Miracle-dz/UniFAR-FTUs huggingface dataset:
N6-Methyladenosine Methyltransferase METTL3 Promotes Angiogenesis and Atherosclerosis by Upregulating the JAK2/STAT3 Pathway via m6A Reader IGF2BP1

Atherosclerosis (AS) is a life-threatening vascular disease. RNA N6-methyladenosine (m6A) modification level is dysregulated in multiple pathophysiologic processes including AS. In this text, the roles and molecular mechanisms of m6A writer METTL3 in AS progression were explored in vitro and in vivo. In the present study, cell proliferative, migratory, and tube formation capacities were assessed through CCK-8, Transwell migration, and tube formation assays, respectively. RNA m6A level was examined through a commercial kit. RNA and protein levels of genes were measured through RT-qPCR and western blot assays, respectively. VEGF secretion level was tested through ELISA assay. JAK2 mRNA stability was detected through actinomycin D assay. The relationship of METTL3, IGF2BP1, and JAK2 was investigated through bioinformatics analysis, MeRIP, RIP, RNA pull-down, and luciferase reporter assays. An AS mouse model was established to examine the effect of METTL3 knockdown on AS development in vivo. The angiogenetic activity was examined through chick chorioallantoic membrane assay in vivo. The results showed that METTL3 was highly expressed in ox-LDL-induced dysregulated HUVECs. METTL3 knockdown inhibited cell proliferation, migration, tube formation, and VEGF expression/secretion in ox-LDL-treated HUVECs, hampered AS process in vivo, and prevented in vivo angiogenesis of developing embryos. METTL3 positively regulated JAK2 expression and JAK2/STAT3 pathway in an m6A dependent manner in HUVECs. IGF2BP1 positively regulated JAK2 expression through directly binding to an m6A site within JAK2 mRNA in HUVECs. METTL3 knockdown weakened the interaction of JAK2 and IGF2BP1. METTL3 exerted its functions through JAK2/STAT3 pathway. In conclusion, METTL3 knockdown prevented AS progression by inhibiting JAK2/STAT3 pathway via IGF2BP1.
Political economy of road maintenance: a utility diagnostic

ABSTRACT Sub-Saharan Africa requires US$30 billion annually for its infrastructure maintenance, with every dollar spent saving the economy about four times that. However, many governments still do not recognise the need for road maintenance, increasing vehicle operating costs – to more than 1% of GDP in some regions. Still, there are too few political economy diagnostics of this problem and policy responses aiming to ring-fence dedicated funds have had mixed results. This article proposes a diagnostic through which to understand the institutional root causes of the problem using the case of Moldova.
Avoidance of pseudogene interference in the detection of 3′ deletions in PMS2

Lynch syndrome is characterized by mutations in the mismatch repair genes MLH1, MSH2, MSH6, and PMS2. In PMS2, detection of mutations is confounded by numerous pseudogenes. Detection of 3′ deletions is particularly complicated by the pseudogene PMS2CL, which has strong similarity to PMS2 exons 9 and 11–15, due to extensive gene conversion. A newly designed multiplex ligation‐dependent probe amplification (MLPA) kit incorporates probes for variants found in both PMS2 and PMS2CL. This provides detection of deletions, but does not allow localization of deletions to the gene or pseudogene. To address this, we have developed a methodology incorporating reference samples with known copy numbers of variants, and paired MLPA results with sequencing of PMS2 and PMS2CL. We tested a subset of clinically indicated samples for which mutations were either unidentified or not fully characterized using existing methods. We identified eight unrelated patients with deletions encompassing exons 9–15, 11–15, 13–15, 14–15, and 15. By incorporating specific, characterized reference samples and sequencing the gene and pseudogene it is possible to identify deletions in this region of PMS2 and provide clinically relevant results. This methodology represents a significant advance in the diagnosis of patients with Lynch syndrome caused by PMS2 mutations. Hum Mutat 32:1063–1071, 2011. © 2011 Wiley‐Liss, Inc.
Actuator and sensor fault reconstruction for a class of uncertain linear systems

This paper considers the simultaneous actuator and sensor fault reconstruction problems for linear systems when the observer matching condition is not satisfied. A new augmented system is constructed and an auxiliary output vector is proposed so that the observer matching condition is satisfied. A high-order sliding mode observer is considered to obtain the exact estimates of both the auxiliary outputs and their derivatives. A kind of actuator and sensor fault reconstruction method is developed based on a reduced-order observer and the high-order sliding mode observer. Finally, a numerical simulation is given to illustrate the effectiveness of the proposed methods.
Weak Labeled Multi-Label Active Learning for Image Classification

In order to achieve better classification performance with even fewer labeled images, active learning is suitable for these situations. Several active learning methods have been proposed for multi-label image classification, but all of them assume that all training images with complete labels. However, as a matter of fact, it is very difficult to get complete labels for each example, especially when the size of labels in a multi-label domain is huge. Usually, only partial labels are available. This is one kind of "weak label" problems. This paper proposes an ingeniously solution to this "weak label" problem on multi-label active learning for image classification (called WLMAL). It explores label correlation on the weak label problem with the help of input features, and then utilizes label correlation to evaluate the informativeness of each example-label pair in a multi-label dataset for active sampling. Our experimental results on three real-world datasets show that our proposed approach WLMAL consistently outperforms existing approaches significantly.
The Effects of Differentially-Expressed Homeobox Family Genes on the Prognosis and HOXC6 on Immune Microenvironment Orchestration in Colorectal Cancer

Background The homeobox (HOX) gene family encodes highly conserved transcription factors, that play important roles in the morphogenesis and embryonic development of vertebrates. Mammals have four similar HOX gene clusters, HOXA, HOXB, HOXC, and HOXD, which are located on chromosomes 7, 17,12 and 2 and consist of 38 genes. Some of these genes were found to be significantly related to a variety of tumors; however, it remains unknown whether abnormal expression of the HOX gene family affects prognosis and the tumor microenvironment (TME) reshaping in colorectal cancer (CRC). Therefore, we conducted this systematic exploration to provide additional information for the above questions. Methods RNA sequencing data from The Cancer Genome Atlas (TCGA) and mRNA expression data from Gene Expression Omnibus (GEO) combined with online tumor analysis databases (UALCAN, TIMER, PrognoScan) were utilized to explore the relationship among abnormal expression of HOX family genes, prognosis and the tumor immune microenvironment in CRC. Results 1. Differential expression and prognosis analysis: 24 genes were significantly differentially expressed in CRC compared to adjacent normal tissues, and seven upregulated genes were significantly associated with poor survival. Among these seven genes, univariate and multivariate Cox regression analysis revealed that only high expression of HOXC6 significantly contributed to poor prognosis; 2. The influence of overexpressed HOXC6 on the pathway and TME: High HOXC6 expression was significantly related to the cytokine pathway and expression of T cell attraction chemokines, the infiltration ratio of immune cells, expression of immune checkpoint markers, tumor mutation burden (TMB) scores and microsatellite instability-high (MSI-H) scores; 3. Stratified analysis based on stages: In stage IV, HOXC6 overexpression had no significant impact on TMB, MSI-H, infiltration ratio of immune cells and response prediction of immune checkpoint blockers (ICBs), which contributed to significantly poor overall survival (OS). Conclusion Seven differentially expressed HOX family genes had significantly worse prognoses. Among them, overexpressed HOXC6 contributed the most to poor OS. High expression of HOXC6 was significantly associated with high immunogenicity in nonmetastatic CRC. Further research on HOXC6 is therefore worthwhile to provide potential alternatives in CRC immunotherapy.
Characterization of the Promoter and the Transcriptional Regulation of the Lipoxin A4 Receptor (FPR2/ALX) Gene in Human Monocytes and Macrophages

The lipoxin A4 receptor FPR2/ALX plays an important part in host defense and inflammation. The receptor binds structurally diverse agonistic ligands, which mainly regulate chemotaxis and activation of leukocytes. However, little is known about the promoter region of the FPR2/ALX gene and its transcriptional regulation in leukocytes. We identified two TATA-less promoter regions, separated by 224 bp, that drive the expression of FPR2/ALX in macrophages. Both promoter regions increased transcription in a reporter assay, and the basal transcription factors OCT1 and SP1 were shown to bind the first and the second promoter, respectively, and to transactivate transcription. Although monocytes expressed high levels of FPR2/ALX mRNA from the second promoter region, differentiation into macrophages abrogated FPR2/ALX expression. Stimulation of macrophages with a set of cytokines revealed that only IFN-γ and LPS increased FPR2/ALX expression from the first promoter to levels similar to those detected in monocytes. The upregulation by IFN-γ is in part mediated by the interaction of IFN regulatory factor 1 with an IFN-responsive sequence element transcription factor binding site located in the first promoter region of the FPR2/ALX gene. However, this upregulation on the mRNA level did not translate into FPR2/ALX protein expression in macrophages owing to reduced translation of the longer mRNA from the first promoter. In contrast, FPR2/ALX mRNA transcribed from the second promoter was translated into surface expression of FPR2/ALX in monocytes. These data support a model in which FPR2/ALX plays a role in chemotaxis and activation of monocytes; however, they also suggest that its function in resident tissue macrophages is limited.
Evaluación de eficiencia de cooperativas de ahorro y crédito en Ecuador: Aplicación del modelo Análisis Envolvente de Datos DEA

Uno de los pilares importantes del Sistema Financiero Ecuatoriano es el constituido por las Cooperativas de Ahorro y Crédito, debido a su amplio crecimiento obtenido en los últimos años y la gran cantidad de clientes que han logrado atraer. El objetivo principal de este estudio, es realizar un análisis sobre la Eficiencia Técnica de 18 Cooperativas de Ahorro y Crédito (COACs) consideradas en el “Segmento 1” del ranking de cooperativas ecuatorianas presentadas por la Superintendencia de Economía Popular y Solidaria (SEPS) en el periodo 2016; para el análisis utilizaremos un conjunto de datos financieros de cada cooperativa, correspondientes a un periodo de 10 años, 2007-2016. En este contexto hemos utilizado el modelo DEA (Data Envelopment Analysis) para determinar los ratios de eficiencia de cada cooperativa, obteniendo como resultado un promedio de 77,02 % de eficiencia en todo el período analizado, y resultando una sola cooperativa con el 100% de eficiencia.
Workplace gossip and frontline employees’ proactive service performance

ABSTRACT Managers are interested in promoting frontline employees’ proactive behavior because proactivity is crucial for organizational success. This study examined the link between perceived workplace gossip and employees’ (targets’) proactive service performance by focusing on the mediating role of employees’ harmonious passion and the moderating role of perceived job social support. Using time-lagged survey data from 218 supervisor-subordinate dyads in a commercial bank in China, we found that perceived workplace gossip negatively influences employees’ proactive service performance, and that this relationship is mediated by reduced harmonious passion. In addition, perceived job social support attenuates the negative relationship between perceived workplace gossip and harmonious passion, with harmonious passion having a mediating effect on the relationship between perceived workplace gossip and proactive service performance. These results provide new directions for understanding workplace gossip, harmonious passion, proactive service performance, and job social support. The theoretical and practical implications of our findings are discussed.
Differentiating between right-lateralised semantic dementia and behavioural-variant frontotemporal dementia: an examination of clinical characteristics and emotion processing

Background and purpose Right-lateralised semantic dementia (right SD) and behavioural-variant frontotemporal dementia (bvFTD) appear clinically similar, despite different patterns of underlying brain changes. This study aimed to elucidate distinguishing clinical and cognitive features in right SD versus bvFTD, emphasising emotion processing and its associated neural correlates. Methods 12 patients with right SD and 19 patients with bvFTD were recruited. Clinical features were documented. All patients were assessed on standardised neuropsychological tests and a facial emotion processing battery. Performance was compared to 20 age-matched and education-matched controls. Grey matter intensity was related to emotion processing performance using whole-brain voxel-based morphometry analysis. Results Patients with right SD exhibited disproportionate language dysfunction, prosopagnosia and a suggestion of increased obsessive personality/behavioural changes versus patients with bvFTD. In contrast, patients with bvFTD demonstrated pronounced deficits in attention/working memory, increased apathy and greater executive dysfunction, compared to patients with right SD. Decreased empathy, disinhibition and diet changes were common to both dementia subtypes. Emotion processing deficits were present in both FTD syndromes but were associated with divergent patterns of brain atrophy. In right SD, emotion processing dysfunction was associated with predominantly right medial and lateral temporal integrity, compared to mainly left temporal, inferior frontal and orbitofrontal and right frontal gyrus integrity in bvFTD. Conclusions This study demonstrates comparable deficits in facial emotion processing in right SD and bvFTD, in keeping with their similar clinical profiles. These deficits are attributable to divergent neural substrates in each patient group, namely, right lateralised regions in right SD, versus predominantly left lateralised regions in bvFTD.
Resting Energy Expenditure in Children Newly Diagnosed With Stage IV Neuroblastoma

Children with stage IV neuroblastoma (NBIV) are often malnourished at time of diagnosis, observed as high as 50%. The emphasis of this study was to determine whether an increased resting energy expenditure (REE) is a causative factor. Our hypothesis was that children diagnosed with NBIV have an increased REE, which normalizes with cancer treatment. Changes in nutritional status from time of diagnosis in response to nutritional support were examined. REE and nutritional evaluation were obtained three times: at diagnosis before starting treatment, where tumor burden is expected to be highest; after two courses of chemotherapy, where some response to treatment is expected; and after surgical excision of the primary tumor, where there was presumably minimal residual disease. Ten subjects completed the study. Results showed that REE was not increased, and there was no significant difference between phases (p = 0.29). Fifty percent of our subjects were malnourished at diagnosis. Because REE is not increased in NBIV, it is concluded that malnutrition seen in NBIV is not due to increased energy needs, but is likely due to decreased intake because of the intra-abdominal mass and malignant malaise.
Piper sarmentosum as an antioxidant on oxidative stress in human umbilical vein endothelial cells induced by hydrogen peroxide

Endothelial cell death due to increased reactive oxygen species (ROS) may contribute to the initial endothelial injury, which promotes atherosclerotic lesion formation. Piper sarmentosum (PS), a natural product, has been shown to have an antioxidant property, which is hypothesized to inhibit production of ROS and prevent cell injury. Thus, the present study was designed to determine the effects of PS on the hydrogen peroxide (H2O2)-induced oxidative cell damage in cultured human umbilical vein endothelial cells (HUVECs). In this experiment, HUVECs were obtained by collagenase perfusion of the large vein in the umbilical cord and cultured in medium M200 supplemented with low serum growth supplementation (LSGS). HUVECs were treated with various concentrations of H2O2 (0–1000 μmol/L) and it was observed that 180 μmol/L H2O2 reduced cell viability by 50% as denoted by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Using the above concentration as the positive control, the H2O2-induced HUVECs were concomitantly treated with various concentrations (100, 150, 250 and 300 μg/ml) of three different extracts (aqueous, methanol and hexane) of PS. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) levels showed a significant increase (P<0.05) in HUVECs compared to the negative control. However, PS extracts showed a protective effect on HUVECs from H2O2-induced cell apoptosis with a significant reduction in MDA, SOD, CAT and GPX levels (P<0.05). Furthermore, PS had exhibited ferric reducing antioxidant power with its high phenolic content. Hence, it was concluded that PS plays a beneficial role in reducing oxidative stress in H2O2-induced HUVECs.
A Speech Scrambler Using the Fast Fourier Transform Technique

This paper describes an analog speech scrambler using the FFT technique (FFT scrambler). The FFT scrambler provides highly secured scrambled signal by permuting a large number of FFT coefficients. Important items to be considered in the designing of the FFT scrambler are discussed, such as FFT frame length, permutation of FFT coefficients, and frame synchronization, in addition to the configuration of the experimental FFT scrambler. Possible causes for the degradation of the descrambled signal, such as transmission channel group delay and intersymbol interference, are also discussed, together with experimental results.
Unresponsiveness of hepatic nitrogen metabolism to glucagon infusion in patients with cirrhosis: Dependence on liver cell failure

Glucagon exerts an up‐regulatory effect on hepatic nitrogen metabolism in healthy subjects, but its potential role in the presence of liver failure is uncertain. The effects of glucagon on urea synthesis and hepatic nitrogen clearance during alanine infusion were studied in five control subjects and six cirrhotic patients in paired experiments at spontaneous glucagon concentrations and at high physiological glucagon levels (≈ 300 to 500 pmol ˙ L−1) induced by a 7.5‐hr continuous glucagon infusion. In all experiments the urea nitrogen synthesis rate increased linearly with increasing α‐amino‐nitrogen concentrations. At spontaneous glucagon concentrations the dynamics of α‐amino nitrogen to urea nitrogen conversion (functional hepatic nitrogen clearance) were significantly reduced in cirrhosis (23.2 ± 6.7 L ˙ hr−1 vs. 35.3 ± 8.0 L ˙ hr−1, p < 0.05) in relation to decreased liver function. Glucagon superinfusion caused a 63% increase in the dynamics of the process in controls (57.7 ± 11.0 L ˙ hr−1; p vs. spontaneous glucagon, p < 0.01), whereas in cirrhosis it increased on average by only 15% (26.7 ± 10.7; p = NS). The glucagon‐induced change in functional hepatic nitrogen clearance significantly correlated with galactose elimination capacity and antipyrine clearance (r = 0.905 and 0.964, respectively). Glucagon, in high physiological concentrations achieved with glucagon infusion, does not produce significant effects on hepatic nitrogen metabolism in cirrhosis. The reduced sensitivity of the cirrhotic liver to glucagon seems to be dependent on decreased hepatocellular function. These data do not support the role of glucagon as a “catabolic” hormone in cirrhosis. (HEPATOLOGY 1993;18:28–35).
Newborn sickle cell disease screening: the Jamaican experience (1995–2006)

Objectives: The aim of this study was to evaluate the existing newborn sickle haemoglobinopathy screening programme in Jamaica. Methods: A retrospective analysis of infants screened during the period 8 November 1995 to 22 July 2006 was performed. Patient data for analyses was restricted to patients with homozygous (Hb SS) sickle cell disease. Published data from the Jamaican Sickle Cell Cohort Study was used to make comparisons with the study sample. Results: The study sample consisted of 435 patients with Hb SS disease. Acute chest syndrome was the most common clinical (non-death) event accounting for ∼50% of all events. Acute splenic sequestration, no longer a significant cause of mortality, was responsible for ∼32% of clinical events. Seven deaths (1.8%) occurred during the study period compared with 17.6% to the same age in the Jamaican Sickle Cell Cohort Study. There was a lower proportion of hospital admissions and episodes of serious illness in the study group compared with controls. Conclusions: Survival estimates for the study sample showed improvement compared with the Jamaican Sickle Cell Cohort Study. This study continues to demonstrate the benefits of, and as such shows support for, newborn screening and early interventions in sickle cell disease. In addition, it highlights some of the areas for continued focus and research development. Although the current system is providing an essential and beneficial service, the study emphasizes the need for newborn screening programmes to be comprehensive care systems to be fully effective.
Effect of Soil Ammonium Concentration on N2O Release and on the Community Structure of Ammonia Oxidizers and Denitrifiers

ABSTRACT The effect of ammonium addition (6.5, 58, and 395 μg of NH4+-N g [dry weight] of soil−1) on soil microbial communities was explored. For medium and high ammonium concentrations, increased N2O release rates and a shift toward a higher contribution of nitrification to N2O release occurred after incubation for 5 days at 4°C. Communities of ammonia oxidizers were assayed after 4 weeks of incubation by denaturant gradient gel electrophoresis (DGGE) of the amoA gene coding for the small subunit of ammonia monooxygenase. The DGGE fingerprints were invariably the same whether the soil was untreated or incubated with low, medium, or high ammonium concentrations. Phylogenetic analysis of cloned PCR products from excised DGGE bands detected amoA sequences which probably belonged to Nitrosospira 16S rRNA clusters 3 and 4. Additional clones clustered with Nitrosospira sp. strains Ka3 and Ka4 and within an amoA cluster from unknown species. A Nitrosomonas-like amoA gene was detected in only one clone. In agreement with the amoA results, community profiles of total bacteria analyzed by terminal restriction fragment length polymorphism (T-RFLP) showed only minor differences. However, a community shift occurred for denitrifier populations based on T-RFLP analysis of nirK genes encoding copper-containing nitrite reductase with incubation at medium and high ammonia concentrations. Major terminal restriction fragments observed in environmental samples were further described by correspondence to cloned nirK genes from the same soil. Phylogenetic analysis grouped these clones into clusters of soil nirK genes. However, some clones were also closely related to genes from known denitrifiers. The shift in the denitrifier community was probably the consequence of the increased supply of oxidized nitrogen through nitrification. Nitrification activity increased upon addition of ammonium, but the community structure of ammonium oxidizers did not change.