and three epilepsy-associated variants. We found that these knock-in flies exhibited a wide range of phenotypes, including developmental impairments, abnormal locomotor activities, spontaneous seizures, and shortened life span. These phenotypes are allele dependent, varying with the known biochemical severity of these mutations and our characterized molecular defects. We also showed that diet treatments further diversified the phenotypes among alleles, and PLP supplementation at larval and adult stages prevented developmental impairments and seizures in adult flies, respectively. Furthermore, we found that hR95H had a significant dominant-negative effect, rendering heterozygous flies susceptible to seizures and premature death. Together, these results provide biological bases for the various phenotypes resulting from multifunction of PNPO, specific molecular and/or genetic properties of each PNPO variant, and differential allele–diet interactions

Metformin suppresses retinal angiogenesis and inflammation in vitro and in vivo

The oral anti-diabetic drug metformin has been found to reduce cardiovascular complications independent of glycemic control in diabetic patients. However, its role in diabetic retinal microvascular complications is not clear. This study is to investigate the effects of metformin on retinal vascular endothelium and its possible mechanisms, regarding two major pathogenic features of diabetic retinopathy: angiogenesis and inflammation. In human retinal vascular endothelial cell culture, metformin inhibited various steps of angiogenesis including endothelial cell proliferation, migration, and tube formation in a dose-dependent manner. Its anti-angiogenic activity was confirmed in vivo that metformin significantly reduced spontaneous intraretinal neovascularization in a very-low-density lipoprotein receptor knockout mutant mouse (p

Status and future of the soft X-ray free-electron laser beamline at the SHINE

The Shanghai High repetition rate XFEL and Extreme light facility (SHINE) is under construction and aims at generating X-rays between 0.4 and 25 keV with three FEL beamlines at repetition rates of up to 1 MHz. The soft X-ray FEL beamline, FEL-II, will be ready for commissioning in 2025. It is designed to cover the photon energy from 0.4 to 3 keV, in which the baselines of the FEL operation modes are self-amplified spontaneous emission (SASE), self-seeding, echo-enabled harmonic generation (EEHG), and polarization control. Therefore, a high repetition-rate external seed laser, large period length modulator, soft X-ray monochromator, planar undulator, and elliptically polarized undulator have been adopted in the FEL-II beamline. Several potentials such as an ultra-short pulse mode and a multi-color mode are also foreseeable without significant equipment changes in the follow-up operation. A dual-period undulator design is suggested for the echo-enabled harmonic generation (EEHG) commissioning, and it has great potential to break through the unreachable energy of the fully coherent X-ray in the future. The FEL-II beamline will deliver SASE radiation and fully coherent radiation in all the wavelengths of interest